Replies to post #260292 on Anavex Life Sciences Corp (AVXL)

[Investor2014]

Imo it seems pretty clear the approach Anavex have taken is a design of the current P2 trials to verify their precision medicine approach and then optimise pivotal trials for higher probability of success.

[sokol]

Boi:

Thank you for your post. I agree that not all sigma-1 agonists are the same. I add this in support:

Donepezil is a nonselective sigma-1 agonist as opposed to a sigma-1 receptor selective medication such as AVXL 2-73. Selective sigma-1 agonists show promise for treating dementia and other conditions.

"Although no sigma-1 receptor–selective medications are currently approved by the FDA, several currently marketed agents and other substances interact with sigma-1 receptors in a nonselective manner, such as fluvoxamine, donepezil, haloperidol, and pentazocine.".....

ANAVEX2-73: The leading sigma-1 agonist under development is ANAVEX2-73, an amino-tetrahydrofuran derivative and mixed muscarinic/sigma-1 receptor agonist.16 At present, 3 active clinical trials involve ANAVEX2-73: one for Parkinson disease with dementia and 2 for Alzheimer disease.17 Another clinical trial for Rett syndrome is planned, announced in October 2018 by manufacturer Anavex Life Sciences."...

https://www.neurologylive.com/journals/neurologylive/2019/april-2019/sigma1-agonists-offer-combination-approach-to-dementia-symptoms

"ANAVEX 2-73 (AV2-73) is a novel cholinergic and selective sigma-1 receptor agonist under development as potential agent for Alzheimer’s disease or dementia with neuroprotective properties. "

https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/2321147

It seems to me, very much a non-expert, that comparing selective sigma-1 agonists with non-selective sigma-1 agonists is an apples/oranges comparison.

Furthermore, AVXL 2-73 “... it is a mixed ligand for sigma1/muscarinic receptors...”, and that needs to be kept in mind in making comparisons.

[tootalljones]

well written, well thought post.

[JWC3]

The answer that Dr M gave to this question was that mere agonizing of Sigma-1 was only a polarity indication. The real effect is how well the agonizing ligand “activates” the receptor!!!! Activation is the key!

[frrol]

He might have, but keep in mind that drug trials are, literally, trial and error. A lot of planning goes into them, and a lot of feeling in the dark along the way. Doc's points are valid and he believes that objectively speaking the PDD trial is less likely than others to show results for its primary endpoint. So why would the company do such a trial? Because they feel there is a reasonable chance it could succeed. Why that endpoint? Because it is a common one for PDD.

Biotech is risky and we are no exception. This certainly is no magic Wonka ticket.