Anavex Life Sciences Corp (AVXL)

[falconer66a]

Simufilam, the SAVA drug, and blarcamesine.

Simufilam is a proprietary, small molecule (oral) drug that restores the normal shape and function of altered filamin A (FLNA), a scaffolding protein, in the brain. Altered FLNA in the brain disrupts the normal function of neurons, leading to Alzheimer’s pathology, neurodegeneration and neuroinflammation.

Cassava Sciences, Inc, (equity SAVA) has reported human clinical trial results showing that their drug showed efficacy in patients with Alzheimer's:
https://www.cassavasciences.com/news-releases/news-release-details/cassava-sciences-simufilam-improves-cognition-and-behavior

How does this compare to Anavex's blarcamesine? Particularly, how comparable are the mechanisms of action (MOAs) of each candidate Alzheimer's drug?

First, as I've detailed rather completely in a number of previous postings (some time ago), blarcamesine binds to and efficiently activates, restores the downstream modulating effects of the sigma-1 receptor protein. With this, among other propitious outcomes, proteins (enzymes) are properly folded and produced, allowing the normal functioning of neurons.

Simufilam, by some mechanism, is claimed to restore "normal shape and function of altered filamin A (FLNA), a scaffolding protein, in the brain." This, too, then restores, at least to some degree, normal neuron biochemistry. Well and good.

In consideration of both of these MOAs, I won't be liquidating any of my AVXL position to allow the taking of a new SAVA holding. Simufilam may eventually attain regulatory approval for Alzheimer's therapy. If so, very fine.

But it remains to be seen if the moderate symptomatic improvements of the drug can be sustained. Whatever caused the alteration of the filamin A (FLNA) protein is apparently unperturbed or not suppressed by the SAVA drug. It apparently fixes the FLNA protein after it's been altered. The drug's ability to chronically continue this as the Alzheimer's disease progresses in each individual patient remains to be seen.

Here's where blarcamesine, as I see it, is superior. Most likely, blarcamesine's sigma-1 receptor activation, which allows and promotes normalized protein folding, stops the initial, at the start alteration of the FLNA protein, thereby restoring normal neuron functioning. Blarcamesine changes things, favorably, "upstream," before they start, in this case before the FLNA protein ever gets altered.

Both drugs can apparently address the altered (dare I say, "misfolded") FLNA protein. Simufilam fixes it after it's been altered. Blarcamesine, most likely, prevents the alteration, before it becomes pathogenic. Therefore, it is likely to be continuously effective, at least in regard to the altered FLNA protein Alzheimer's etiology (causation).

Blarcamesine, most likely, prevents the formation of altered, dysfunctional FLNA proteins, before they might cause any problems. It keeps them from appearing. Simufilam tries to fix them after they've been formed and are active in the cell. Prevention, as opposed to continuing treatment of the continued production of the altered, pathogenic protein.