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Intra-Cellular Therapies Announces Topline Safety Results From Phase I/II Clinical Trial for ITI-007 in Healthy Geriatric Subjects and Patients With Dementia

Data From Part 1 of the Trial Will be Presented at the American Neurological Association Annual Meeting (ANA)

ITI-007 is Safe and Well-Tolerated With a Dose-Related Pharmacokinetic Profile in Geriatric Subjects Consistent With Previous Studies

NEW YORK, Oct. 13, 2014 (GLOBE NEWSWIRE) -- Intra-Cellular Therapies, Inc. (Nasdaq:ITCI), a biopharmaceutical company focused on the development of therapeutics for central nervous system (CNS) disorders, today announced topline results from ITI-007-200, a Phase I/II clinical trial designed to evaluate the safety, tolerability and pharmacokinetics of low doses of its lead drug candidate, ITI-007 in healthy geriatric subjects (trial Part 1) and in patients with dementia, including Alzheimer's disease (trial Part 2). The data presented at ANA relate to Part 1 of the trial. Additional data, including Part 2 of the trial, will be presented at a future scientific conference.

The initial results demonstrated that ITI-007 is safe and well-tolerated in healthy geriatric subjects and met the primary objectives of the study. Further, the results indicate a dose-related pharmacokinetic profile in geriatric subjects consistent with previous studies in younger subjects. This study marks an important milestone in defining the low dose range of ITI-007 to be developed for the treatment of behavioral disturbances associated with dementia and related disorders.

In these healthy geriatric subjects, ITI-007 was safe and well-tolerated at doses up to and including 30 mg. Subjects did not exhibit extrapyramidal adverse events or clinically relevant changes in cardiovascular parameters. The tolerability and pharmacokinetic profile of ITI-007 in geriatric subjects indicate a wide safety window for ITI-007 in the elderly.

Previous positron emission tomography studies demonstrated that a 10 mg dose of ITI-007 represented an approximate 10% occupancy of D2 receptors in the striatum. Doses of ITI-007 ranging from 1 to 10 mg resulted in improved sleep in patients with primary insomnia (clinical trial ITI-007-004). Taken together, these data indicate that low doses of ITI-007 demonstrate proof-of-mechanism by engaging key brain targets, and pharmacodynamic effects consistent with the mechanisms of action, and are safe and well tolerated in relevant patient populations. Based on previously reported data and the data from the geriatric study announced today, the Company plans to further evaluate low doses of ITI-007 for the treatment of behavioral disturbances associated with dementia, including Alzheimer's disease.

"Dementia is associated with behavioral symptoms including agitation, aggression, and irritability. These symptoms often gradually increase in frequency and severity during the course of the disease becoming distressing to patients and caregivers and contributing to early institutionalization," said Dr. Sharon Mates, Chief Executive Officer and Chairman. "We believe the ITI-007-200 results are consistent with the existing favorable safety and tolerability profile of the drug and its pharmacokinetic profile. The results allow the future testing of a range of low doses of ITI-007 that offer the potential clinical benefits of optimal 5-HT2A antagonism and additional potential benefits offered by the gradual engagement of other receptors as the dose is increased. The outcome of ITI-007-200 represents an important step forward in the clinical development of ITI-007 for the treatment of behavioral disturbances associated with dementia and related disorders, an indication with no FDA-approved drugs."

About the Phase I/II Clinical Trial

The ITI-007-200 clinical trial was conducted in two parts. Part 1 was a randomized, double-blind, placebo-controlled multiple ascending dose evaluation of ITI-007 in healthy geriatric subjects. In each cohort in Part 1, approximately ten subjects were randomized to receive ITI-007 (N=8) or placebo (N=2) orally once daily in the morning for seven days; doses of ITI-007 up to and including 30 mg were evaluated in three cohorts in Part 1. In Part 2, eight patients with dementia were randomized to receive 9 mg ITI-007 (N=5) or placebo (N=3) orally once a day in the evening for seven days. Safety and tolerability, and pharmacokinetic data were determined as the primary and secondary outcome measures.

Safety Profile of Low Doses of ITI-007 in the ITI-007-200 Trial

  • In healthy geriatric subjects, ITI-007 was safe and well tolerated up to and including a dose of 30 mg, the highest dose tested, administered once a day in the morning for 7 days.
  • The most frequent treatment-emergent adverse event (TEAE) was mild somnolence.
  • There were no serious TEAEs related to ITI-007, and no clinically significant changes in ECGs, vital signs or clinical laboratory values.
  • No motor impairment was noted at any dose of ITI-007 as assessed by the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS) and Simpson Angus Rating Scale (SAS).

Pharmacokinetic Profile of Low Doses of ITI-007 in the ITI-007-200 Trial

  • Pharmacokinetic results indicate that QAM dosing of ITI-007 leads to a linear and dose-related increase in blood drug levels in geriatric subjects.

About ITI-007

ITI-007 is our lead product candidate, whose mechanisms of action, we believe, have the potential to yield a first-in-class antipsychotic therapy and, at lower doses, a first-in-class therapy for the behavioral disturbances associated with dementia. In our pre-clinical and clinical trials to date, ITI-007 combines potent serotonin 5-HT2A receptor antagonism, dopamine receptor phosphoprotein modulation (DPPM), glutamatergic modulation and serotonin reuptake inhibition into a single drug candidate. At dopamine D2 receptors, ITI-007 has been demonstrated to have dual properties and to act as both a post-synaptic antagonist and a pre-synaptic partial agonist. ITI-007 has also been demonstrated to stimulate phosphorylation of glutamatergic NMDA NR2B, or GluN2B, receptors in a mesolimbic specific manner.

At the lowest dose studied to date (1 mg), ITI-007 has been demonstrated to act primarily as a potent 5-HT2A serotonin receptor antagonist. As the dose is increased, additional benefits are derived from the engagement of additional drug targets, including modest dopamine receptor modulation and modest inhibition of serotonin transporters. We believe that combined interactions at these receptors may provide additional benefits above and beyond selective 5-HT2A antagonism for treating agitation, aggression and sleep disturbances in diseases that include dementia, Alzheimer's disease and autism spectrum disorders, while avoiding many of the side effects associated with more robust dopamine receptor antagonism. As the dose of ITI-007 is further increased, leading to moderate dopamine receptor modulation, inhibition of serotonin transporters, and indirect glutamate modulation, these actions complement the complete blockade of 5-HT2A serotonin receptors. In this dose range, we believe that ITI-007 may be useful in treating the symptoms associated with schizophrenia, bipolar disorder, major depressive disorder and other neuropsychiatric diseases.

About Behavioral Disturbances in Dementia, Including Alzheimer's Disease

It has been estimated that 44.4 million people worldwide were living with dementia in 2013 including over five million patients with Alzheimer's disease in the United States. This number is expected to nearly double to 75.6 million by 2030 and to 135.5 million by 2050. While the diagnostic criteria for Alzheimer's disease and other dementias mostly focus on the related cognitive deficits, it is often the behavioral and psychiatric symptoms that are most troublesome for caregivers and lead to poor quality of life for patients. Several behavioral symptoms are quite prevalent in patients with dementia, including patients with Alzheimer's disease. Rates of depression in Alzheimer's disease are estimated to be up to 87%, although most estimates are between 30% and 50%. Agitation and aggression are present in approximately 60% of patients. Sleep disturbances, particularly as an increased likelihood of day-night reversal, are present in up to approximately 60% of patients. In view of the potential multiple effects of ITI-007 on aggression, agitation, sleep disorders and depression, and its safety profile to date, we believe that ITI-007 may provide a novel therapy for treating the behavioral disturbances accompanying dementia, including Alzheimer's disease.

The FDA has not approved any drug to treat the behavioral symptoms of dementia, including Alzheimer's disease. As symptoms progress and become more severe, physicians often resort to off-label use of antipsychotic medications in these patients. Current antipsychotic drugs are associated with a number of side effects, which can be problematic for elderly patients with dementia. In addition, antipsychotic drugs may exacerbate the cognitive disturbances associated with dementia. There is a large unmet medical need for a safe and effective therapy to treat the behavioral symptoms in patients with dementia, including Alzheimer's disease.

About Intra-Cellular Therapies

Intra-Cellular Therapies (the "Company") is developing novel drugs for the treatment of neuropsychiatric and neurodegenerative disease and other disorders of the central nervous system ("CNS"). The Company is developing its lead drug candidate, ITI-007, for the treatment of schizophrenia, behavioral disturbances in dementia, bipolar disorder and other neuropsychiatric and neurological disorders. The Company is also utilizing its phosphodiesterase platform and other proprietary chemistry platforms to develop drugs for the treatment of cognitive deficits in schizophrenia and other CNS disorders. The Company is also developing inhibitors against additional targets for CNS indications such as Alzheimer's disease, Parkinson's disease and depression and non-CNS indications such as cardiovascular disease.

Forward-Looking Statements

This news release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the progress and timing of our drug discovery and development programs; our beliefs about the potential uses and benefits of ITI-007 for the treatment of behavioral disturbances associated with dementia, including Alzheimer's disease; our plans for the future testing of a range of low doses of ITI-007; and our research and development efforts and plans under the caption "About Intra-Cellular Therapies, Inc." All such forward-looking statements are based on management's present expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to the following: our current and planned clinical trials for ITI-007 and our other product candidates may not be successful or may take longer and be more costly than anticipated; product candidates that appeared promising in earlier research and clinical trials may not demonstrate safety and/or efficacy in larger-scale or later clinical trials; our reliance on collaborative partners and other third-parties for development and commercialization of our product candidates; and the other risk factors discussed under the heading "Risk Factors" contained in our Annual Report on Form 10-K for the year ended December 31, 2013 filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our periodic and current reports. All statements contained in this press release are made only as of the date of this press release, and we do not intend to update this information unless required by law.

CONTACT: Intra-Cellular Therapies, Inc. Juan Sanchez, M.D. Vice President, Corporate Communications and Investor Relations 212-923-3344 Burns McClellan, Inc. Lisa Burns/Angeli Kolhatkar (Investors) Justin Jackson (Media) jjackson@burnsmc.com 212-213-0006

Source:Intra-Cellular Therapies, Inc.