Replies to post #176149 on Anavex Life Sciences Corp (AVXL)

[XenaLives]

How about the fact that it seems to work and the others don't?

P2a had unexpected efficacy.

The three trials going on now should be final proof of concept.

[Investor2014]

AVXL has described cellular homeostasis as a general S1R agonist function. They have never given any credible reason to expect an advantage of 2-73 over other agonists.

It isn't so simple.

Different S1R agonist molecules are not guaranteed to have same therapeutic potential, a debate that goes on ad nauseam - probably because the science remains complicated and few studies to date have been conducted in humans. DPZ for example was not studied or approved because of its S1R agnostic properties, but research is beginning to show that indeed the DPZ S1R binding could be responsible at least in part for what little efficacy the drug appears to have.

This is further complicated by a molecule's other and different activation sites e.g. for A2-73 muscarinic modulation. There is research, which I have already referenced, that proposes a synergy between A2-73 and other drugs e.g. DPZ in low doses precisely because the potential adjuvenant therapeutic potential of combined drug action. In an appropriate dosage ratio the binding to S1R of the two drugs may distribute among receptors to achieve a desired efficacy of agonising Sigma-1 receptors alongside other mechanism whether fully understood or not.

Several research papers points out that there is now a body of evidence pointing to the therapeutic potential of S1R agonism and muscarinic modulation.

I am sure you are able to find the available research on A2-73 and its proposed MOA thesis, probably near all them have at one time or other been posted here.

In the end these open questions are key to the risk/reward ratio. If you know or strongly feel you know the answer, then you must must take the appropriate side of the long vs. short trade.