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Good scrutiny and understanding of Anavex science.
The Anavex record; and future.
I just checked my records, to see when I bought my first Anavex Life Science Corp shares; May 2016. In the following years I’ve continued to buy more, when I have some discretionary budget dollars.
Now, for over six years, I’ve closely followed and scrutinized the particular (even peculiar) science of the Anavex molecules, trying to determine if it’s legitimate. Can blarcamesine (Anavex 2-72) really provide the multitude of therapeutic benefits imputed to it? Safely, without side effects?
All of that depends on just how the molecule works in cells. Until the last two years or so, how (or if) blarcamesine can work to resolve any of the central nervous system (CNS) diseases Anavex is targeting was legitimately questioned. The molecule’s “MOA,” mechanism of action, was both unknown and questioned. The early preclinical therapeutic results, in both murines (lab rodents) and humans were simply too good to be true. Too many things got fixed (or prevented), without any expected side effects. Virtually all drugs acting powerfully in the CNS have untoward side effects. None of those with blarcamesine.
Again, too good to be true.
But in the last two years or so the various mechanisms of action of blarcamesine in cells, in neurons in particular, have been discovered and elucidated. A number of detailed, definitive papers have been (independently) published, showing how this single small molecule is able to modulate, promote, and restore a diversity of cell processes, bringing functional health to the neurons and the tissues and organs they control.
Here’s the important fact, being evermore substantiated in both murine and human trials, in vitro (in isolated cells in glassware) and in vivo (in living organisms, murines and humans). So far, it has been discovered that blarcamesine, when attached as a ligand to the sigma-1 receptor protein in neurons, causes, facilitates a wide diversity of “downstream” processes in the cell; many of which are “cell-keeping” (homeostatic) processes. With restored or modulated homeostasis, cells, especially neurons, can function normally. Diseases and conditions are obviated. Health is restored or promoted.
But this is the even greater fact. Simply, just how many diseases and conditions can be either fixed or prevented by blarcamesine’s activation of the sigma-1 receptor protein is not yet known. It is becoming ever more clear that propitious activation of the sigma-1 receptor is not a fix for just three CNS diseases. It favorably modulates just a host of downstream chemical reaction cascades and processes that provide health to both cells and organs.
The prediction is this. Sigma-1 receptor activation biology will continue to be investigated and elucidated. Sigma-1 receptor activation biology is a new Big Thing; previously unrecognized.
Some have castigated Anavex’s long list of “pipeline” diseases blarcamesine might treat (or prevent). Too good to be true. No small molecule (molecular weight 281) can possibly have so many modulating or controlling effects within a cell.
Let’s watch. Continued investigations of the molecule almost surely will discover even more things it controls or modulates. Blarcamesine (and its analogues Anavex owns) is destined to be a major, even revolutionizing therapeutic in coming years. First with Rett syndrome, Parkinson’s disease dementia, and Alzheimer’s. But after that, a widening diversity of human (and veterinary) diseases and conditions. By the end of the 2020s, medicine will not be the same. Nor will human health.
For the consideration by all, we welcome contrary posts, telling specifically why little or none of what I’ve conjectured can or will occur. Let’s see the contrary Anavex science. Lay it out for us, please.
Best time to sell AVXL.
Advice; well taken.
Correct. There will be no competition.
Unaffordable, at both prices.
If Biogen has cut the annual price of Aduhelm by half, from $56,000 down to a mere $28,000, it means nothing, other than the original price was way too high by itself. Functionally, there is no effective difference for an Alzheimer's drug that costs either $56k or $28k for a year's treatment; in both cases it can't be afforded.
The next reality will be when Biogen, in desperation, cuts the price to $10,000 a year. Somewhat affordable. But side effects (brain bleeding, etc.) and poor resolution of dementia will, finally, kill the drug.
Another drug development story to be read by people working on their masters of business administration (MBA) degrees. It will contrast with the Anavex story, to be written in 2022.
My error. Yes, thank you; later, 2023 for the Alzheimer's results. Will take some time after that (months? years?) for the FDA to act.
But Rett results are forthcoming. They will adequately substantiate the unique mechanism of action (MOA), acting propitiously against a CNS disease. Rett results will portend the same for Parkinson's disease dementia and Alzheimer's. Blarcamesine efficacy and safety data will no longer be based on lab rat results. It will be the drug acting favorably in real humans with a real, otherwise recalcitrant central nervous system disease. Anavex and blarcamesine "maybe's" will become "very likely's."
The "market," in its great wisdom, will respond. A few market players, even, might recall seeing the numbers I just posted --- or, will punch their own.
Later?
That $1600 price projection....
The Anavex waiting game.
For those considering investing in some Anavex Life Sciences Corp shares some ‘DD,’ is in order commonly called “due diligence.” (I think the better term is determining diligence.)
What, then, is being determined? Primarily, can the company ever make any money, so as to increase the share price. Right now (as for many years) the company is a biotech start-up, having no sales revenues. It has only some unproven, unapproved, patent-protected new drugs, which are aimed at several otherwise recalcitrant central nervous system diseases. Is this the place to put one’s major investment dollars?
That, of course, based upon one’s determining diligence, is something each investor must decide upon. But even new, inexperienced stock investors must quickly realize all of the various factors and outcomes that must fall into place for small drug start-ups like Anavex. Is it any wonder that the Anavex share price has not increased to any large figure? Right now, there’s nothing to cause that. And, until solid, positive clinical results are released, from which it could be reasonably anticipated that the FDA would approve the Anavex drug, there can be no AVXL share price ascent.
Of course, those of us who, over the years, have accumulated and held an AVXL position see things that will most likely bring about the expected clinical results, which will then prompt FDA approval. After that, there will be no mysteries. Blarcamesine works against at least one (but probably three) CNS diseases. Consequent FDA approval will allow large sales of blarcamesine, bringing to the company continuing and ever-expanding new revenue streams.
So, what is the information and data that support our confidence in the company’s eventual success? To explain that in any detail would require hundreds of pages. Instead, simply study all of the information presented on the company’s website. Read (and try to comprehend) everything. In summary, all pre-clinical data for the company’s drug, blarcamesine (aka Anavex 2-73) are profoundly positive. It has mechanisms of action (MOAs) in neurons and other cells that fix a diversity of pathologies. Too good to be true, it would seem.
If that is one’s perception, don’t take an AVXL position until the clinical results appear; or, even more safely wait until the FDA approves the drug. But those of us here, who have scrutinized, trusted, and understood all of the existing scientific data on blarcamesine, have taken AVXL positions of various sizes. In our many years we’ve seen nothing emerge that questions or negates the powerful Anavex science.
We will continue to read and consider the various postings telling why the AVXL share price will vary in either direction. But nothing significant will happen until the clinical results from the Rett syndrome trial, the Parkinson’s disease dementia trial, and later the Alzheimer’s disease trials appear. When any of that happens, starting in some time in 2022, the medical world will be changed. Gonna be interesting to watch; especially for those of us who “got in” early with our AVXL purchases.
But we Anavex longs aren’t dumb. We will continue to search for and consider any negative news or science that emerges. So far, there has absolutely none. Corporate announcements have been later or more delayed than many would have wished. Such is the game of new drug development. Slower and more deliberate than wished. But patience will be rewarded. During these extended times awaiting clinical results the molecular biology of blarcamesine has not changed. Girls with Rett syndrome, taking blarcamesine in the clinical trial continue to yield accumulating therapeutic results. Those won’t evaporate if the trial continues longer than the “we want to know NOW” crowd would prefer.
A year from now, heading into 2023, things for Anavex shareholders, and for patients with targeted CNS diseases will be very different. Worth patiently waiting for.
If it’s ‘not FDA approved’....
The GABA problem.
Ah, blarcamesine has already been tested.
Thank you very much for this information, showing that early tests of blarcamesine (Anavex 2-73) have already been conducted on ALS animal models, successfully.
My conjecture is now a bit more firm. If I had ALS I'd be petitioning an ALS support association to encourage and underwrite human trials. But I have a different CNS disease, hereditary spastic paraplegia (HSP), making my legs stiff. Have to use a walker to amble about.
In that regard (HSP) I noted that the girls with Rett, in the first safety and tolerability trials of blarcamesine, showed that one outcome of blarcamesine therapy (even at low doses) was the markedly increased production of GABA, gamma-aminobutyric acid. GABA is deficient in the long motor neurons that control the muscles in my legs, allowing the nerves to continually fire; causing the spasticity. I'm so eager to participate in a clinical trial of blarcamesine for those of us with HSP. I'm certain that it will be therapeutic.
But before I petition the HSP support group, I'll wait for the results from the full Rett clinical trial. Those results will reveal the improved GABA factor. Everyone who understands the GABA-deficient pathology of HSP will instantly desire to start taking or allow blarcamesine. HSP is one of a number of hidden rare diseases for which blarcamesine will be profoundly therapeutic.
A distant but viable conjecture—ALS.
Ok, this is entirely conjectural; should not be a factor in considering the holding or purchase of AVXL shares. But most science begins with well-formed conjectures, which are then tested. What I describe below may, someday, be tested, with blarcamesine or another Anavex sigma-1 receptor activator.
Just read a research report that showed that the accumulation of specific waste or toxic proteins in the axons of nerve cells with amyotrophic lateral sclerosis (ALS) cause the disease symptoms. The paper claimed, “Clearance of axonal TDP-43 or dissociation of G3BP1 condensates restored local translation and resolved TDP-43-derived toxicity in both axons and NMJs. ... Clearance of axonal TDP-43 or dissociation of G3BP1 condensates restored local translation and resolved TDP-43-derived toxicity in both axons and NMJs.”
https://pubmed.ncbi.nlm.nih.gov/34824257/
Simply, if nerve cells can clear, remove the toxic proteins, the ALS (“ Lou Gehrig's Disease”) is resolved; a cure, dare I say.
Might it be that for those of us who do not have Lou Gehrig’s disease our nerves normally and continually clear away the toxic proteins? With this normal autophagy our nerves work properly. But, for some reason (genetic, chemically-induced, etc.), this normal autophagy fails in the neurons of those with ALS.
Might ALS be caused by a specific failure of normal autophagy? Moreover, might blarcamesine’s ability to restore autophagic processes in diseased cells be a treatment or cure for the disease?
That conjecture can’t be known until a lot of detailed, precise work is done. I note that there are mice that are animal models of amyotrophic lateral sclerosis (ALS). Won’t be inordinately expensive to test various dosages and treatment regimens of blarcamesine on them, to see if the diseased mice respond in any positive way. If they do, human trials would be next.
Again, the strength (not magic) of blarcamesine centers on its unique ability to favorably activate the sigma-1 receptor protein’s ability to modulate autophagy, thereby restoring healthful, normal homeostasis within the diseased neuron.
Once again, disrupted autophagy causes Alzheimer’s.
Anavex nonsense; or science?
Thanks, everyone. A great collective effort.
Side effects (from previous URL)
Here is a listing of side effects of dextromethorphan:
Side effects.
Dextromethorphan is used for sleep problems. But given its side effects blarcamesine (which has very few and are mild and transient) will beat it.
https://www.drugs.com/sfx/dextromethorphan-side-effects.html
A prescription drug; and for sleep.
Then, beyond Alzheimer’s.
How blarcamesine gets approved is yet unknown.
Complications to the North, and Down Under.
What happens if the FDA fails to approve blarcamesine, after statistically significant data from any of the three clinical trials appear, showing both safety and efficacy?
Well, of course, because the professionals at the FDA are that, medical professionals, we can be assured that their decisions have been and will be based solely on sound, statistically significant clinical data (as in the manner of Biogen’s Aduhelm (cough)). We can be assured, pecuniary (money-making) factors won’t play any significant roles in drug approvals or therapeutic usages.
However, if nefarious, extraneous monetary factors somehow work their ways into the FDA’s disapproval of blarcamesine (Who could imagine?) and the drug fails to be allowed on American pharmacy shelves, the matter will not be domestically resolved.
Prescription drugs are sold in most of the world’s countries; not just the US. Will the Australians’ FDA, their Therapeutic Goods Administration, also be controlled or manipulated by Big Pharma stakeholders and likewise nix any use of blarcamesine Down Under — after the profoundly safe and favorable clinical results appear?
Might Australian bureaucrats punch the numbers of the costs of caring for ever larger numbers of Alzheimer’s and Parkinson’s patients each year, plugging in the tax-dollar savings that blarcamesine would annually and continually yield?
As powerfully brilliant and supremely knowledgeable as the FDA pooh-bahs are, even after being “taken to lunch” by Big Pharma lobbyists, they don’t control what drugs are allowed on the shelves of drugstores in other countries. Like the Aussies, our Canadian friends might well “interpret” the Anavex clinical trials data “differently.”
How will things play out when people with severe CNS diseases, in other countries, gain either disease prophylaxis or resolution, while Americans continue to suffer the lethal outcomes of the existing FDA-approved CNS drugs? Aussies or Canadians get substantial relief from Parkinson’s and Alzheimer’s. Americans don’t. How might all of that play out, politically, in the US?
“Well, as President of the US I have the greatest confidence in my experts at the FDA. They have the right information, have made the right decisions. I rely on what they say. They know best.”
Sure.
MOA Validations
I contend that in addition to the side effects differentiation of Anavex over Acadia, a powerful driver of the Anavex drug, first for Rett, then for the other CNS indications being targeted (being tested in clinical trials) will be blarcamesine's mechanism of actions (MOA).
If the Acadia drug gains approval for the treatment of Rett syndrome, will that approval tend to validate any other Acadia drugs or indications? Is the MOA of the Acadia drug applicable by extension to any other diseases? I see no evidence of such.
But when blarcamesine (Anavex 2-73) gains FDA approval for Rett therapy, its unique MOA (propitious activation of the sigma-1 receptor protein) will be recognized and clinically demonstrated. With that, it will be understood how it then, by the same MOA, can be therapeutic for other CNS diseases.
For both drugs, validation of the MOA will be important. For Anavex, it will validate potential therapies for other CNS diseases. Two of those are in clinical trial, Parkinson's disease dementia, and Alzheimer's. With the safety and therapeutic success against Rett syndrome, clinical successes demonstrated in the other two trials will be ever more sound. Approval for them should be forthcoming.
We’ll be taxed for Aduhelm
Anavex and Autism
More work showing sigma-1 receptor disease involvement.
A new paper in the Journal of Biological Chemistry describes detailed work characterizing the deep biochemistry of the sigma-1 receptor protein:
https://www.jbc.org/article/S0021-9258(21)01105-4/fulltext
It's now an error to presume that sigma-1 receptor biochemistry is either mysterious, difficult to discover, or inconsequential. A few years ago, those perspectives would have been valid. No longer. The central roles of the sigma-1 receptor protein, in modulating and facilitating a diversity of cellular processes are becoming ever more apparent.
An author of the paper, in a separate article stated the following: https://www.eurekalert.org/news-releases/936633
I'm up, too.
I was wrong.
Well, not an Anavex matter.
An Anavex molecule for ALS.
Blarcamesine induction of pan-viral destruction.
In drug development, observations don’t count.
Actual Anavex science will be secondary.
Looking out to an Anavex future.
Thanks for those corrections. I didn’t closely determine the Microsoft share price over the years. But, anyone who took an early equity position (and held it), today has some very handsome value gains. Back then (early ‘90s), had I known, I’da scraped up $1000 and bought in. But, I didn’t. Nothing for me to talk about (regarding Microsoft).
The question here is whether or not Anavex will yield big gains in the coming years. I knew very little about computers, computing, or potential share prices for the new companies leading the new technologies. Not so with Anavex. I’m an accomplished, knowledgeable biologist; can understand the arcane complexities of both general cell biology (taught it to talented students in a very select college-preparatory program; where my students went on to gain science scholarships and earn advanced degrees), and the particular, unique medical biology of the Anavex molecules. With those understandings, I’m confident in the eventual success of my modest Anavex investment.
If Anavex gains regulatory approval to sell blarcamesine to treat but any one of the three CNS diseases currently targeted, Rett syndrome, Parkinson’s disease dementia, or (the real biggie) Alzheimer’s disease, the AVXL share price will increase by an order of magnitude (10X) or more.
But there is the real possibility, pending eventual clinical-trial affirmation, that the Anavex molecules will be able to treat or prevent any number of other neurodegenerative or geriatric (age-related) diseases. Of particular impact will be the discovery that blarcamesine (or Anavex 3-71) produces profound prophylactic, disease-prevention outcomes. As Dr. Missling, Anavex CEO has already mentioned, there is the possibility that someday mass numbers of people will take a tablet of an Anavex drug each day, to ward off untoward aging or geriatric diseases. When everyone at the age of, say, forty needs to start popping an Anavex pill with breakfast each day, one or two more zeros will be needed to indicate the AVXL share price.
Then, finally, there is the distinct possibility that an Anavex molecule, by its propitious modulation of chromatin functions in chromosomes would markedly reduce mutations in germ cells (ova and spermatozoa). Were that the case, males would take the Anavex drug before fathering children. Women, because the genetics of ova are determined at a very early age, even before birth, would have to take the drug during their entire lives; to minimize genetic defects in first her ova, then in the children those would produce.
All of this will need to be properly determined and demonstrated. Many clinical trials on the Anavex horizon.
And I remember Microsoft, Apple, etc.
Here's what Schwab says.
As suggested by Tom, I clicked on the "B" icon on my Schwab account, and got this:
Schwab says trading halted.
Yep, checked my Schwab account. At 5:25 EST said trading halted for AVXL.
I'm keeping my moderate AVXL position; don't intend to sell and shares for a good number of years. But like everyone else, will be interested to learn who, why, and/or how trading was terminated.
Anyone want to fill us in on this? Who has the authority to stop trading? For what purpose? Then, when and how does trading resume? Who makes that decision?
Is this weird, or what?
COVID-19, autophagy, and the aging process.
The discovery (in the previously referenced study; paper) that the SARS-CoV-2 virus is able to disrupt normal autophagy processes in cells, thereby disrupting the cells’ ability to consume or destroy those viruses might help explain why COVID-19 in children is seldom severe, whereas in the elderly it so often is. With aging, many processes diminish. Diminished autophagy is a recognized feature of aging:
Blarcamesine could stop COVID-19? A mechanism?