Anavex Life Sciences Corp (AVXL)

[Investor2014]

Thanks Steady.

Not too many comments I can derive, at least not about inter-patient absorption variability.

10mg is enough to reach the > 4ng/ml concentration shown to be required for strong response to A2-73. However, the concentration level is short lived and maybe not long enough - on its own!

However, as Doc328 mentioned the A2-73 metabolite AV19-144 (which is therapeutic but I can't remember the reference) has lower max concentration level than A2-73, but much longer decay time and remain in the body for over 48 hours with a half-life of 8.56 h.

Interestingly in the PDD trial doses are just 10mg and 20mg, so perhaps the hypothesis being tested is that AV19-144 is particularly effective in that indication.

In AD it looks like at least 30mg will be required to maintain 4ng/ml for a few hours. Maybe we can guess that for some reason in AD A2-73 is doing the work and not so much AV19-144?

The tolerability, (Adverse Events) tracked in the healthy 18 - 55 year old P1 SAD cohort seems very similar to the AE reports from the P2a AD study. If we trust the tolerability statements from Anavex, mild and reversible headache etc., then 30mg and 50mg even in frail AD patients may be just fine. Also perhaps a lower dose twice a day could be an option. I would suggest that tolerability concerns as a factor limiting the use of A2-73 may be misplaced.