Bionomics Limited (ASX:BNO, OTCQX:BNOEF), a biopharmaceutical company focused on the discovery and development of innovative therapeutics for the treatment of diseases of the central nervous system (CNS) and cancer, today reported positive data from the completed Phase 1 multiple ascending dose, placebo controlled clinical trial of BNC210, an orally administered negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor (alpha-7 receptor) being developed for the treatment of anxiety and depression. The results showed that BNC210 was safe and well-tolerated, and consistent with its mechanism of action at the α7 receptor, showed that BNC210 significantly reduced the effect of nicotine as measured by electrocephalogram (EEG).
Dr. Philippe Danjou, Senior Director, Research and Development at Biotrial, said, "BNC210 has shown an encouraging safety and tolerability profile and the demonstration that BNC210 modulates nicotine-dependent changes as measured by EEG provides evidence of target engagement. These data support the continued development of BNC210 in this area of great unmet medical need."
In the study, a total of 54 healthy volunteers were enrolled and dosed for eight consecutive days, with 42 subjects receiving BNC210 (300mg - 2,000mg total dose per day) and 12 placebo. In addition to detailed safety evaluations, all study subjects underwent a standard battery of assessments measuring cognitive parameters. Subjective feelings produced by BNC210 were also assessed. Study results showed BNC210 was safe and well tolerated at all dose levels, and a maximum tolerated dose was not reached. No subject discontinued due to treatment-emergent adverse events. BNC210 administration did not result in adverse changes in cognition. The Bond & Lader Visual Analog Scales showed that there were no adverse changes in subjects' ratings of subjective feelings around alertness, contentedness or calmness and the Addiction Research Centre Inventory 49 check-list (ARCI49) indicated that BNC210 administration did not result in feelings associated with drugs of abuse.
An additional pharmacodynamic test, the nicotine shift assay, was performed in subjects receiving either the highest dose of BNC210 or placebo. Subjects, all non-smokers, were administered nicotine by nasal spray with responses measured by EEG. Of the 30 subjects administered with nicotine prior to administration of either BNC210 or placebo, 13 responded to nicotine in a dose dependent manner. These nicotine responders were selected for analysis. When the study was unblinded, twelve of the nicotine responders received BNC210 whilst one nicotine responder received placebo. Eleven BNC210-treated subjects showed evidence of reduction in nicotine-induced EEG measures relative to relative to baseline whilst one BNC210- treated subject and the placebo-treated subject showed no changes in nicotine-induced EEG measures. Overall BNC210 treatment significantly reduced EEG changes induced by half milligram incremental doses of nicotine from 0.5 to 2 mg (p<0.02 - 0.0009).
Bionomics' CEO & Managing Director Dr. Deborah Rathjen said "BNC210 exemplifies Bionomics' mission of discovering and developing proprietary, first in class drug candidates with the potential to significantly benefit patients. We believe BNC210 may offer differentiation from currently-approved drugs for the treatment of anxiety and depression."
"We look forward to progressing our current Phase 2 trial in patients with Generalized Anxiety Disorder and to considering other potential indications for BNC210 within the spectrum of anxiety disorders and depression. Anxiety and depression have overlapping symptoms and an estimated 40 percent of patients with depression also have anxiety." Dr Rathjen added.