ACADIA Study Links ACP-104 (N-desmethylclozapine) to Improved Cognition in Schizophrenia Patients

ACADIA's Clinical Development of ACP-104 Supported by The Stanley Medical

Research Institute

Aug 03, 2004, 01:00 ET from ACADIA Pharmaceuticals Inc.

    SAN DIEGO, Aug. 3 /PRNewswire-FirstCall/ -- ACADIA Pharmaceuticals Inc.
 (Nasdaq:   ACAD), a biopharmaceutical company utilizing innovative science to
 fuel drug discovery and clinical development of novel treatments for central
 nervous system disorders, today announced publication of research linking the
 mechanism of ACP-104 (N-desmethylclozapine) to the ability of clozapine to
 improve cognition in patients with schizophrenia.  The research, conducted by
 scientists at ACADIA and Vanderbilt University and published in
 'Psychopharmacology' (July 16, 2004, e-pub), shows that ACP-104, the principal
 metabolite of clozapine, stimulates m1 muscarinic receptors in brain nerve
 cells that play an important role in cognition.
     ACADIA is developing ACP-104 as a novel therapy for schizophrenia with the
 added potential for improving cognitive function.  The clinical program for
 ACP-104 is supported in part through a three-year development agreement with
 The Stanley Medical Research Institute ("SMRI"), the leading nonprofit
 organization focused on cutting edge research into treatments for
     According to the published article, the muscarinic m1 receptor stimulating
 properties of ACP-104 are unique among all antipsychotic drugs and may be
 responsible for the superior clinical effects of clozapine.  The researchers
 observed that ACP-104, but not clozapine itself, is a potent and efficacious
 m1 muscarinic receptor agonist.  This finding resulted from a systematic
 profiling of a large number of neuropsychiatric drugs and their metabolites
 against a wide range of drug targets using ACADIA's proprietary functional
 assays.  ACADIA has built functional assays for the majority of the drug
 targets in the G-protein coupled receptor and nuclear receptor gene families.
     "It is widely appreciated that clozapine is unique among antipsychotic
 drugs in its ability to partially address the cognitive disturbances of
 schizophrenia," said Mark R. Brann, Ph.D., ACADIA's President and Chief
 Scientific Officer.  "The finding that ACP-104, clozapine's predominant
 metabolite, is a robust m1 muscarinic receptor agonist, while clozapine itself
 blocks this target, was an unexpected and truly exciting discovery.  By
 directly administering ACP-104, thereby avoiding the highly variable step of
 having it metabolized in the body from clozapine, we hope to offer an improved
 therapy that provides a more consistent cognitive benefit to patients," added
 Dr. Brann.
     The journal article also describes the analysis of drug blood levels
 relative to clinical response obtained in two clinical trials that included
 92 schizophrenia patients treated with clozapine.  This analysis showed that
 high ratios of ACP-104 relative to clozapine resulted in better response by
 these patients in a wide range of clinical measures reflecting cognitive
     "We are very excited by the finding that patients who form high levels of
 ACP-104 from clozapine show a cognitive improvement," said Dr. Michael Knable,
 Executive Director of SMRI.  "Treatment of cognitive deficits is perhaps the
 biggest challenge in schizophrenia therapy today.  ACP-104 with its unique
 muscarinic mechanism of action may provide a promising new approach to address
 cognition and improve the lives of patients with schizophrenia."
     About Schizophrenia
     Schizophrenia is a debilitating mental illness characterized by
 disturbances such as hallucinations and delusions as well as a range of
 negative symptoms, including cognitive disturbances.  Cognitive disturbances
 often prevent schizophrenia patients from readjusting to society and require
 patients to be under medical care for their entire lives.  Despite the
 availability of a variety of current antipsychotic drugs with worldwide sales
 exceeding $12 billion, cognitive disturbances are poorly addressed by existing
 therapies and represent a large unmet medical need in schizophrenia therapy.
     About ACADIA Pharmaceuticals
     ACADIA Pharmaceuticals is a biopharmaceutical company utilizing innovative
 science to fuel drug discovery and clinical development of novel treatments
 for central nervous system disorders.  ACADIA currently has five drug programs
 in clinical and preclinical development directed at large unmet medical needs
 and major commercial markets, including Parkinson's disease, schizophrenia,
 chronic pain, and glaucoma.  Using its proprietary drug discovery platform,
 ACADIA has discovered all of the drug candidates in its product pipeline.
 ACADIA's headquarters and biological research facilities are located in San
 Diego, California and its chemistry research facilities are located in
 Copenhagen, Denmark.
     About The Stanley Medical Research Institute
     The Stanley Medical Research Institute is the largest private source of
 research funding for severe mental illness and is based in Bethesda, Maryland.
 SMRI supports research in academic and corporate environments that is directly
 linked to discovering new treatments for schizophrenia and bipolar disorder.
 Further information about SMRI can be obtained at
     Forward Looking Statements
     Statements in this press release that are not strictly historical in
 nature are forward-looking statements.  These statements include but are not
 limited to statements related to the efficacy and development of ACP-104.
 These statements are only predictions based on current information and
 expectations and involve a number of risks and uncertainties.  Actual events
 or results may differ materially from those projected in any of such
 statements due to various factors, including the risks and uncertainties
 inherent in drug development and commercialization.  For a discussion of these
 and other factors, please refer to the company's registration statement on
 Form S-1 as well as other subsequent filings with the Securities and Exchange
     For further information, please contact:  Uli Hacksell, Ph.D., Chief
 Executive Officer of ACADIA Pharmaceuticals Inc., +1-858-558-2871.

SOURCE ACADIA Pharmaceuticals Inc.