March 19, 2007

Acadia Pharma Talks about its New Schizophrenia Medications in Development

The following information may be of interest to families because it describes some new medications that are being developed for the treatment of schizophrenia. These new medications provide a hope that better treatments will eventually be available for people who have schizophrenia.

Acadia Pharmaceuticals, Inc. recently held their quarterly earnings conference call for investors, and discussed their efforts in development of new drugs that are targeted at treating schizophrenia. Following are some short excerpts from the transcript of this call. Keep in mind that this presentation is, in effect, a means to market the company to investors - and is a biased source of information (so some skepticism is appropriate). The executive team of any company is paid a lot of money to be excited about its products.

Because of this bias, some things that are not mentioned is risk that these products will not make it to market (i.e. be available for consumer purchase) because of problems that may be encountered during testing. Typically approximately 1 in 10 medications that make it to phase 2 testing, ultimately make it to consumer sales. Additionally, it will take many years to determine the side effects of the medications if they do make it to consumer sales. In general, medications definitely do help in the treatment of schizophrenia, but they frequently have side effects that cause significant problems for many users. Following is the excerpt:


ACADIA's pipeline includes five clinical programs. In our most advanced program, we are entering Phase III development with ACP-103 for the treatment of Parkinson's Disease Psychosis. We also have three Phase II stage clinical programs, including ACP-103 therapy as a co-therapy for schizophrenia, ACP-103 for the treatment of sleep maintenance insomnia, and ACP-104 as a stand-alone treatment for schizophrenia. We have retained worldwide commercialization rights for all four of these proprietary programs. In addition we have a neuropathic pain program in Phase II clinical trials in collaboration with Allergan.

Let me start by discussing our program, where we are developing ACP-103 as a co-therapy to be used together with other antipsychotic drugs to treat schizophrenia. We believe that co-therapy with ACP-103 may provide an important new treatment pattern for patients with schizophrenia. Current drugs used to treat this debilitating mental illness have substantial limitations, including severe side effects and lack of affect on the negative symptoms of schizophrenia. We believe that cotherapy with ACP-103 may result in enhanced efficacy, together with fewer side effects relative to existing treatments, thereby providing the potential to significantly improve therapy for patients suffering from schizophrenia.

We continue to be very pleased with the progress in the Phase II co-therapy trial that we are conducting in this program. As previously announced, we completed enrollment of this trial during the fourth quarter last year, ahead of schedule. We have also completed the treatment and related patient follow-up dates of the study, and we remain on track to report topline results from this study this month. Let me take a moment to review the design and key objectives of this trial. This Phase II trial is a double blind placebo-controlled six-week study, exploring the ability of ACP-103 when used together with low doses of each Risperidone, a commonly prescribed atypical antipsychotic drug, and Haloperidol, a typical antipsychotic drug, to provide an improved therapy for patients with schizophrenia.

We enrolled a total of 423 patients in the trial who were randomized to five different study arms. One, ACP-103 plus a low dose of Risperidone; two, ACP-103 plus a low dose of Haloperidol; three, a low dose of Risperidone plus placebo; four, a low dose of Haloperidol plus placebo; and five, a high-dose Risperidone plus placebo which was used as a control arm. Patients underwent a 42-day treatment schedule. The primarily end point of the study is antipsychotic efficacy that's measured after day 42 of treatment versus baseline in each of the ACP-103 treated arms, using the positive and negative syndrome scale, otherwise known as PANSS. This study is powered to show significant, up to 15% reduction in the PANSS score.

PANSS is an industry standard rating scale that is commonly used in schizophrenia trials. The scale includes 30 items which measured the severity of positive and negative symptoms and general psychopathology in patients with schizophrenia. Each item is rated on a scale of one to seven, with a score of one equivalent to absent and a score of seven equivalent to extreme.

In addition to evaluating the primary end point of the study, we will also be conducting secondary analyses which will include comparisons between the study arms. Our objectives of this trial are straight forward. First, we would like to demonstrate that ACP-103, when used in combination with low doses of either Risperidone or Haloperidol demonstrates antipsychotic efficacy and provides enhanced efficacy when compared to the low doses of Risperidone and Haloperidol alone. Second, we would like to demonstrate that the treatment arm with ACP-103 plus low dose Risperidone show a favorable side effect profile relative to the high dose Risperidone control arm. Third, we hope to see an expansion of antipsychotic efficacy into the negative symptom domain with the ACP-103 treatment groups.

We believe that this Phase II trial design provides the opportunity to demonstrate the key advantages of cotherapy with ACP-103. The limitations of currently available antipsychotics result in extremely poor patient compliance. This was clearly demonstrated in the KT study which was reported last year and which showed that 74% of patients taking atypical or typical antipsychotics discontinued their treatment within 18 months because of intolerable side effects or lack of efficacy. We believe that co-therapy with ACP-103 may address these large, unmet medical needs, and that it has the potential to significantly improve the standard of care for patients with schizophrenia.
We believe that ACP-103 will clearly differentiate itself from offlabel use of antipsychotics, as it is designed to effectively treat psychosis in patients with Parkinson's Disease without impairing motor function.

Let me now turn to our third proprietary clinical program, which is ACP-104, as a stand-alone treatment for schizophrenia. We believe that ACP-104 has the potential to be a major step forward in the treatment of schizophrenia. Current treatments are generally not effective in addressing negative symptoms and also are not -- or may in fact exacerbate cognitive disturbances associated with schizophrenia. ACP-104's unique pharmacological profile, combining M1 muscarinic agonism, 5-HT2A inverse agonist, and D2 and D3 partial agonists i may provide an atypical antipsychotic efficacy profile with the added advantage of improving cognitive function in patients with schizophrenia.

We have made considerable progress in this program. Last year we reported topline results from three initial clinical studies, which demonstrated that initial signals of antipsychotic affects as indicated by clinical meaningful reductions in PANSS scores were observed within the tolerated dose range of ACP-104. These initial studies provided us with a strong foundation to prepare for more advanced Phase II clinical trials.

We have made significant progress in our preparations for a multicenter double blind placebo-controlled six-week Phase II-b study with ACP-104 in patients with schizophrenia. Patients in this trial will be randomized to three different study arms, which will include two different doses of ACP-104 and one placebo arm. The primary end point will be psychotic efficacy as measured using the PANSS. We remain on track to initiate this Phase II-b study in the first half of 2007.

JOE PANTGINIS, ANALYST, CANACCORD ADAMS: Hi, guys. Thanks for taking the question. Two questions, please. The first one is with ACP-103. If you can just share with us again your partnering plans and/or progress around this program? And then I just follow-up with one other one.

ULI HACKSELL: Thank you, Joe. ACP-103 we have the following strategy. In schizophrenia, SMI, two indications where you need to have five large-sized organizations in order to be successful on the market. In these areas, we have the intentional completing the Phase II programs and when that is done, then we have analyzed the Phase II data, start to explore potential strategic alliances.

PATRICK MORIARTY, ANALYST, FORTIS: Hi. Thank you for taking my question. I have a question related to the low-dose Haldol arm in the ACP-103 schizophrenia trial. What receptors would you expect Haldol to be active at at these low doses?

ULI HACKSELL: Perhaps I can take this question. Haldol is, as you know, one of the oldest antipsychotic drugs. At higher doses, Haloperidol interacts with D2 receptors, D3 receptors and also alpha one receptors among other things. At this low dose, 2 milligrams a day, we don't expect that Haloperidol would have anything but an interaction with the D2 receptors. It's really a very interesting conceptual arm, if you wish, but we combined a pure D2 with a pure 5HT2A inverse agonist. So I think it's quite the interesting study in that sense.

PATRICK MORIARTY: So in that sense, you could almost consider this plus low dose -- I mean, this plus ACP-103 as more of a pure, atypical without the off-target affects. What do you think that would -- how would that play to EPS in general? Do you think you would need a 5-H21 or 5-HT3 affect in order to affect EPS, or is this the lead arm in the co-therapy trial?

ULI HACKSELL: Haloperidol is known to cause some extraparameter side effects. We also know from our previous efficacy studies with ACP-103 that we in fact can counteract psychotic-induced efficacy by giving ACP-103. We'll see how the data came out here. I think it's likely that ACP-103 versus the low dose Haloperidol will have a very nice profile for therapy. And it's likely to be similar to the low dose for ACP-103.

PATRICK MORIARTY: I had one follow-up question on ACP-106. There was some indications that really low-dose rise Risperidone, like the 1 mg dose has been effective in treatment-resistant depression. Is that something you would look at with ACP 106?

ULI HACKSELL: We haven't decided to look at any specific indications of the efficacy of that drug. Depression is certainly an area that would be interesting to explore with drugs of this type. Whether it would be specifically for treatment-induced depression or for other aspects of depression is something we haven't decided on yet.

EUN YANG, ANALYST, JEFFERIES & COMPANY: Thanks very much. A couple of questions on ACP-103 in schizophrenia agent therapy. I'm just wondering in terms of your plan for Phase III going forward, is that contingent upon -- does it depend on forming a partnership, or you are also thinking about moving forward on your own, depending on what you find in partnership discussions?

ULI HACKSELL: Thank you, Eun. Our strategy has been and still remains to when we have looked at the data in detail from the co-therapy trial to start out to evolve discounts and potential strategic alliances with strategic partners. The reason for this is that it's very difficult to really make a major impact in schizophrenia if you don't have behind you the major marketing organizations. They're competing with some of the largest organizations out there with the marketing organization, AstraZeneca, etc. If you want to really optimize the value of a drug like ACP-103 in schizophrenia, I think it's smartest and best to get a strategic alliance with someone that has that kind of potential to really compete successfully with these guys.

MARK MCIRNEY, ANALYST, VIVIAN ASSET MANAGEMENT: Hey, guys. How you doing? Just wanted to just kind of go quickly through your post Phase II partnership plans for 104. In addition, what your thoughts are about the cost and size of a Phase III study there considering some of the safety concerns?

ULI HACKSELL: Yes. So with ACP-104 in schizophrenia, we have essentially the same strategy with we have ACP-103 as a co-therapy schizophrenia. Then we have the Phase II-b data in hand, when we have completed the Phase II program with ACP-104, so established strong evidence of efficacy and also have initial safety data on the drug, we think that's the timing for exploring strategic alliances. Now if the second part of your question relates to safety concerns around ACP-104, specifically the related to the fact that [inaudible - heavy accent] and therefore we will need to demonstrate through clinical trials with ACP-104 that we don't cause acidosis.

We believe we will need to conduct the complete regulatory program with ACP-104 to demonstrate lack of agranulocytosis with this particular molecule. We also believe that already following the Phase II studies, we will have information if ACP-104 causes less leukopenia than you see. And that in itself will be a very interesting signal. It will not say anything definitive about the ability of ACP-104 to cause cirrhosis, but it will be an encouraging signal that we think is quite valuable.

MARK MCIRNEY: Right. But do you think you'll need to conduct a longer study than what would be customary for a Phase III antipsychotic, given the safety?

ULI HACKSELL: We think it's a relatively standard program for new psychotic drug will be required here.

More Information: Acadia Pharmaceuticals, Inc.


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