Intra-Cellular Therapies Announces Enrollment of Clinical Trial

Intra-Cellular Therapies, Inc. recently announced the company has commenced enrollment in the ITI-214-105 Phase 1/2 clinical trial in patients with Parkinson’s disease (PD).

“ITI-214 is a potent and selective phosphodiesterase 1 (PDE1) inhibitor. Following the favorable safety and tolerability results in our Phase 1 program, we are pleased to announce the advancement of ITI-214 for the treatment of patients with Parkinson’s disease,” said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. “This study is designed to evaluate the safety and tolerability of ITI-214 in this patient population, as well as evaluate the ability of ITI-214 to treat both motor and non-motor symptoms associated with Parkinson’s disease and to provide a framework for future trials to assess disease modification.”

This is a Phase 1/2 randomized, double-blind, placebo-controlled, multiple rising dose study of ITI-214 in patients with idiopathic PD. Patients with mild to moderate PD who are maintained on stable PD therapy will be randomly assigned to placebo or ITI-214 1, 3 or 10 mg administered orally once daily for 7 days. The primary objective is to evaluate the safety and tolerability of ITI-214 in this patient population. Secondary objectives are to evaluate the pharmacokinetic profile of ITI-214 and explore its potential utility to control motor fluctuations and to evaluate treatment of non-motor symptoms (daytime sleepiness, dysautnomia) associated with PD. Biomarkers of disease progression (inflammation) will be assessed.

ITI-214 is a potent and selective phosphodiesterase 1 (PDE1) inhibitor. As the clinical lead compound in the Company’s PDE1 portfolio, ITI-214 has been found to be generally well tolerated with a favorable safety profile in four Phase 1 clinical trials in healthy volunteers as well as patients with schizophrenia. Inhibitors of PDE1 block the breakdown of cyclic nucleotides (cAMP, cGMP), potentiating downstream intracellular signaling. The PDE1 enzyme is highly active in pathological or disease states, and our PDE1 inhibitors are designed to reestablish normal function in these disease states. PDE1 inhibitors have minimal effect on normal function, only acting when cells in the nervous system are stimulated. These “on-demand” effects make this an exciting and novel approach for the treatment of disease. In animal models, inhibition of PDE1 has been shown to reduce neuroinflammation and to reduce neurodegeneration. The mechanism of action of PDE1 inhibitors suggests therapeutic potential across a variety of neurological and cardiovascular diseases.

Preclinical studies suggest that PDE1 inhibitors potentiate L-DOPA and other dopamine replacement therapies for motor symptom control at lower doses of dopamine replacement therapies while inhibiting the adverse dyskinesias induced by these treatments. Preclinical models have also shown the potential for PDE-1 inhibitors to address non-motor symptoms such as excessive daytime sleepiness, cognitive impairment and other non-motor symptoms. In preclinical studies, the Company has recently demonstrated the importance of ITI-214 and inhibition of PDE1 in reducing neuroinflammation and in regulating microglial function suggesting utility in treating neurodegenerative and neuropsychiatric disease.

Over 1 million and 1.2 million patients in the United States and Europe, respectively, live with Parkinson’s disease. PD is a progressive neurodegenerative disorder largely affecting dopamine systems in the brain and characterized by motor impairment and nonmotor symptoms, including but not limited to excessive daytime sleepiness, cognitive impairment, mood disorders and dysautonomia. Dopamine replacement therapies, with L-DOPA, address early motor symptoms, but are insufficient as the disease progresses and have limiting side effects. There remains a large unmet need for effective treatments to sustain the utility of dopaminergic therapies and to address nonmotor symptoms.

Intra-Cellular Therapies is developing novel drugs for the treatment of neuropsychiatric and neurodegenerative diseases and diseases of the elderly, including Parkinson’s and Alzheimer’s disease. The Company is developing its lead drug candidate, lumateperone (also known as ITI-007), for the treatment of schizophrenia, bipolar disorder, behavioral disturbances in patients with dementia, including Alzheimer’s disease, depression and other neuropsychiatric and neurological disorders. Lumateperone, a first-in-class molecule, is in Phase 3 clinical development for the treatment of schizophrenia, bipolar depression and agitation associated with dementia, including Alzheimer’s disease. The Company is also utilizing its phosphodiesterase (PDE) platform and other proprietary chemistry platforms to develop drugs for the treatment of CNS and other disorders. The lead molecule in the Company’s PDE1 portfolio, ITI-214 is in development for the treatment of symptoms associated with Parkinson’s disease. Ultimately, treatments are needed that protect dopamine containing neurons from damage, providing novel approaches for slowing or halting disease progression. The impact of ITI-214 may be examined in future, longer term studies. For more information, visit www.intracellulartherapies.com.