Proposed Alpha-7 (α7) Receptor Agonists

The lead investigational compound for the FORUM Pharmaceuticals alpha-7 (α7) program is encenicline hydrochloride (EVP-6124), a novel, orally administered, highly brain-penetrant, selective, and strong potentiator of the α7 receptor found on certain hippocampal and cortical neurons in the brain. Encenicline is believed to work in low concentrations as a co-agonist with naturally occurring acetylcholine to potentiate the response of α7 receptors—activated brain networks associated with sensory gating, attention, and cognition—thus priming these networks for improved neural processing and improved cognitive performance in areas such as memory and executive function.

COGNITIV Clinical Trial Program

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Encenicline is currently being evaluated in an ongoing Phase 3 COGNITIV clinical trial program to improve cognition in patients with Alzheimer’s disease (COGNITIV AD) and in patients with cognitive impairment associated with schizophrenia (COGNITIV CIAS).

Research Findings

Our Preclinical research has demonstrated that memory deficits can be minimized or reversed entirely by activating the α-7 receptor with encenicline alone or in combination with acetylcholinesterase inhibitors (AChE-Is) (for example, donepezil). Encenicline has also been shown to increase the release of important neurotransmitters, notably glutamate, which is believed to be important in the pathology of schizophrenia.

In July 2012, FORUM Pharmaceuticals announced positive results of its 6-month, double-blind Phase 2b clinical trial that evaluated encenicline against placebo in patients with mild to moderate Alzheimer’s disease. Results demonstrated that dosing with encenicline resulted in statistically significant improvements in cognition and clinical function, meeting both of the trial’s primary endpoints. The data also showed statistically significant results across secondary endpoints of other cognitive and clinical measures.

Additional pharmacokinetic and pharmacodynamic analyses from the Phase 2b trial released in October 2012 demonstrated a significant relationship (P=0.003) between encenicline plasma concentrations and the probability of experiencing an improvement in cognition.

In May 2011, the company announced positive top-line data from its double-blind, placebo-controlled Phase 2b clinical trial of encenicline in schizophrenia and presented a comprehensive analysis of these findings in December 2011. Results demonstrated encenicline’s statistically significant and clinically meaningful effects on both cognition and functional symptoms, including global cognitive function.