SAN DIEGO—(BUSINESS WIRE)—July 13, 2006—ACADIA PharmaceuticalsInc. (Nasdaq:ACAD), a biopharmaceutical company utilizing innovativetechnology to fuel drug discovery and clinical development of noveltreatments for central nervous system disorders, today announcedresults from three initial clinical studies of ACP-104 in patientswith schizophrenia. The results of these studies demonstrated thatACP-104 is safe and well tolerated after repeated dosing of up to 600mg per day, and that initial signals of antipsychotic effects wereobserved within the tolerated dose range of ACP-104. In addition,plasma levels of ACP-104 correlate with brain receptor occupanciesindicating good penetration of ACP-104 into the brain. The threestudies enrolled an aggregate of 74 patients with schizophrenia andwere conducted in collaboration with Professor Carol Tamminga, M.D.,from the University of Texas Southwestern Medical School in Dallas,Texas.
"The first three clinical trials of ACP-104 were successful inthat they demonstrated a solid safety and tolerability profile for thecompound and provided encouraging indications of antipsychoticactivity in patients with schizophrenia," said Dr. Tamminga, PrincipalInvestigator of the ACP-104 clinical studies. "Tolerability was betterthan anticipated and, in general, the patients in these studiespositively evaluated their experience with ACP-104. These studyresults show the potential of ACP-104 as an innovative therapy forpatients with schizophrenia and strongly support its furtherdevelopment."
Single Ascending-Dose Study
The first clinical trial was a randomized, double-blind,placebo-controlled, single ascending-dose study primarily designed toevaluate the safety, tolerability and pharmacokinetics of ACP-104 inpatients with schizophrenia. A total of 24 patients were enrolled inthe study and were assigned to one of five treatment cohorts. Withineach cohort, each patient received placebo and two distinct doses ofACP-104 ranging from 25 mg to 250 mg on separate days.
Results of this study show that ACP-104 is safe and well toleratedat all doses tested. No dose-limiting toxicities or serious adverseevents were observed in the study and a maximum tolerated dose was notreached. All adverse events were mild to moderate in severity, withthe most frequent being sedation. No significant changes were observedin safety parameters such as electrocardiogram (ECG) measures(including QT/QTc interval), clinical chemistries and hematology. Noextrapyramidal side effects were observed in the patients.
Multiple Ascending-Dose Study
The second clinical trial was a 14-day, steady-state,double-blind, placebo-controlled multiple ascending-dose study inpatients with schizophrenia. This study was primarily designed toevaluate the safety, tolerability and pharmacokinetics of ACP-104, aswell as to explore preliminary signals of antipsychotic effects. Atotal of 40 patients with schizophrenia were enrolled in the study insix dose cohorts. The patients were randomly assigned to ACP-104 orplacebo in a treatment-to-placebo ratio of about 3:1. The patientswere treated with escalating daily doses of ACP-104 ranging from 100mg (50 mg twice-daily) to 800 mg (400 mg twice-daily) for 14 days. Inthe first four cohorts, patients received a fixed dose of ACP-104 orplacebo for the first four days, and then the patients were escalatedto a higher dose for the remaining ten days of the study. In the lasttwo cohorts involving the 600 mg and 800 mg doses, there was atitration period followed by a period of fixed dosing.
The results of this study indicate that ACP-104 is safe and welltolerated at doses tested up to 600 mg per day, a dose considered tobe the maximum tolerated dose in the study. Although this was a smallstudy with a limited treatment duration, initial signals ofantipsychotic effects, as indicated by reductions in Positive andNegative Syndrome Scale (PANSS) scores, were observed in patientsgiven the two highest tolerated doses (400 mg and 600 mg) of ACP-104.
Adverse events were generally mild to moderate in severity. Themost common adverse events included sleepiness, increased salivation,constipation, and tachycardia (an increased heart rate). Nosignificant changes were observed in safety parameters such as ECGmeasures (including QT/QTc interval), and clinical chemistries. Noextrapyramidal side effects were observed in the patients.
Six patients were discontinued in the study for adverse events,including three patients from the 800 mg cohort. Two of the adverseevents were classified as serious adverse events, including oneinstance of a seizure deemed by the investigator as unrelated to thestudy drug, and one instance of a short-lasting fever of unknownorigin. The fever was subsequently followed three days later by atransient and mild decrease in white blood cell counts referred to asmild leukopenia that was deemed most likely due to viral infection,but a possible relationship to the study drug could not be ruled out.The other four adverse events leading to discontinuation includedinstances of tachycardia and hypertension, which were deemed relatedto the study drug, and one instance of a fever, which was deemedunrelated to the study drug.
Positron Emission Tomography Study
The third study was an open label single-dose positron emissiontomography (PET) study that was designed to determine the relationshipbetween plasma levels of ACP-104 and occupancy of 5-HT(2A) receptorsin the brain. A total of 10 patients with schizophrenia were enrolledin the study and received single oral doses of ACP-104 ranging from 25mg to 150 mg. There was a relationship between plasma levels ofACP-104 and the degree of 5-HT(2A) receptor occupancy at all dosesindicating good penetration of ACP-104 into the brain. Both the 100 mgand 150 mg doses of ACP-104 yielded significant 5-HT(2A) receptoroccupancy comparable to that previously seen with clozapine atclinically effective doses.
"The demonstration that high doses of ACP-104 are well toleratedand provide signals of antipsychotic effects, coupled with thecorrelating plasma levels and brain receptor occupancies establishes astrong foundation for pursuing more advanced clinical studies withACP-104, including a subsequent Phase IIb clinical trial," said UliHacksell, Ph.D., Chief Executive Officer of ACADIA.
About ACP-104
ACP-104, or N-desmethylclozapine, is the major metabolite ofclozapine, and is being developed by ACADIA as a novel, stand-alonetherapy for schizophrenia. It combines an atypical antipsychoticefficacy profile with the added potential benefit of enhancedcognition, thereby addressing one of the major challenges in treatingschizophrenia today. ACP-104 combines M(1) muscarinic agonism,5-HT(2A) inverse agonism, and D(2) and D(3) dopamine partial agonismin a single compound and, therefore, uniquely addresses what ACADIAbelieves are the three most promising target mechanisms for treatingschizophrenia. ACADIA's development program for ACP-104 is supportedin part by the Stanley Medical Research Institute (SMRI). SMRI is thelargest private source of research funding in the United States forsevere mental illness and is based in Bethesda, Maryland.
About Schizophrenia
Schizophrenia is a chronic disabling mental illness characterizedby disturbances such as hallucinations and delusions as well as arange of cognitive disturbances and negative symptoms, includingsocial withdrawal. Cognitive disturbances and negative symptoms arebelieved to be the major cause of patients' functional impairment andoften prevent patients with schizophrenia from being fullycontributing members of society. Despite the availability of currentantipsychotic drugs with worldwide sales of approximately $14 billionin 2004, cognitive disturbances are poorly addressed by existingtherapies and represent a large unmet medical need in the treatment ofschizophrenia.
About ACADIA Pharmaceuticals
ACADIA is a biopharmaceutical company utilizing innovativetechnology to fuel drug discovery and clinical development of noveltreatments for central nervous system disorders. ACADIA currently hasfive Phase II-stage clinical programs as well as a portfolio ofpreclinical and discovery assets directed at large unmet medicalneeds, including schizophrenia, Parkinson's disease, sleep maintenanceinsomnia, and neuropathic pain. All of the drug candidates in ACADIA'sproduct pipeline emanate from discoveries made using its proprietarydrug discovery platform. ACADIA's corporate headquarters is located inSan Diego, California and it maintains research and developmentoperations in both San Diego and Malmo, Sweden.
Forward-Looking Statements
Statements in this press release that are not strictly historicalin nature are forward-looking statements. These statements include butare not limited to statements related to the potential for ACP-104 asa therapy for schizophrenia, any potential cognitive or other benefitsof ACP-104, the safety, tolerability and efficacy of ACP-104, andfuture clinical trials of ACP-104. These statements are onlypredictions based on current information and expectations and involvea number of risks and uncertainties. Actual events or results maydiffer materially from those projected in any of such statements dueto various factors, including the risks and uncertainties inherent indrug discovery, development and commercialization, collaborations withothers and litigation. For a discussion of these and other factors,please refer to ACADIA's annual report on Form 10-K for the year endedDecember 31, 2005 filed with the United States Securities and ExchangeCommission as well as other subsequent filings with the Securities andExchange Commission. You are cautioned not to place undue reliance onthese forward-looking statements, which speak only as of the datehereof. This caution is made under the safe harbor provisions of thePrivate Securities Litigation Reform Act of 1995. All forward-lookingstatements are qualified in their entirety by this cautionarystatement and ACADIA undertakes no obligation to revise or update thispress release to reflect events or circumstances after the datehereof.
CONTACT: ACADIA Pharmaceuticals Inc.
Lisa Barthelemy, Director, Investor Relations
Uli Hacksell, Ph.D., Chief Executive Officer
(858) 558-2871
SOURCE: ACADIA Pharmaceuticals Inc.