April 22, 2005

Acadia Pharma CEO Speech

Following are excerpts from a recent speech/presentation at a financial conference by the CEO of Acadia Pharmaceuticals, a small drug company working on new drugs to minimize the cognitive problems that are common in schizophrenia.

We are particularly interested in the developments at this company because of the nature of its work, and because it has been funded by the Stanley Medical Research Foundation - a private non-profit foundation focused on helping people who have schizophrenia and bipolar disorder.

This is an interesting collaboration between a non-profit group (acting as venture capitalist) and a for-profit company, and this may be a model that needs to be more common in a world where large pharma companies only go after "blockbuster" size drug targets. Ultimately, we need to see advocacy groups like NARSAD, NAMI or Schizophrenia Society in Canada, and SANE in the UK/Australia to start funding researchers that want to start small companies to speed the development of new drugs and therapies, and potentially even new stem cell treatments and gene therapy approaches (just to name a few) to treat schizophrenia and bipolar disorder.

There is a huge gap in the USA right now - between the basic research - and the funding for development of new drugs. Universities funded by the NIMH can only take a therapy so far - but large pharmaceutical companies will only pursue the drug if the market is $1 billion+, and they have many other distractions. This leaves many very promising treatments "stuck in the middle" between the NIMH basic research, and the huge market opportunities that large pharma will target.

Small biotech and drug companies targeting smaller new markets that range from $100 million to $500 million are having a very tough time getting funding for innovative new work like that being done by Acadia Pharma - and if we want to see the research move forward, we need to get non-traditional funding sources like NARSAD and NAMI to step up to the plate to start to fund these efforts. (of course, with the right venture-capital style advisory input).

The Juvenile Diabetes Research Foundation has been doing this with stem cell research already - why not other groups like NARSAD and NAMI? As we've seen with stem cell research in treatment of diabetes, the people with the most interest in seeing these new therapies being developed are frequently the families of the sufferers. If we don't act - frequently nobody else will, or if they do they'll do it much slower than we'd like. The progress in treatment of schizophrenia in the past 25 years has been abysmal - its time to change the model.


Let me give you a few facts about Acadia. We still relatively small company without 100 employees but we are international. We have chemistry operations in Scandinavia. We have biology, clinical developments and headquarters in San Diego and we went public last year.

I'll give you some more flavor on the commercial opportunities and let me start with the schizophrenia area. It is a huge market. It's served by anti-psychotics medications that apparently sell for more than $12 billion/year. You see some of the market leaders on the slide here. Number one in the market is Zyprexa sells more than $4.0 billion a year. These drugs are blockbusters despite the fact that they don't deal with the cognitive deficits associated with schizophrenia, which is one of the major reasons why patients cannot readjust to society. They're not detected in all patients. Additionally, about 30 percent of the patients are therapy resistant and in addition to that the drugs have nasty side effects.

Acadia's two programs in schizophrenia .. are targeted at some of the major problems in schizophrenia therapy.

The drug we are calling "ACP-103" is an adjunctive therapy in schizophrenia provides the opportunity to improve the therapeutic clinical profile of existing and psychotic drugs, and our other drug we call "ACP-104" - is a drug with an "atypical" anti-psychotic medication with cognitive benefits.

So let me start to take you to ACP-103 which is a very interesting small molecule [i.e. a drug taken in pill form]. It has ideal drug like properties. Great duration of action. Good pharma-kenetic properties. Excellent safety profile. Easy to synthesize and specificity for the right targets. The 5-HT to a-septor.

The concept behind developing ACP-103 absent adjunctive therapy in schizophrenia is related to the fact that its believed in order to have the optimal antipsychotic drug profile with cognitive benefits you want to completely block the [inaudible-highly accented] receptors in brain and partially - only partially block the D-2 receptors.

As you can see on this slide which represents ... values for some of the market leaders for example Zyprexa you don't have much of a separation between the potency to interact the D-2 receptors and one other 2A receptors. So with Zyprexa you either completely occupy both receptors which will lead to a lot of side effects or you only partially occupy both of them which will lead to less effectiveness.

By adding ACP-103 on the top Zyprexa you can see this ideal kind of pharmacological specificity having a complete occupants of the 2A receptors and a partial D-2 block. This will lead to reduced paring effect sometimes the data preview is less of the original and psychotic drug thereby we will have less target effects.

At the same time we will expand the efficacy so that the drug not only interacts with the targets that provide reduction of positive symptoms of schizophrenia but also start to move the efficacy into the negative symptom area which is very important in order to have ideal antipsychotic drug. And finally we also reduce the pharma D-2 induced side effects.

We believe that there is a huge potential for ACP-103 to improve the profile essentially in all antipsychotic drugs on the market - that's adjunctive therapy. We also see the potential commercially for ACP-103 to be developed as a combination pill for some of these leading antipsychotic areas that would provide drugs with better properties assisting antipsychotic and also provide opportunities for life extension.

The different doses that are represented on the slide represent doses that can be given to patients chronically or acutely -with the healthy volunteers without seeing any side effects whatsoever. So the slide seems to demonstrate that they have at least a 50 fold safety window for ACP-103 which is excellent.

This quarter we will also start a large study on adjunctive therapy of ACP-103 where we will begin ACP-103 on the top of low doses of Haloparidol or a low dose of Haloparidol and we will show in this trial that that kind of therapy will provide the same for better efficacy than high dose of Haloparidol and fewer side effects. So essentially this trial will highlight the advantages of adjunctive ACP-103 therapy.

The effective schizophrenia program with ACP-104 [which in many ways is very similar to Clozapine - but better, according to tests so far], which is a stand alone therapy for schizophrenia treatment, which will also provide cognitive benefits which is essentially unheard of in the antipsychotic world.

In a study that we reported last year, we could also demonstrate that patients that receive Clozapine, those patients receive great co-relation between ratios of plasma level of ACP 103 and Clozapine and clinical outcomes. So the higher the ratio is, the better the clinical outcome is in terms of outcome that represent cognitive benefits. So this is the clinical validation of the developing ACP104.

The ongoing Phase 2 program with ACP 104 consists of Scope 2 studies where primarily try to demonstrate the tolerability on pharma-genetics of ACP 104 but we also expect to see initial indications of application. Those studies will be reported in the second half of this year which will provide the basis for selecting the dose of ACP 104 that will be studied in a subsequent efficacy trial in which we test the ability of ACP 104 to reduce positive and negative symptoms of schizophrenia, as well as to improve cognitive abilities. This is a typical 42 day treatment schedule.

This program is supported a non-profit group (focused on helping people with schizophrenia and bipolar disorder) called the Stanley Medical Research Foundation with 6 million dollars. The reason why they decided to support this particular program is that it progresses cognitive aspects of schizophrenia in a very powerful way.

More information, see: Acadia Pharmaceuticals, Inc.


Particularly great news.

Posted by: CopperKettle at April 23, 2005 05:13 AM

Sounds promising. is ACP 104 FDA approved? is it available outside the USA?


Posted by: Josh at June 11, 2005 08:44 PM

This is a very inspiring article for us. My wife Usha is on Serenace 10mg and is not exactly helping her bouts of hallucination. She was on 5 mg and Doctor increased to 10 mg. I am looking for to read more on this and learn what best is available at Bangalore and her Doctor involved

Posted by: K Gurumurthy at December 24, 2006 06:46 AM

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