September 22, 2005 General News

ACADIA Pharmaceuticals Study Identifies Molecular Properties of ACP-104 That Predict Unique Antipsychotic Activity

ACP-104, Major Metabolite of Clozapine, Partially Activates Dopamine D2 and D3 Receptors

SAN DIEGO, Sept. 22 /PRNewswire-FirstCall/ — ACADIA Pharmaceuticals Inc. (Nasdaq: ACAD), a biopharmaceutical company utilizing innovative technology to fuel drug discovery and clinical development of novel treatments for central nervous system disorders, today announced publication of research in the Journal of Pharmacology and Experimental Therapeutics (JPET) that shows that ACP-104, the major metabolite of clozapine, is a partial agonist that causes weak activation of dopamine D2 and D3 receptors, whereas clozapine and most other antipsychotic drugs block these receptors. ACADIA believes that these partial agonist properties of ACP-104 may lead to less motoric side effects than seen with most other antipsychotic drugs. ACADIA is developing ACP-104 as a novel therapy for schizophrenia, with the added potential benefit of improving cognition.

“By combining D2 and D3 dopamine partial agonism, M1 muscarinic agonism, and 5-HT2A inverse agonism in a single molecule, ACP-104 uniquely addresses the three most promising target mechanisms for treating psychosis,” said Mark R. Brann, Ph.D., ACADIA’s President and Chief Scientific Officer. “We believe that ACP-104 represents a new and potential breakthrough approach in schizophrenia therapy.”

The JPET article (August 31, 2005, e-pub) describes the research conducted by ACADIA scientists of 41 marketed and experimental antipsychotic drugs and their ability to alter the activities of dopamine D2, D3, and D4 receptors. Using ACADIA’s proprietary R-SAT(R) technology platform, the scientists developed assays that detect subtle changes in the activities of these receptors. Among the 41 drugs, only two of them, ACP-104 and aripiprazole (marketed as ABILIFY(R)), were partial agonists causing weak activation of dopamine D2 and D3 receptors. Most antipsychotic drugs were shown to block these dopamine receptors. Prior research has shown that blockade of the dopamine receptors may cause undesirable motoric side effects, including Parkinson-like symptoms and tardive dyskinesia.

“Precisely balancing dopaminergic tone with an antipsychotic drug being a partial dopamine agonist is a very exciting concept that I have championed for many years,” said Arvid Carlsson, M.D., Ph.D., Professor Emeritus of Pharmacology at the University of Goteborg, Sweden, and winner of the 2000 Nobel Prize for Medicine. “I find it most intriguing that ACP-104, the major metabolite of the first atypical antipsychotic drug, clozapine, has this property.”

About ACP-104

ACP-104 is a small molecule drug candidate that ACADIA has discovered and is developing as a novel, stand-alone therapy for schizophrenia. It combines an atypical antipsychotic efficacy profile with the added potential benefit of improving cognition, one of the major challenges in treating schizophrenia today. ACP-104, or N-desmethylclozapine, is the major metabolite of clozapine, and has a unique ability to stimulate M1 muscarinic receptors. The M1 muscarinic receptors are widely known to play an important role in cognition. ACADIA is currently conducting initial Phase II studies to evaluate safety, tolerability, and preliminary efficacy of ACP-104 in 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 and social withdrawal. Cognitive disturbances often prevent patients with schizophrenia from readjusting to society and can require patients to be under medical care for their entire lives. Despite the availability of current antipsychotic drugs with worldwide sales of approximately $14 billion, cognitive disturbances are poorly addressed by existing therapies and represent a large unmet medical need in the treatment of schizophrenia.

About ACADIA Pharmaceuticals

ACADIA Pharmaceuticals is a biopharmaceutical company utilizing innovative technology to fuel drug discovery and clinical development of novel treatments for CNS disorders. ACADIA currently has four drug programs in clinical development as well as a portfolio of preclinical and discovery assets directed at large unmet medical needs, including schizophrenia, Parkinson’s disease, neuropathic pain, and glaucoma. Using its proprietary drug discovery platform, ACADIA has discovered all of the drug candidates in its product pipeline. ACADIA’s corporate headquarters is located in San Diego, California and it maintains research and development operations in both San Diego and Malmo, Sweden.

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 progress and timing of ACADIA’s drug discovery and development programs and related trials, the safety and efficacy of ACADIA’s drug candidates, and the benefits to be derived from ACADIA’s technology and drug candidates, in each case, including 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 discovery, development and commercialization. For a discussion of these and other factors, please refer to ACADIA’s annual report on Form 10-K for the year ended December 31, 2004 filed with the United States Securities and Exchange Commission as well as other subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are qualified in their entirety by this cautionary statement and ACADIA undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof.

ACADIA Pharmaceuticals Inc.
Lisa Barthelemy, Director, Investor Relations
(858) 558-2871

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