FORUM Pharma Announces Publication Of Encenicline Phase II Clinical Trial Results For Cognitive Impairment In Schizophrenia

– Positive Effects of Encenicline on Cognitive Impairment and Real World Functioning Published in the Journal Neuropsychopharmacology –

WALTHAM, Mass.--(BUSINESS WIRE)--FORUM Pharmaceuticals Inc., a biopharmaceutical company singularly focused on the development and delivery of transformative medicines to treat serious brain diseases, today announced the peer-reviewed publication of results from its Phase 2 clinical trial of encenicline in schizophrenia patients with cognitive impairment. The trial evaluated the safety and efficacy of two doses of encenicline versus placebo in patients with schizophrenia treated with atypical antipsychotics. Results demonstrated statistically significant and clinically meaningful effect on both cognitive impairment and real world functioning, including the primary end point of global cognitive function. Encenicline is a novel alpha 7 agonist in Phase 3 development by FORUM to treat cognitive impairment in schizophrenia and Alzheimer’s disease. The study, “Randomized, Double-Blind, Placebo-Controlled Study of Encenicline, an a7 Nicotinic Acetylcholine Receptor Agonist, as a Treatment for Cognitive Impairment in Schizophrenia,” was published in the current online edition of the journal Neuropsychopharmacology [DOI 10.1038/npp.2015.176].

“Additionally, the FDA has awarded encenicline Fast Track designation for cognitive impairment in schizophrenia, highlighting the unmet medical need for a therapeutic to treat this debilitating condition”

“These Phase 2 trial results reported in Neuropsychopharmacology are the first statistically significantly positive data in a large randomized trial for cognitive impairment in schizophrenia,” said Dana C. Hilt, M.D., Senior Vice President, Clinical Development and Chief Medical Officer of FORUM. “Encenicline had positive effects in a number of cognitive and functional endpoints, and is the first drug candidate to demonstrate improvement using the MATRICS Consensus Cognitive Battery (MCCB), developed by the MATRICS project in conjunction with the National Institute of Mental Health and the U.S. Food and Drug Administration (FDA). These results were helpful in informing the dosing protocols and trial design of our two ongoing pivotal Phase 3 trials for encenicline in the treatment of cognitive impairment in schizophrenia. The COGNITIV SZ trials recently completed enrollment of more than 1,500 patients, and we expect top-line trial results in the first half of 2016.

“Additionally, the FDA has awarded encenicline Fast Track designation for cognitive impairment in schizophrenia, highlighting the unmet medical need for a therapeutic to treat this debilitating condition,” continued Dr. Hilt. “While atypical antipsychotics treat the positive symptoms of the disease, a procognitive agent to treat cognitive impairment and negative symptoms in schizophrenia could potentially improve functional outcomes for these patients. Encenicline could represent the first such novel treatment: a first-in-class alpha 7 agonist and a first potential treatment for cognitive impairment in schizophrenia.”

About the Encenicline Phase 2 Clinical Trial in Schizophrenia

The Phase 2 clinical trial was designed to evaluate the potential procognitive and functional effects of encenicline in patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotics. The trial was a 12-week, double-blind, randomized, placebo-controlled, parallel-design, multinational study conducted in 317 patients. Randomized patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotics were administered once daily doses of 0.27 or 0.9 mg of encenicline, or placebo.

Results demonstrated statistically significant and clinically meaningful effects on both cognitive impairment and real world functioning, including the primary endpoint of global cognitive function, as measured by the CogState Overall Cognition Index computerized battery test, for all encenicline-treated patients versus placebo, with the most effective dose being 0.27 mg (p=0.034). The MCCB (performed only in U.S. sites due to language availability) also showed a strong trend for improvement (p=0.069) in the 0.9 mg treatment group. Significant effects in the secondary endpoint of clinical function were observed with encenicline treatment as measured by the Schizophrenia Cognition Rating Scale (SCoRS) Interviewer Rating. The 0.9 mg dose group showed a statistically significant improvement (p=0.011) over placebo after three months of dosing. Improvement was also seen in the secondary endpoint assessing negative symptoms of schizophrenia, as measured by the Negative Subscale of the Positive and Negative Syndrome Scale (PANSS). The 0.9 mg dose group showed a statistically significant decrease in negative symptoms (p=0.028) compared to the placebo group after three months of dosing, with the 0.27 mg group also demonstrating a positive trend. Encenicline was well tolerated, with low discontinuation rates over three months of dosing in the study.

The full publication, “Randomized, Double-Blind, Placebo-Controlled Study of Encenicline, an a7 Nicotinic Acetylcholine Receptor Agonist, as a Treatment for Cognitive Impairment in Schizophrenia,” may be accessed online at: http://www.nature.com/npp/journal/vaop/naam/abs/npp2015176a.html.

About Encenicline

Encenicline is a novel, orally administered, highly brain-penetrant, selective, and potent agonist of the alpha 7 receptor found on hippocampal and cortical neurons involved in cognition. Encenicline is believed to work in low concentrations to prime the alpha 7 receptor to increase its response to acetylcholine, a naturally occurring neurotransmitter. This effect is thought to activate brain networks associated with sensory gating, attention, and cognition—thus enhancing these networks for improved neural processing and improved cognitive performance in areas such as memory and executive function. Encenicline is in development by FORUM Pharmaceuticals as a long-term treatment to improve cognitive function with sustained effect in schizophrenia and Alzheimer’s disease. In preclinical studies, alpha 7 agonists increased neuronal synchronization and enhanced synaptic plasticity, measured by an increase in long term potentiation (LTP). These effects may be linked to enhanced cognition not only in Alzheimer’s disease and schizophrenia, but suggest potential in other diseases with cognitive impairment.

Encenicline is the first alpha 7 agonist drug candidate to reach pivotal Phase 3 development. Two Phase 3 registration multi-center clinical trials (COGNITIV SZ) investigating the use of encenicline for cognitive impairment in schizophrenia have recently completed enrollment (www.clinicaltrials.gov registration numbers NCT01714661 and NCT01716975). Encenicline for the treatment of cognitive impairment in schizophrenia has received Fast Track designation by the U.S. Food and Drug Administration (FDA). Additionally, FORUM is investigating the use of encenicline for Alzheimer’s disease through a Special Protocol Assessment with the FDA. Two Phase 3 registration multi-center trials (COGNITIV AD) investigating the use of encenicline for Alzheimer’s disease are ongoing (www.clinicaltrials.gov registration numbers NCT01969123 and NCT01969136). FORUM has a license agreement with Mitsubishi Tanabe Pharma Corporation (MTPC) for the development and commercialization of encenicline in Alzheimer’s disease in Japan and several other Asian countries.

About Schizophrenia

Schizophrenia is a psychiatric disorder that affects approximately 2.2 million Americans, or about one percent of the adult population worldwide, and is usually diagnosed between 15 and 35 years of age. Symptoms of schizophrenia typically include positive and negative symptoms and cognitive impairment. “Positive” symptoms include hallucinations, delusions and paranoia. “Negative” symptoms include loss of motivation and interest in everyday activities, blunting of emotion, decrease in speech and social withdrawal. Cognitive impairments such as difficulty in attention, memory loss and problems processing information and decision-making are recognized as core disabling symptoms of schizophrenia linked to the functional impairment in this condition. The overall annual cost of schizophrenia in the U.S. is estimated at more than $62 billion, according to a study published in the Journal of Clinical Psychiatry.

About FORUM Pharmaceuticals Inc.

FORUM Pharmaceuticals Inc. (“FORUM Pharmaceuticals” or “FORUM”) is dedicated to developing transformative medicines to restore the minds of people with serious brain disease, empowering them to preserve their identity, dignity and the essence of what makes us human. The Company’s robust and diverse pipeline is focused on discovering and developing new treatments for important neurodegenerative diseases that explore novel mechanisms of action to potentially alter the progression of brain disease and provide improvement in cognitive and overall function. FORUM’s lead compound, encenicline, is currently being evaluated in separate ongoing Phase 3 clinical trial programs: COGNITIV SZ, which looks to improve cognitive impairment in patients with schizophrenia, and COGNITIV AD, which aims to improve cognition in patients with Alzheimer’s disease. The Company is also developing genetically targeted therapies, including FRM-0334, for the potential treatment of the ultra-orphan, rare disease frontotemporal dementia. Privately owned, FORUM Pharmaceuticals is based in Waltham, Mass. For more information about FORUM, visit www.forumpharma.com.

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