Anavex Life Sciences Corp (AVXL)

[bebopagogo]

In the paper, memantine in combination with A-273 (and PRE-084, the other Sigma-1 agonist in the study) had reduced efficacy. The paper has results and analysis that shows a synergistic (more than just additive) improvement in efficacy of combo with donepezil. The study included isobologram analyses "performed according to Fraser's concept" and the combination index (CI) for the different combos was calculated from the results. A CI < 1 indicates synergy, C1 == 1 indicates additive behavior, and C1 > 1 indicates a negative effect (less than additive efficacy). The A-273 plus donepezil combo showed synergy for both measures of efficacy in the study. I think is more significant than an "obvious" additive effect that seems to be implied by the examiner's comments. One other note on the examiner's comments is that he mentions that both 2-73 and donepezil bind to muscarinic and sigma-1 receptors and thus have the same mechanism of action, but I didn't think donepezil binds to both?