ACP-104, Major Metabolite of Clozapine, Partially Activates Dopamine D2 andD3 Receptors
SAN DIEGO, Sept. 22 /PRNewswire-FirstCall/ —ACADIA Pharmaceuticals Inc.(Nasdaq: ACAD), a biopharmaceutical company utilizing innovative technology tofuel drug discovery and clinical development of novel treatments for centralnervous system disorders, today announced publication of research in theJournal of Pharmacology and Experimental Therapeutics (JPET) that shows thatACP-104, the major metabolite of clozapine, is a partial agonist that causesweak activation of dopamine D2 and D3 receptors, whereas clozapine and mostother antipsychotic drugs block these receptors. ACADIA believes that thesepartial agonist properties of ACP-104 may lead to less motoric side effectsthan seen with most other antipsychotic drugs. ACADIA is developing ACP-104as a novel therapy for schizophrenia, with the added potential benefit ofimproving cognition.
"By combining D2 and D3 dopamine partial agonism, M1 muscarinic agonism,and 5-HT2A inverse agonism in a single molecule, ACP-104 uniquely addressesthe three most promising target mechanisms for treating psychosis," said MarkR. Brann, Ph.D., ACADIA's President and Chief Scientific Officer. "We believethat ACP-104 represents a new and potential breakthrough approach inschizophrenia therapy."
The JPET article (August 31, 2005, e-pub) describes the research conductedby ACADIA scientists of 41 marketed and experimental antipsychotic drugs andtheir ability to alter the activities of dopamine D2, D3, and D4 receptors.Using ACADIA's proprietary R-SAT(R) technology platform, the scientistsdeveloped assays that detect subtle changes in the activities of thesereceptors. Among the 41 drugs, only two of them, ACP-104 and aripiprazole(marketed as ABILIFY(R)), were partial agonists causing weak activation ofdopamine D2 and D3 receptors. Most antipsychotic drugs were shown to blockthese dopamine receptors. Prior research has shown that blockade of thedopamine receptors may cause undesirable motoric side effects, includingParkinson-like symptoms and tardive dyskinesia.
"Precisely balancing dopaminergic tone with an antipsychotic drug being apartial dopamine agonist is a very exciting concept that I have championed formany years," said Arvid Carlsson, M.D., Ph.D., Professor Emeritus ofPharmacology at the University of Goteborg, Sweden, and winner of the 2000Nobel Prize for Medicine. "I find it most intriguing that ACP-104, the majormetabolite of the first atypical antipsychotic drug, clozapine, has thisproperty."
About ACP-104
ACP-104 is a small molecule drug candidate that ACADIA has discovered andis developing as a novel, stand-alone therapy for schizophrenia. It combinesan atypical antipsychotic efficacy profile with the added potential benefit ofimproving cognition, one of the major challenges in treating schizophreniatoday. ACP-104, or N-desmethylclozapine, is the major metabolite ofclozapine, and has a unique ability to stimulate M1 muscarinic receptors. TheM1 muscarinic receptors are widely known to play an important role incognition. ACADIA is currently conducting initial Phase II studies toevaluate safety, tolerability, and preliminary efficacy of ACP-104 in patientswith schizophrenia.
About Schizophrenia
Schizophrenia is a debilitating mental illness characterized bydisturbances such as hallucinations and delusions as well as a range ofnegative symptoms, including cognitive disturbances and social withdrawal.Cognitive disturbances often prevent patients with schizophrenia fromreadjusting to society and can require patients to be under medical care fortheir entire lives. Despite the availability of current antipsychotic drugswith worldwide sales of approximately $14 billion, cognitive disturbances arepoorly addressed by existing therapies and represent a large unmet medicalneed in the treatment of schizophrenia.
About ACADIA Pharmaceuticals
ACADIA Pharmaceuticals is a biopharmaceutical company utilizing innovativetechnology to fuel drug discovery and clinical development of novel treatmentsfor CNS disorders. ACADIA currently has four drug programs in clinicaldevelopment as well as a portfolio of preclinical and discovery assetsdirected at large unmet medical needs, including schizophrenia, Parkinson'sdisease, neuropathic pain, and glaucoma. Using its proprietary drug discoveryplatform, ACADIA has discovered all of the drug candidates in its productpipeline. ACADIA's corporate headquarters is located in San Diego, Californiaand it maintains research and development operations in both San Diego andMalmo, Sweden.
Forward-Looking Statements
Statements in this press release that are not strictly historical innature are forward-looking statements. These statements include but are notlimited to statements related to the progress and timing of ACADIA's drugdiscovery and development programs and related trials, the safety and efficacyof ACADIA's drug candidates, and the benefits to be derived from ACADIA'stechnology and drug candidates, in each case, including ACP-104. Thesestatements are only predictions based on current information and expectationsand involve a number of risks and uncertainties. Actual events or results maydiffer materially from those projected in any of such statements due tovarious factors, including the risks and uncertainties inherent in drugdiscovery, development and commercialization. For a discussion of these andother factors, please refer to ACADIA's annual report on Form 10-K for theyear ended December 31, 2004 filed with the United States Securities andExchange Commission as well as other subsequent filings with the Securitiesand Exchange Commission. You are cautioned not to place undue reliance onthese forward-looking statements, which speak only as of the date hereof.This caution is made under the safe harbor provisions of the PrivateSecurities Litigation Reform Act of 1995. All forward-looking statements arequalified in their entirety by this cautionary statement and ACADIA undertakesno obligation to revise or update this press release to reflect events orcircumstances after the date hereof.
Contacts:
ACADIA Pharmaceuticals Inc.
Lisa Barthelemy, Director, Investor Relations
(858) 558-2871