Anavex Life Sciences Corp (AVXL)

[Investor2014]

I suppose it was a slightly leading question, so I found this:

In summary, the complex structure of the CNS makes brain penetration a very complex feature which cannot be rationalised on the basis of any single parameter. Although total brain concentrations are still the most common measure of CNS exposure, it is now emerging that they are more of an indication of high non-specific binding to brain tissue rather than being pharmacologically relevant. Neither total brain levels nor BBB permeability can be taken without considering the binding capacity of the brain tissue when a link between exposure and efficacy is needed. The current paradigm of brain penetration therefore is changing towards a more compartmentalised view which allows to better rationalise the distribution of compounds within the brain and makes use of brain compartments which are more relevant pharmacological effects. The holistic concept of CNS penetration considers rate of permeation across the BBB, extent of brain penetration and the intra-brain distribution of a CNS drug as distinct but interrelated properties of a CNS drug which have to be determined by different in vitro and in vivo methods (Reichel 2009). Therefore, the integration of data from various assays and studies is becoming a central part of the evolving paradigm in order to develop quantitative relationships between dose, exposure and efficacy. By integrating these data and technologies into PK/PD modeling and simulations it will be possible to generate a working understanding of the pharmacokinetics and pharmacodynamics of potential drug candidates in the human CNS. Such an understanding will be paramount to define PK parameters which are favourable for the desired indication, to guide the preclinical development of the compound (e.g. dose selection for toxicity testing in higher species as well as first-in-man and therapeutic doses) and ultimately to increase the chances for a successful phase II study in human patients.

http://www.frontiersin.org/10.3389/conf.fphar.2010.02.00028/event_abstract

Guess our's is no ordinary PK/PD analysis, so could also contribute to the wait.