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Different, but effective.
Thank you. Good idea. In the comments section I just posted this note:
Gotta have the right molecules.
Really? Anavex has no trade secrets?
The Blarcamesine Anti-aging Factor
Just read a new article in the October The Scientist, “a magazine for life science professionals,” entitled "Accurate Protein Production Promotes Longevity." Very important for Anavex science.
The article summarized this paper in Cell Metabolism:
https://www.sciencedirect.com/science/article/pii/S1550413121004174?via%3Dihub
The Scientist article stated, “As an organism ages, the efficiency and accuracy of its cellular processes deteriorate. For example, protein production, folding, and degradation all decline in quality, such that loss of protein homeostasis (proteostasis), is ‘a major hallmark of aging’ and age-related diseases, says molecular biologist Patricija van Oosten-Hawle of the University of Leeds....”
For Anavex, the important matter is this. Both of the Anavex sigma-1 receptor agonists (activators), blarcamesine (Anavex 2-73) and Anavex 3-71, restore or promote proper protein synthesis and, especially, protein folding. Misfolded proteins, usually in the proteins of reaction-controlling enzymes, are the source of a host of aging and neurodegenerative diseases; causing dementia and other neurological dysfunctions.
The potential take-away? The Anavex molecules very likely will slow, stop, or reverse various aging processes occurring in the central nervous system; and, perhaps in other body systems.
Will blarcamesine be the first, effective Ponce de León Effect drug, usefully and safely preserving or restoring youthful functions and processes in aging humans?
As I've contended before, Anavex has most likely already checked this with Caenorhabditis elegans, a common, well-characterized lab roundworm used in aging studies. The time is not yet appropriate for Dr. Missling to lay out what Anavex knows about blarcamesine working its anti-aging processes in lab roundworms. For the nonce, I'll take the criticisms. Dr. Missling can announce the findings of his studies after it is recognized that blarcamesine really does work in two or three big CNS diseases in humans, next year.
From Rett, on to other autisms.
No ‘magic.’ Just a powerful, unique MOA.
Is there a “competition” factor with blarcamesine?
Missling, prophylaxis, and the Anavex trifecta.
Today’s revenue projections probably way too small.
After Missling’s conjecture on what a year’s treatment with blarcamesine in girls with Rett syndrome will cost (six figures), there have been a good number of postings extrapolating those numbers, in some way, on to revenues eventually from the other two Anavex CNS disease targets, Parkinson’s disease dementia, and Alzheimer’s. Well and good. But very likely all of them, in say five years or so, will prove entirely wrong.
From the company’s list of pipeline drugs and diseases, in addition to the present three CNS diseases, there are: Parkinson's Disease, Infantile Spasms, Angelman Syndrome, an undisclosed rare disease, Frontotemporal Dementia, Depression, Stroke, Visceral Pain, and Acute & Neuropathic Pain. Previously, elsewhere, there have tangential references to treatments or prevention of cardiovascular diseases and cancers.
https://www.anavex.com/therapeutic-candidates
How would corporate revenues be affected if, say, only a few of these others gain approval for the use of an Anavex drug?
But perhaps the biggest source of continuing revenues will result from the discovery that patients taking any of the Anavex drugs get relief from other geriatric diseases. People taking blarcamesine for their Alzheimer’s get relief; have normalized cognition, etc. But at the same time it’s discovered that they have far lower rates of cardiovascular disease or cancers. Consequently, blarcamesine gets prescribed as a geriatric disease prophylactic, preventative. Everyone, starting in their forties, starts taking one or two Anavex pills a week, for the rest of their lives.
With other new diseases, and Anavex prophylaxis, add a few more zeros to the annual revenues metric.
When retail investors learn the story.
Blarcamesine treatment cost projections.
With those projected annual Rett syndrome treatment costs (revenues to Anavex), pull up your spreadsheet and start punching in numbers that might then apply for both Parkinson’s disease dementia and Alzheimer’s.
Lots of zeros.
A few of us with conservative cost projections have punched in projected $10/day blarcamesine costs for the millions with Alzheimer’s. Should we, now, increase that daily treatment cost?
Oh, wait. Missling’s telling of projected annual blarcamesine/Rett treatment costs (6 figures) must mean that the Parkinson’s disease dementia and Alzheimer’s trials are failing. Data won’t be good enough to get FDA approval. Therefore, Anavex will have to survive only on Rett revenues. [Sarc]
The big question for Anavex.
The only thing that really matters to Anavex Life Sciences Corp, and its shareholders, is the eventual ability to sell blarcamesine somewhere in the world, for some recognized or authorized therapeutic protocol. The intellectual jousting we engage in here are both sophomoric and irrelevant.
Sales of the drug first requires sales and use approval from some country’s drug regulatory agency; which most likely will be first with the US FDA or the Australian TGA (Therapeutic Goods Administration). With that, Anavex gains operating revenues; becomes a functioning pharmaceutical company.
But approval by the FDA or TGA requires the presentation of positive human clinical trial data confirming both safety and efficacy. Data and findings from murine studies from any number other drugs acting putatively in the manner of the Anavex molecules will be utterly disregarded; won’t even be submitted. For approval of blarcamesine, murine studies are irrelevant. Only human data from properly-conducted trials are considered.
Other drugs, however, will enter into the sales and use approval decision-making process. To be approved, a new drug must show not only safety and efficacy, but also match or exceed the existing standard of care (SOC) drugs for the targeted diseases or conditions. For Alzheimer’s, there are a few being prescribed. The Anavex drug, in the large, definitive clinical trial (now under way) will have to show that it matches or exceeds the data for Aricept (donepezil), the presently most-prescribed drug to treat Alzheimer’s.
How will blarcamesine’s therapeutic data compare to those of Aricept? Look it up. Aricept works, but only to a degree, and only for a short or moderate period. It has the ability to slow the progression of Alzheimer’s symptoms, but only for a period. Eventually, the drug fails to work, symptoms progress lethally.
When the definitive blarcamesine-against-Alzheimer’s trial ends (some time next year), will it prove better or worse than Aricept? I maintain my AVXL position based upon all of the both murine and human trials data. Not a scintilla of evidence that it will turn out worse than Aricept; quite the opposite.
My error. But PRE-084 still produces amyloid-beta.
Wrong term.
Please tell, how is this Anavex negative?
Here’s the study’s S1R-agonist.
Ok, as a competent reviewer of research should do, I pulled up the actual paper telling the research:
https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00473-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124721004733%3Fshowall%3Dtrue
Those who wish are welcome to scrutinize the presented information. Lots of it. The sigma-1 receptor agonist in the study was “PRE-084.” Information on this molecule here:
https://www.selleckchem.com/products/pre-084-hydrochloride.html
Ok, then, did the paper show that activation of the sigma-1 receptor actually caused the production of amyloid wastes, which cause Alzheimer’s. Yes, it did—with the PRE-084 molecule. (For those discounting murine [lab rodent] research, read no further. All of this was in mice.)
So, now pretty clear. Merely getting some molecule to stick to the sigma-1 receptor protein, thereby “activating’ it in some way, does not necessarily, in every case produce good therapeutic results. A few sigma-1 receptor agonists, those of Anavex, do. Others do not.
The take-home message is this, confirmed by this (and other) studies. To prevent the production or accumulation of amyloid beta wastes in neurons, to prevent or treat Alzheimer’s, the sigma-1 receptor protein must function normally and completely. Disrupting that function with a ligand (attached molecule) with a toxic “activator” allows the production of amyloid beta wastes. Facilitating sigma-1 receptor function with the Anavex molecules produces favorable therapeutic outcomes. In reality, this research further substantiates the unique, propitious Anavex mechanism of action (MOA) at the sigma-1 receptor protein.
As the human clinical results will show, Anavex has it.
The fellow’s “activator” was actually toxic.
Actually, the finding that the author’s particular sigma-1 receptor ligand caused the production of amyloid beta proteins, which cause Alzheimer’s symptoms, is actually a confirmation of the mechanism of action (MOA) of the Anavex molecules, blarcamesine and Anavex 3-71.
Again, the good fellow failed to tell the specific sigma-1 receptor ligand he used. It surely wasn’t either of the Anavex molecules. He did claim that his molecule “activated” the sigma-1 receptor protein. But, so clearly, not in the same way. In effect, it disabled the receptor, keeping it from favorably modulating the protein’s several downstream biochemical outcomes. The fellow’s molecule (whatever it was) disrupted the normal function of the sigma-1 receptor protein. It was toxic. Hence, amyloid beta was produced.
This rather clearly proves that if sigma-1 receptor activity is disrupted, shut down, or diverted, amyloid wastes are produced or are not cleared; Alzheimer’s symptoms are generated.
The Anavex molecules have a propitious MOA at the sigma-1 receptor protein. Other sigma-1 receptor ligands have the opposite result. To treat (or prevent) Alzheimer’s, the sigma-1 receptor protein must function fully and favorably. Anavex has the molecules that facilitate this. Other sigma-1 receptor ligands fail.
Pharmacologically, Anavex has the winning molecular hand.
Crucial info not provided. Ignorance, or intention?
Ok, the good doctor’s research discovered this: “Conversely, a drug that activated S1R triggered an increase in beta secretase cleavage of palAPP and increased production of amyloid beta in axons.”
Not good, at all. A-beta in axons causes Alzheimer’s symptoms. And, according to this statement, activation of the sigma-1 receptor protein produced amyloid beta.
Who’s got it right? Anavex, whose sigma-1 receptor activator, blarcamesine, in human trials, reduces the symptoms caused by amyloid beta; or, this researcher, whose particular sigma-1 activator—whatever it was—did just the reverse?
Key is this. Any number of molecules can be sigma-1 receptor ligands, having the ability to bind to that molecule and thereby change its biochemical functions. Some, such as blarcamesine and Anavex 3-71, after binding to the sigma-1 receptor, produce propitious (favorable) downstream outcomes. Pretty clear, the particular molecule used in the author’s study clearly complicated, suppressed the normal, favorable mechanisms of the sigma-1 receptor protein.
Might it be curious that the sigma-1 receptor ligand used in the study, which produced results exactly opposite to the Anavex molecules, was not identified? Could it be supposed that the researcher, working with the sigma-1 receptor protein, should be aware of the Anavex science centered on that protein; and the two Anavex molecules that produce results exactly opposite to his? Is the man merely ignorant (failing to scrutinize all relevant sigma-1 science, for which Anavex leads the way)? Or, for convenience to his purposes (whatever they are) has he deliberately failed to mention the Anavex successes, while at the same time deliberately failing to simply tell the name of his sigma-1 ligand?
Inquiring minds wish to know.
Informed, knowledgeable minds already know of blarcamesine’s successes, which do not in any way increase amyloid beta production; just the opposite. For Anavex, the “research” is irrelevant.
Not likely to be adjunct disease trials.
The efficacy of blarcamesine against SARS-Cov-2 (the virus) and COVID-19 (the disease) won’t be demonstrated in deliberate human clinical trials. Same for the other very positive therapeutic outcomes produced by the molecule, such as suppression of insomnia, antineoplastic outcomes (anti-cancer), cardiovascular system improvements, etc. All of that would be expensive and very time-consuming.
Instead, get the drug approved for two big CNS diseases, Parkinson’s disease dementia and Alzheimer’s, then let the millions suffering from those CNS diseases start taking blarcamesine. Then, simply tally (statistically assess) the occurrence of those other diseases in people taking blarcamesine, compared to statistically-valid parallel groups not taking the drug. What happens when it is discovered that people taking blarcamesine get degrees of relief for the CNS diseases targeted for them, but at the same time other positive health benefits appear? People on the drug sleep healthfully; no insomnia. COVID-19 cases are fewer and/or less severe.
Detailed analyses of people taking blarcamesine for CNS diseases will reveal other associated, commensurate positive outcomes — which will obviously occur in people taking blarcamesine without any CNS condition.
Share owners smart.
Again, as always before, blarcamesine is safe.
https://www.anavex.com/post/data-review-by-the-independent-dsmb-reported-for-phase-2b-3-trial-of-anavex-2-73-for-ad
Today’s announcement is but another, of many, showing that blarcamesine is safe when used to treat humans. In no trial, murine or human, pre-clinical or clinical, has blarcamesine ever exhibited adverse events (side effects) of any severity.
Understand, this is extremely significant. Think not? Try to list out all of the known side effects mentioned in TV ads for any drug acting in the central nervous system. You won’t be able to write them down fast enough. You’ll also wonder if anyone should actually take the drug, as the side effects appear as bad as the symptoms it’s supposed to suppress.
To be approved for sales and therapeutic uses a new drug must prove two things: a) it’s safe; does not cause disqualifying or severe side effects, and b) it’s effective, it sufficiently reduces or prevents disease symptoms. Anavex, for blarcamesine, has the drug safety issue nailed. Only thing left are the clinical efficacy results from the three trials, to appear in coming weeks and months. They, too, will be positive.
Blarcamesine for cardiac conditions?
I, too, saw this PubMed paper, telling how a Chinese herb mixture, called Yiqi Huoxue, produced cardioprotective results in rats. Could this happen in humans? Very likely.
From the paper’s abstract:
‘Biomarkers’ and therapeutic efficacies.
Understandably, a frequent topic has been ‘biomarkers,’ as they might indicate therapeutic efficacies of certain drugs, or the presence of actual disease conditions, etc.
What, actually, constitutes a ‘biomarker?’ What is a biomarker? Here’s where the FDA defines it: https://www.fda.gov/drugs/biomarker-qualification-program/about-biomarkers-and-qualification
Specifically:
Not appropriate.
Lower prices will work for me.
Persisting Accumulation
ALPP closed today, at the high of the day, $3.95, a day's gain of 14.16%.
The buying pressure continues; without any corporate announcements, news, or other clear buying catalysts. Is this solely in anticipation of the ensuing NASDAQ up listing? Or, is there more, soon to be revealed, known yet by just a few?
Either way, I'm pleased. I note that the recent low was $2.11, near the end of September. Today's close, at $3.95, is a gain of about 87%.
Let's watch (as we all will) to see how, if, and at what rate this trend continues.
And, what will be the share price trend and daily percent gains after ALPP becomes a NASDAQ stock?
Lastly, what will be the effects of new product development and sales data, in the coming year?
Everything Alpine 4 Holdings looking good. 2022 is going to be very rewarding for those with ALPP positions.
But, will the thunder be Down Under?
Well, Anavex has another one.
MIT Press Publishes Alzheimer’s Research Book
https://mitpress.mit.edu/books/how-not-study-disease
The author, Professor of Neurobiology and an Investigator in the Alzheimer's Disease Research Center at the University of Pittsburgh School of Medicine, gives an inside view of Alzheimer’s research and the continuing search for a “cure.” (No indication that Anavex is mentioned.)
Wha happend?
How come the big share price rise, starting at 2:30pm?
Side effects written, not spoken.
Anavex revenues.
Blarcamesine TV ads.
No problems with blarcamesine information or sales. Easy.
Eventually, Anavex in all EMS vehicles?
Another Anavex CNS indication — stroke.
Interesting paper. Wish I could read the whole thing.
But it’s an Elsevier publication. That publisher charges for access to entire papers, beyond the posted abstract.
https://pubmed.ncbi.nlm.nih.gov/34582837/
First, if sigma-1 receptor activation does alleviate the blood–brain barrier disruption caused by cerebral ischemia strokes, there is a gigantic market for this; and hundreds of thousands to millions of stroke patients would benefit profoundly.
But, because I couldn’t read the actual paper, I could not read the details of how this was determined. What was the specific sigma-1 receptor agonist used in the study? Could it have been as good as blarcamesine or Anavex 3-71? What was the dosing regimen? What were the therapeutic results? How were they assessed?
Once again, yet another CNS disease or condition ameliorated by sigma-1 receptor activation. So far, no other drugs have matched the safety and therapeutic outcomes of blarcamesine or Anavex 3-71.
Let’s now see a clinical trial with our drugs, for ischemic strokes; first, as in this study, in mice. Then, real humans.
A candidate family of blarcamesine rare diseases.
As I’ve contended before, there is a group of closely-related rare diseases for which blarcamesine is very likely to be profoundly therapeutic, even prophylactic.
As a biologist, I’ve studied these closely. I, personally, have one of the diseases.
The family of diseases are those included in HSP, hereditary spastic paraplegia (of which there are a wide diversity of genotypes and phenotypes), and primarily lateral sclerosis (PLS).
In all of these, neurons fail to function properly. Most often, neurons controlling muscles (motor neurons) become hyper-excited, firing often, strongly, or continuously. That causes the spasticity, the continuing contraction in various muscles.
Personally, I have a very mild, late-onset version of HSP—which, in fact, was not hereditary. Many cases of HSP are actually spontaneous, not genetically inherited; merely an incidental mutation. Neither of my parents had HSP, and neither of my children inherited it; thankfully. In my case, the motor neurons controlling the adductor muscles of my legs (and a few other, minor ones, especially in the bladder—now have a suprapubic catheter) are continuously taught. I can walk, with a walker; am able to drive a car very safely and effectively; but couldn’t operate a stick-shift car. Can no longer ascend stairs.
For those with more severe HSP, a rubber bladder is surgically implanted the spinal column. It exudes into the nerves controlling the legs gamma-aminobutyric acid (GABA). This is the chemical missing in the affected motor neurons. GABA is an important (well, crucial) suppressor of nerve over-activity, hyper-excitability. When deficient, nerves fire too easily, causing all sorts of end-of-nerve anomalies.
My case of HSP is not bad enough to prompt the intense surgical procedure of implanting the rubber bladder in my spinal cord, thankfully. My case does not seem to be advancing, thankfully.
Here’s where blarcamesine will come into play with probably all forms of both HSP and PLS. In virtually all cases, neurons are lacking proper, effective concentrations of GABA; hence the over-excitability of the nerves. It was noted in the early findings of blarcamesine against Rett syndrome, in the early safety/tolerability study, that levels of GABA were dramatically increased, normalized by the drug; yielding increased normalization of motor neuron function.
Many years ago, there was a small study of blarcamesine included in the drinking water of lab rats with HSP genes. Like myself, they had reduced control and function of their spastic rear legs. Then, after they drank water with some blarcamesine in it, they rather promptly (in a week or two, as I recall) regained complete motor control of their leg muscles and twirled inside the exercise wheel like normal rats. Blarcamesine (Anavex 2-73) completely obviated the GABA deficiency, allowed normal walking. A cure, dare I say.
(Two years ago, my computer hard drive crashed; I lost the copy of that report; which I believe was in France. I’ve been unable to find it on the internet. If anyone can retrieve it, please post.)
A rare disease? Yes. “The HSP incidence rate in the United States is about 20,000 people.” But for many, very tragic, in the most severe cases:
https://sp-foundation.org/understanding-pls-hsp/hsp.html
When available, I’ll be one of the first to take blarcamesine, off-label, for my HSP. Will be rather expensive, my health insurance won’t pay for it. May have to liquidate a few AVXL shares, then.
Blarcamesine does this.
My Schwab Account Says I Gained
Schwab says my several thousand shares of AVXL ended the day, up 2.61%.