Anavex Life Sciences Corp (AVXL)

[Investor2014]

I think we may have had a similar discussion before. Here are some reminders, but I have no doubt you posses excellent evidence to the contrary.

A2-73 is a highly potent and selective allosteric M1 muscarinic and s1 receptor agonist.

from previous post

Not that it matters, but I did not have to pay $40 for access to the full paper.

You may have noticed that the paper is broadly spilt into two sections discussing the compounds in physiological (normal) and pathological (disease) conditions.

In short I do believe the ineffectiveness of A2-73 is only referring to physiological conditions in which one wants the compound to be inactive. Whereas, A2-73 is effective, and more so than other SR1 antagonist mentioned, in pathological conditions, which is where you want to agonise (correcting a typo in my original post) SR1 along with its Allosteric modulation of e.g. of M1.

The Missling Firetruck analogy that only leaves the fire station to do its work when there is a fire.

It would be rather odd for Tangui Maurice, who is an Anavex SAB member and proponent of A2-73, to write an entire paper concluding that A2-73 is the most ineffective compound.

AF710B, a Novel M1/s1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease
What you need to know is in the title and extensively discussed in the paper.
Note that A2-73 was previously known as AF710B.

Abstract
We previously developed orthosteric M1 muscarinic agonists (e.g. AF102B, AF267B and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and s1 receptor agonist. AF710B exhibits an allosteric agonistic profile on the M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (p-ERK1/2, p-CREB). AF710B (1–30 µg/kg, p.o.)

NEW YORK, NY – March 23, 2015

“With the newly presented data we are very encouraged to have ANAVEX 2-73 currently in the clinic and are looking forward to provide an update on the progress of the trial next quarter. The new drug ANAVEX 3-71 indicates extensive therapeutic advantages in Alzheimer’s and other protein-aggregation-related diseases given its ability to enhance neuroprotection and cognition via sigma-1 receptor activation and M1 muscarinic allosteric modulation,”