ACADIA Pharmaceuticals Inc (ACAD) 2010 Q2 法說會逐字稿

Good day ladies and gentlemen. Welcome to ACADIA Pharmaceuticals second quarter 2010 financial results conference call. I'll be your coordinator for today. At this time, all participants are in listen-only mode. We will be facilitating a question-answer session toward 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.

Good afternoon and welcome to ACADIA Pharmaceuticals second quarter 2010 financial results conference call. This call is being recorded. An archived copy will be available on our website at www.acadia-pharm.com through August 23, 2010. Also joining the call from ACADIA today is Dr. Uli Hacksell, our Chief Executive Officer and Dr. Roger Mills, our Executive Vice President of Development. Uli will begin the call today by updating you on the progress we have made in executing our strategy. I will then briefly comment on our financial results for the second quarter. Following these remarks, Roger and Uli will provide you with an update on our development programs and we will then open the floor to 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 and our partner's research and development programs and plans, including the timing and results of clinical trials, potential payments pursuant to our collaboration agreements, the benefits to be derived from our product candidates and our future expenses, cash position and financial performance. These forward-looking statements are based on current information 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 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, 2009 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, our Chief Executive Officer.

Thank you, Tom. Let me take this opportunity to thank all of you for joining us on today's conference call. During the first half of 2010, we focused on executing our broad development strategy with pimavanserin, together with our partner Biovail. First we finalized preparations and recently initiated our new Phase IIl in Parkinson's disease psychosis or PDP which we refer to as the -020 Study. This Study build on the signals of antipsychotic efficacy observed in our previous PDP trials and gives us a refined study design that we expect will enhance the ability to demonstrate the efficacy of pimavanserin in PDP. Second, we continued with our preparations for a Phase II feasibility study with pimavanserin, as a treatment for Alzheimer's disease psychosis or ADP and we remain on track to initiate this study late this quarter. Third, Biovail continued with their planning for a Phase III trial with pimavanserin as a co-therapy in combination with risperidone to treat schizophrenia.

Our strategy is design to leverage the clinical potential of pimavanserin in these three indications with large medical needs and to position the parties to maximize the commercial potential of this product in North America. In addition to pimavanserin, we have two clinical programs in the areas of chronic pain and glaucoma, in collaboration with Allergan. The R&IND-track development with a product candidate for schizophrenia to our collaboration with Meiji Seika. We believe that our focus on this portfolio of our foremost advanced product candidates, led by a market faceted development program with pimavanserin firmly positions ACADIA with multiple product and commercial opportunities and significant growth potential. Let me now turn the call over to Tom, to comment on our second quarter financial results.

Thank you, Uli. I am pleased to note that we are continuing to see the desired effects of the cost saving measures we implemented last October, to streamline our organization and extend our cash runway. We reported a net loss of $4.3 million or $0.11 per common share for the second quarter of 2010, compared to a net loss of $12.7 million or $0.34 per common share for the comparable quarter of 2009. Our revenues increased to $2.3 million for the second quarter from $1.8 million in the comparable quarter of 2009, primarily due to increased revenues from our collaboration with Biovail. Our research and development expenses decrease to $5 million for the second quarter from $12 million for the second quarter of 2009. This decrease was largely driven by lower external service costs associated with our Phase III PDP trials as well as cost savings resulting from our October 2009 restructuring. Our general and administrative expenses decreased to $1.6 million for the second quarter, from $2.7 million in the comparable quarter of 2009, reflecting cost savings in both internal and external expenses.

Let me now turn to the funding responsibilities for the various pimavanserin programs being pursued under our collaboration with Biovail and the expected impact on our future of financial results. Under the agreement, Biovail is responsible for the costs associated with the development, manufacturing and commercialization of pimavanserin in North America for all indications, with the exception of specified PDP Study costs and the ADP Phase II feasibility study which will be funded by ACADIA. Beginning with the PDP indication Biovail is responsible for funding the new -020 Phase III PDP trial which was recently initiated. However, since we are managing this trial, we will incur the related expenses on our books and be reimbursed for these external clinical costs periodically by Biovail. We anticipate that our external R&D costs will begin to increase in the second half of 2010, as we progress with this trial. We estimate that the -020 Study will cost in the range of $10 million to $12 million and that the expenses are expected to be incurred over approximately a two year period.

While there is not expected to be any overall impact on our cash as a result of the reimbursement of the -020 external clinical costs by Biovail our future financial results may be impacted in three ways. First, fluctuations will occur period to period, due to the timing of expenses incurred, and reimbursements received. Second, because we recognize revenues from the reimbursement of development costs, using a contingency adjusted performance model over the expected period of performance of our collaboration, revenues will not match the related expenses incurred in a given period. And finally, under the terms of our collaboration, if the -020 Study does not meet its primarily end point, we would be required to reimburse Biovail 0.5 of the study costs. As a result we are deferring revenue recognition of 0.5 of the reimbursements received for the -020 Study until the outcome is determined. When it comes to the ADP indications ACADIA is responsible for funding the initial Phase II feasibility study in this program. However, if this study is successful, Biovail will reimburse us 100% of the costs of the study. Biovail will then be responsible for any remaining development costs for ADP that may arise, following the initial trial. Finally, with regard to the schizophrenia indication, Biovail is responsible for managing and funding this program. Let me close by reviewing our cash position, and updated guidance. We ended the second quarter with $34.3 million in cash and investment securities. We continue to expect that our existing cash resources and anticipated payments from our collaborations will be sufficient to fund our operations through the end of 2011. I'll now turn the call back over to Uli.

Thank you, Tom. We remain focused on our four most advanced product candidates, which are pimavanserin, in collaboration with Biovail, as well as two important clinical stage product candidates that are fully funded by Allergan and a program in IND-track development in collaboration with Meiji Seika. Our remarks today will focus on our development programs with pimavanserin. Let me start by asking Roger to provide you with an update on our Phase III program with pimavanserin in PDP.

Thank you, Uli. Good afternoon, as Uli mentioned earlier our recent efforts have focused on -020 Study, our new Phase III trial with pimavanserin in PDP, which we recently initiated. This multi-center, double blind placebo controlled study is designed to evaluate the efficacy, tolerability and safety of pimavanserin in patients with PDP It builds on the signals of antipsychotic efficacy observed in our two previous Phase III PDP trials, the -012 and -014 Studies. And incorporates several design enhancements that we believe will help mitigate placebo response, reduce variability, and enhance sensitivity, in measuring the efficacy of pimavanserin in PDP. These design and enhancements include testing a 40-milligram dose of pimavanserin versus placebo, in a one-to-one randomization in contrast to our previous studies, which tested two doses of pimavanserin versus placebo. Focusing on the study in North America, where we employ centralized ratings to assess the primary end point in contrast our previous studies were international with only about half of the patients from North America. Refining the primary end point of antipsychotic efficacy, using a group of nine items, from the hallucinations and delusions domains of the scale for the assessment of positive symptoms SAPS, that are most reflective of the expression of PDP symptomatology.

Our previous study uses total of 20 items from the SAPS as a primary end point. The other 11 items not contributing to the characterization of the expression of psychosis in these patients. Implementing other refinements, including fear ratings and assessments. The refinement in the SAPS end point emerged from a number of analyses we have conducted as part of the PDP program. In June, we presented findings from these analyses as part of several poster presentation made by ACADIA at the Movement Disorder Society's 14th International Congress On Parkinson's Disease and Movement Disorders. Our analyses are based on baseline data from our two initial Phase III PDP trials as well as data from our earlier Phase II PDP Proof of Concept study. These data compromise the largest data set, using SAPS in PDP, and involved nearly 500 PDP patients. Our analyses demonstrated a focus group of nine items from the hallucinations and delusions domain. Those SAPS best represents a clinical expression of psychosis in PD patients. You may recall as part of our preparations for the -020 Study during the second quarter we obtained feedback from the FDA in our new study design, which included the proposed refinement of the SAP Scale for use as a primary end point.

We were pleased that the FDA was supportive of our proposed study design. They accepted our proposed refinements of the SAP Scale for use as the primary end points in the -020 Study and agreed that this group of nine items would appear to have improved clinical relevance and face validity in PDP. By refining the end point to focus on the specific clinical features of PDP, we expect to reduce variability in the enhanced sensitivity of the measure for demonstrating treatment response. Let me now take a moment to provide you with further details on the design and objectives of the -020 Study. The study is expected to enroll about 200 patients, at approximately 50 clinical sites located in the United States. Patients will be randomized to two studies arms and receive oral doses of either 40-milligrams of pimavanserin or placebo once daily for six weeks. Patients will also continue to receive stable doses of their existing dopamine replacement therapy used to manage the motoric symptoms of Parkinson's Disease. In order to ensure that patients have adequate severity of Disease, we have increased the minimum required screening score from four to six on the Neuro Psychiatric Inventory, the NPI scale and will employ strictured psycho social interactions to support patients through the screening period. The trial is powered at a standard level for a pivotal study of 90%, to provide significant antipsychotic efficacy as a measure to using the SAPS. Motoric tolerability remains the key secondary end point in the trial and will be measured using Part 2 and 3 of the Unified Parkinson's Disease Rating Scale the UPDRS.

Our previous two studies were the largest PDP studies to date. We have been able to learn from this extensive data set. These learnings have guided the design enhancements incorporated in the -020 Study. We are confident that the new study designed will provide an increased opportunity to demonstrate efficacy with pimavanserin. In addition to the -020 Study, we are continuing to conduct an open-label safety extension study, which we refer to as the -015 Study. The -015 Study currently involves about 150 patients who completed our initial Phase III PDP trials. Patients who complete the -020 Study will also have the opportunity to enroll in the -015 Study, if in the opinion of the treating physician, the patient may benefit from continued treatment with pimavanserin. We recently presented an interim analysis of the -015 Study at the MDS Movement Disorder Society's 14th International Congress On Parkinson's Disease in June. This analysis suggests that the long-term administration of pimavanserin has been safe and well tolerated in this fragile elderly patient population with an underlying chronic neuro degenerative disease. Currently, mean treatment duration of the -015 Studies is about 11 months with total patient exposure equivalent to over 260 patient years. This study, coupled with a similar extension study in connection with our earlier Phase II PDP trial has generated a large amount of long-term safety data on pimavanserin.

Overall, in our Phase III and Phase II extension studies, a total of 168 patients have now been treated for over a year. 26 patients have been treated for over two years, and our longest single patient exposure is greater than five years. We continue to be encouraged to see that many patients have remained on pimavanserin for long periods of time. We believe that the favorable safety profile observed to date supports the potential of pimavanserin to offer significant advantages relative to current antipsychotics used off-label for the treatment of psychosis and Parkinson's Disease, as well as in Alzheimer's Disease. Let me now during the call back over to Uli.

Thank you, Roger. Let me now take a moment to highlight some market research on PDP, that we also presented at the recent Movement Disorder Society's International Congress On Parkinson's Disease. Our market research study indicates that physicians currently place multiple challenges with PDP. As a result, this disorder is under treated and represents a large, unmet medical need. PDP, affects up to 40% of Parkinson's patients, and deeply affects their quality of life. PDP, is associated with increased mortality, caregiver burden and is the major driver of the institutionalization among Parkinson's patients. We've no FDA approved therapy for PDP currently available, physicians may resort to using atypical antipsychotics off-label in an attempt to treat PDP. Our research indicates physicians are concerned with the use of existing antipsychotics, due to the safety and this may lead to the use of sub therapeutic doses. Among physician's key concerns was the potential for loss of motor symptom control in PDP patients. There remains a pressing need among patients, caregivers and physicians for a new treatment that is safe, effective, and well tolerated. We believe pimavanserin has the opportunity to be a First In Class therapy that will effectively treat PDP, without impairing motor function.

Let me now turn to the two other indications that we are pursuing with pimavanserin in our collaboration with Biovail. I'll begin with Alzheimer's Disease Psychosis or ADP. ADP is estimated to afflict 25% to 50% of the 5.3 million Alzheimer's Disease patients in the US. There is no proven safe and effective therapy for ADP. As is the case with PDP, as psychotic symptoms in ADP progress, physicians may resort to off-label use of antipsychotic medications. However current antipsychotics may exacerbate the cognitive disturbances associated with Alzheimer's Disease and are associated with numerous side effects. In fact, current antipsychotic medications have a Black Box Warning for use in elderly patients with dementia related psychosis due to increased mortality and morbidity. Pimavanserin selectively blocks the 5-HT2A receptor and in contrast to current antipsychotics, pimavanserin does not antagonize dopamine, histamine, or adrenaline receptors. Because of its selected 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 new treatment for ADP, that is safe, effective and well tolerated. We are continuing our preparations for a Phase II feasibility study, which we expect to start late this quarter to evaluate the potential of pimavanserin as a treatment for ADP. We expect this ADP study, which we refer to as the -019 Study, to involve about 160 patients. ACADIA will manage the -019 Study, after which, Biovail would be responsible for any further studies pursued by the parties for this indication.

Let's now turn to the Schizophrenia indication. Biovail announce in May, that it is planning for Phase III trials with pimavanserin together with risperidone as a combination therapy for patients with Schizophrenia. Biovail indicated that two pivotal studies would be required and that based on the need to complete routine safety assessments prior to initiating a Phase III trial, the first study may not commence until early in 2011. The Phase III program is expected to build on the positive results from ACADIA's Phase II co-therapy trial that we reported in 2007. Biovail would be accountable for the founding and execution of studies in this program, under the terms of our collaboration. Both Biovail and ACADIA believe that the opportunity for pimavanserin as a combination therapy with risperidone is an attractive option. Overall we are excited for the broad development strategy we are pursuing, which provides the opportunity to explore the clinical potential of pimavanserin over three different indications and to maximize the commercial value of this broader candidate in North America. While this collaborative effort clearly represents the core of our pimavanserin program, I want to remind you that we have retained all rights to pimavanserin in the rest of the world, which provides ACADIA with the opportunity to drive additional value for our stock holders.

Finally, I also want to mention that we have continued to establish a strong pattern portfolio around pimavanserin. This includes multiple issued patents that generically cover pimavanserin, as well as issued patents that specifically cover pimavanserin in the US, Europe and several additional cultures. The generic patents broadly claim chemical space that includes the structural pimavanserin, but the specific patents relate directly to its compositional matter. The European patent that specifically covers pimavanserin has been validated in 25 countries, including the largest European markets. The issued US patent that specifically claims pimavanserin expires in June 2027. We also have been awarded a US patent covering the crystal form of pimavanserin that is used for the pimavanserin tablets. This patent is not set to expire until June 2028. While pimavanserin is our most advanced product candidate, ACADIA also has other important programs in its pipeline. Through our long standing alliance with Allergan, we have two clinical stage product candidates that provide the potential for new treatment options in the areas of chronic pain, and glaucoma. First in the alpha agonist chronic pain program, Allergan has conducted several Phase II trials in this program and has announced that they are seeking a partner for the further development of this program and for commercialization in areas predominantly served by general practitioners. Second, in our muscarinic glaucoma program, Allergan is conducting Phase I development with our product candidate.

Through our collaboration with Meiji Seika, we are in IND-track development with AM-831. This compound which ACADIA discovered offers a new approach to treating Schizophrenia that may address cognition an untreated third dimension of this disease. In closing, we believe that our focus, on a portfolio of four product candidates, coupled with the broad development approach that we are pursuing with pimavanserin firmly positions ACADIA with multiple product and commercial opportunities and significant growth potential. We will now be happy to answer questions that you may have.

(Operator instructions) Your first question comes from the line of Charles Duncan with JMP Securities. Please proceed.

Hi, guys. Thanks for taking the question, and congratulations on getting the -020 Study started.

Thank you.

Uli, I wanted to ask you or Roger, if you would give us a little more color? It seemed like you outlined four big, kind of improvements to the previous trials that you believe will enhance the sensitivity and reduce the noise of that trial. And if you could just tell us what you think is the most important and then help us understand a little bit more about why fewer rating and assessments might be useful. And I've got some -- an additional follow-up to that.

So maybe Roger, you can start to try to give an answer here?

Yes, sure. Hi, Charles. I think the -- we obviously had a very large database to work from. We carefully went through the database and analyses to identify factors that were predictive or may have influenced the placebo response. In terms of the number of doses, there is a greater expectancy bias for two active doses versus placebo than there is on a 50/50 chance with two arms on that type of non-placebo. There was, as you can see, we have geographically focused a study on the United States, where we had the least variability in the data. And in the United States, we were able to employ centralized raters, where we used around about 10 raters across all the sites and the ratings are done by our video interview, which wasn't available in the rest of the world. The amendment to the primary end point came, as indicated in the call, from looking at the baseline values of how patients scored on the SAP Scale, a scale which is a recommended scale from the Movement Disorder Society, but one which has been adopted from Schizophrenia, initially adapted into PDP.

I think our huge database gives us an opportunity to further adapt it to really refine it down, to reflect the specific symtomology you get in PDP, and how that expresses itself on the SAP Scale. In terms of the fewer ratings and assessments, one of the factors in this is that, there is a much greater interaction at clinical trial between the physician and patient than one has in the normal, every day practice. And the bedside manner certainly leads to an improvement in patients. They feel the attention of the investigators, so therefore, our intention -- is to reduce some of those interactions, in order to take away some of that being in a study effect, that one gets from the increased opportunity to interact between the staff and patient.

Okay, that makes sense to me. You say that when you went to the FDA, and talked to them about the nine points versus all 20 in SAPS, you got some positive feedback. Do you know if they are looking at changing SAPS for other studies? And/or, did you ever consider getting a special protocol assessment? Or did you feel like you got all the feedback you could have gotten from the Agency?

I think we got very good feedback from the Agency. We based our approach to the Agency on the fairly extensive analyses of these patients and as we said before, it was about almost 500 patients that those analyses are based on so the largest database ever to examine this. The use of SAPS in other areas wouldn't be affected by the -- it was really specifically around the data generated in PDP patients. And therefore, clearly, was something which was evidence based in that discussion with FDA, but wouldn't necessarily be appropriate for the use of SAPS in the psychosis such as Schizophrenia.

Okay and then I think Tom actually kind of alluded to the timing of this being a two year study. What is the biggest factor that governs the time to enrollment in these patients? It seems like you've got a lot of experience studying these patients you probably know all the good centers, good enrolling centers. I'm just kind of wondering why it's going to take two years.

Perhaps I can take that, Roger. So first of all, we haven't guided on the precise time frame of this study. What we have said is that our previous experience, and particularly with the large PDP study that we conducted, the study that we call the -012 Study, which included a total of 300 patients, took about two years. And we provide that as sort of a guide, until we can come closer and more defined numbers to everybody. So that's where we are currently.

So it may actually be less than two years? If you were planning on 200 patients in this study?

Well, all we have said is that the last one was larger and took about two years. What I can also say is that we think there are several factors in the clinical study that in fact may benefit us here. One of them is that about 50% of the sites that intend to include in the clinical study are returning sites, so that should, in fact, favor a recruitments.

Okay. That helps. Now, I'm sorry for taking all this time. But, my next question is regarding the cash balance. You talked about anticipated payments and Tom, you did a great job laying out the funding, different funding responsibilities and how the terms worked. But are you anticipating beyond just reimbursement of expenses, are you anticipating getting any milestone-based payments? Like upon the completion, or start of a clinical trial or something like that?

Sure. Charles, let me clarify. Certainly, with respect to the runway, which we have said we expect the existing resources and those anticipated payments to carry us through the end of 2011, that does not factor in, any potential milestone. That only factors in the reimbursements that are for the contract and the various studies.

Okay. And with regard to Allergan, should they be successful in out licensing the neuropathic pain drug, would you get some of that payment?

Our terms on our Allergan arrangement are fixed, in terms of our opportunity. We are eligible for milestones and royalties, but not eligible for specific sub licensing fee.

Okay. And then my last question is with regard to Biovail, it sounds like they are still fully engaged in this program and perhaps even more so. How do you think they decided, or what was the basis of them, or you, choosing a 50% reimbursement for PDP, versus 100% reimbursement for ADP reimbursement?

Tom, if you want to take that?

Yes, Charles, Let me just -- I just want to correct one thing. In fact, they are fully funding the -020 Study. So it is 100% funding on their part. What was provided that if in fact it did not meet the primary end point, we would be responsible to reimburse 50% of that study.

I got you.

They fully fund the 100%. And then with respect to the ADP, that is the one where we fund the initial Phase II feasibility. But in fact, if that meets its end points and it is successful, then they would fully reimburse us for that study. These were items that had been negotiated in the collaboration.

Okay that makes more sense to me. Thanks for the clarification. I'll hop back in the queue.

Thanks.

Your next question comes from the line of Alan Carr with Needham & Company. Please proceed.

Hi, good afternoon, thanks for taking my questions.

Hi Alan.

Regarding the -020 Study, you mentioned that you had selected nine items in the SAPS instead of the 20 from the previous study. I'm wondering if you could tell us a bit more about the selection of those and to what extent that was based on experience from your previous Phase III trials versus what was known about this disease beforehand?

Roger, this is clearly your question.

Thanks, Uli. Hi, Alan. As I mentioned before, we took almost 500 patients. We actually took the baseline scores, so we weren't looking at necessarily the treatment effect but were actually looking at how patients presenting with the disease actually scored when you looked at the SAPS scale and then the questions. The hallucination delusion domain actually has 20 items included in it. A number of those are far more focused on Schizophrenia than the psychosis, which is seen in PDP. And much of it fits in with the previous description of PDP. But there is no data to really support that. What we now have is extensive data that we are able to perform the analyses on, in terms of looking at those particular items, that really reflected a moderate to severe issue for the patient. Also were frequent enough across the patient population. I should also add that not only were these items consistent across -- these nine items consistently scored across the population, but there was also validity across the various regions of the world. Really, so it's got not only validity in terms of the scoring but also cross cultural and geographical validity as well.

Okay. So, looking for a signal, essentially in the baseline numbers.

It was just looking not a signal of how it scores, and obviously, we did various analyses around there and we presented those as mentioned earlier. In the Movement Disorders Society meeting in June. We had a poster a couple of years ago looking at the Phase II study presented in Chicago. We updated it based on the Phase III studies that we had and all that baseline data this year in June.

Okay, then another question around the Alzheimer's trial that you are getting ready for, I mean, you've given us the, some little bit of information around the scale of it. I'm wondering what you can tell us about end points and the length of the trial, the measurement time period of the trial?

Maybe I can take that. We will clearly come back with much more detail when we start that study. What we can say now, is that we will, look at, it's a feasibility study, so we clearly want the study to tell us what is the best end point for Phase III studies. We expect to enroll about 160 patients. Looking at it will be a double blind placebo-controlled study. And probably compared placebo, probably the 40-milligram dose. We will probably study patients for 12 weeks.

I imagine you would probably be looking at some of the same SAPS issues, SAPS domains as in PDP? I'm not trying to tie anything down, but I imagine it'd be along those same lines.

We would look at several different efficacy measures. But that would be -- for example, the MPI, and several additional scales that are used to evaluate changes in psychosis and agitation and aggression. It would also include the clinical - impression as one of the more important data points. So again, the purpose of the study will be to understand and evaluate what is the best scale here to use for really understanding the effect of the drug on the psychosis and these patients.

Okay. And then one last question. Can you tell us about the [bd] environment and how the search is going to a partner for -105 and -106?

Yes. We clearly are interested in partnering, in particular of -105. Which for those of you don't remember, is a androgen receptor partial agonist, we have not said anything more in that backyard, interested in getting a partner for this program and that we are not currently moving it forward ourselves.

Okay. Thanks very much. Thanks for taking my questions.

Thanks.

Your next question is a follow-up from the line of Charles Duncan with JMP Securities. Please proceed.

Okay, thanks for taking my follow-up. Roger, you are probably back on the hot seat. I wasn't sure I understood, when you were describing in your prepared remarks, the scale. The screening scale going from four to six, could you explain that a little bit better? Or again?

Yes. I think that's comes back to, in terms of looking at the data, and looking at the likelihood of responding on the placebo, we felt that it was important to increase the baseline severity of patients, and thereby, hopefully, reduce the tendency to respond to the placebo.

Okay so you are basically a little bit more severe patients and therefore it's --

Yes.

-- it is maybe going to be a harder for them or their caregivers to do some of the other things that you mentioned like the bias or the expectations with regard to there being two doses versus one or something like that?

Yes. Obviously, we based this on the experience we have on the data from our previous studies.

Sure. Now, if you were to look at the different ways, I know you presented some of this data I've seen some of it, but I don't recall all of it. If you were to look at just the US patients, or if you were to use a refined scale like this, I understand it's a little bit of a post talk analysis, but what would your perspective be on the last set of trials in PDP, if you had used these? Like as an example, throw out the ex US patients.

I think what we, as you see from the design modifications we have made, we also based those on hypothesis around placebo response and then tested them with the data. What we are aiming for and would hope to see produced in the new study is a tightening of our data in line with those expectations.

Okay, then with regard to ADP, the ADP study, I'm sure you don't want to talk about when you think you can get that done, but it sounds like since it is a feasibility study, you have some flexibility on when you might take a look at how things are going in that study. Is it possible that, over the course of the next 12 or 18 months, you could have some sense as to how the ADP study is going?

Let me first answer you, Charles that we have no intention of conducting an interim analysis on that study. But what we have said is that we believe that both Schizophrenia Phase III study and the feasibility study in ADP, may be faster to conduct than the PDP study. We must again, in ADP, just like in PDP, we will come back and provide closer guidance in due time.

And is that simply a function of the incidents? Or is there a difference in the enrollment criteria? Or the way these patients are managed that make those studies PDP studies a little bit harder to enroll?

If you compare ADP and PDP, you have many more patients. That suffer from ADP. Because the Alzheimer's population is about 5.3 million in the US compared to 1.5 million Parkinson's patients. So there are more patients with ADP, than with PDP. Schizophrenia, same thing, more patients. So that is the reason for the different recruitment times, I think.

Okay. So it is really incidents based. It is not that you have extraordinarily difficult enrollment criteria in PDP?

Yes, I would say so.

Okay, good. Thanks for taking my follow ups.

Thank you.

There are no further questions. Dr. Hacksell, please proceed to closing remarks.

Okay. 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.