There will be no useful competition.

Will there be “competitors” for Anavex 2-73 (blarcamesine)?

They already exist. There are 29: https://www.drugs.com/condition/alzheimer-s-disease.html

Blarcamesine’s market share wil not be determined by, nor controlled by the number of different competing drugs. Market share will be determined solely by our drug’s ability to prevent or treat Alzheimer’s. Inasmuch as no other drug has blarcamesine’s unique, propitious mechanism of action (MOA), which works “upstream,” at the root cause(s) of Alzheimer’s, by activation of the sigma-1 receptor protein, each and every competing drug will fail to safely and persistently attain favorable therapeutic outcomes. With the competing drugs, symptoms will be incompletely suppressed, the disease will continue to progress at rates greater than with blarcamesine (which will either stop progression, or actually reverse it).

Anyone seen any data on new or prospective drugs that, like blarcamesine, work at the root, exact cause of Alzheimer’s, at the sigma-1 receptor protein, that, like blarcamesine, restore healthful homeostatic processes in the neuron? Nope. They don’t exist. All of the competitors are still working to fix downstream things (such as beta-amyloid or tau pathologies, after they form).

Blarcamesine does not, and once approved, will not have any effective competition. Anavex Life Sciences Corp will own the Alzheimer’s treatment (and prevention) market. Keeping Grandma, with Alzheimer’s, alive for a few more months won’t cut it. She, and her doctor, will demand treatment with blarcamesine.

The market won’t make Anavex 2-73.

No, the reality is this. The “market” simply has nothing to say or contribute to Anavex 2-73 (blarcamesine) ever being sold or used for disease therapies. That’s the function of the Food and Drug Administration (FDA). They, solely (in the US, at least), decide if blarcamesine “works;” after, of course, considering clinical results data. And those won’t be available until later.

Gonna have to wait. Pretty tough to do, it appears.

Shape ain’t right for toxicity.

Boi, thanks. Perfectly stated.

That’s it. Blarcamesine simply doesn’t stick or bind to anything else in the cell, other than the sigma-1 receptor protein, where it activates a diversity of propitious “downstream” biochemical outcomes; therefore can’t pathogenically disrupt anything. Toxicologically, it’s inert. Pretty nifty for a drug working in the nervous system.

And, you are right about Anavex 3-71. It will prove even less toxic, and far more potent, acting in microgram, not milligram dosages.

Two perspectives: Before or after an FDA decision.

Well, of course, for me it is.

But for various and many parties, it is not. It is for them the contrived truth. For them, until the U.S. Food and Drug Administration formally approves the sale and therapeutic use of a new drug, especially one like blarcamesine, which Is novel and unique in its mechanisms of action (MOAs), the new drug is held to be “unproven,” “of unknown safety,” etc. Simply, an abundance of solid therapeutic evidence in both murines and humans is summarily discounted. For drugs like blarcamesine, the only people authorized and competent to know and pass on the factual realities are the people at the FDA that approve new drugs.

Of course, from a distance one can discern how that can actually work. The FDA approved Biogen’s Aduhelm as a new, innovative, effective (?) treatment for Alzheimer’s.

For those considering the value, present and future, of an AVXL position, it works out in two ways. For those of us who know the profound evidence of both safety and efficacy, from the many pre-clinical murine studies, followed up successfully with early-phase human clinical studies, we are confident that when any of the three existing clinical trials of blarcamesine conclude (for a) Rett syndrome, b) Parkinson’s disease dementia, or c) Alzheimer’s disease), there will be an abundance of favorable data to assure FDA approval.

Others, however, are reluctant to place any confidence in the existing pre-clinical data. Blarcamesine is unlike any other drug; it simply may not work in real humans with real CNS diseases. Too risky to make an early bet, by buying some AVXLs. Those diligent souls, bless their hearts (well, checking accounts) are going to wait until the FDA decides on the matter.

Two differing biotech investment strategies.

Of course...

...blarcamesine's efficacies are now explained. They come from the placebo effect. Should'a known.

Until the FDA pronounces blarcamesine's reality, good or bad, it's all bad or at the most, placebo of some variant.

No, it’s the stock message board effect.

Well, the vast majority of people taking blarcamesine who are allowed to choose whether or not to continue with it after the trial they are in elect to continue is 95%. Obviously, that’s a rather impressive majority. How can that be accounted for?

First, understand “the placebo effect.” In the simplest, people taking what they think is a “good drug” presume that it will necessarily work. It’s being administered by real medical people, in a real medical environment, for a real medical purpose, to prevent or treat a real disease that they have. With all of this in play, patients taking what is, in fact, a colored starch pill (of no medical function whatsoever) will joyfully report that “it works.” Mind over matter.

Very clearly (to many, anyway), with this 95% preference to continue to take what is already known by medical experts as a useless, non-functioning drug (blarcamesine), a new variant of the placebo effect is now at play. Let me describe (and name) it.

The people in the clinical trial, now in the 21st-century, have access to all the world’s knowledge, right on their cell phones or computers. All of the people (well, at least 95%) in the trial got on the Internet and looked up “blarcamesine.” Lo and behold, they found a lot of “info” on an Anavex Life Sciences Corp stock investment message board, where they found a bunch of people telling all of the good benefits of the drug they were taking. Lots of articulate people telling lots of detailed benefits of the drug. Hence, at the end of the trial, 95% elected to continue with the drug, even though the trial came to an end.

Of course, they are all wrong. The evidence of blarcamesine’s safety and efficacy is woefully incomplete. At least three on-going clinical trials first need to be completed, then analyzed, then pondered by the FDA, awaiting that agency’s approval of the drug sometime in the distant future. Until the FDA approves the drug, it is categorically and unconditionally unsafe and ineffective. Period.

So, in this case we have a new placebo effect variant: the stock message board effect.

Henceforth this will have to be taken into account during drug clinical trials. Participants must be kept from consulting the Internet and web-based information sources (such as stock message boards) where clinical trial participants can mistakenly “learn” bad and wrong things about the drugs they are being tested with. As in this case, they could continue to take a useless drug long after the trial ends, in the “open label extension,” OLE. For drugs such as blarcamesine, that’s just so dangerous; allowing patients to be mentally deceived.

So, there. We’ve nailed it. So very clearly the 95% electing to continue with blarcamesine, after the clinical trial has formally ended, have done so because of the “stock message board effect,” not at all because they actually benefitted, had improved health. That can’t be. The drug isn’t yet approved by the FDA.

It’s not just my defense.

Thanks.

My arguments are pretty standard within the academic community. Every scientific study, and its consequent paper, has to stand up to intense questioning by fellow scholars. Anyone who’s defended a master’s or doctoral thesis knows the game. The candidate does a study, then very carefully tells all that was discovered. Finally, academic advisors, in a formal event, try to disqualify both the paper and the candidate, by asking every sort of question about study and the paper. “Mr. Jones, how could you claim that ... is valid? Aren’t you familiar with Dr. Dorgalson’s work showing exactly opposite of what you claim?”

Contesting verbal, argumentative pokes and jabs about everything in the paper. Get something wrong, or fail to verbally defend it, and start all over.

That’s how science works. Don’t accept anything without actual experimental data that substantiate the validity of new ideas.

My point is this. Yes, I’m a retired high school advanced placement biology teacher, now conducting high-level, world-class ecological studies at a university, which will solve a major ecological problem. At every step, I’ve had to answer the “How can it be....?” questions. That’s what good scientists do. Try to find why some new concept or protocol is invalid. No one is finding any of that with blarcamesine. There are lots of academic and medical science professionals scrutinizing the expanding Anavex story. They, too, can’t find anything wrong with Anavex science. Their silence on the matter is definitive.

The lack of evidence of unsafety or inefficacy.

This, exactly, is what I spent many hours looking for, when I first heard of Anavex and Anavex 2-73. Too good to be true. There had to be unrevealed or poorly-described negative factors with the drug. Yes, it works in nerves and the CNS, so there almost surely must be side effects and/or efficacy complications—the case with virtually all CNS drugs (even aspirin).

So, I searched PubMed and all the other academic info sources to learn everything I could about the drug. There were lots of papers and data. But missing in every single one of them was any discovery or mention of complicating side effects. The drug didn’t (and doesn’t) have any. For a powerful CNS drug, “too good to be true.”

But in all of the papers were the opposite: presentation of data showing degrees of efficacy. The drug works therapeutically.

But, please note. It would be one thing for a proponent of Anavex (myself) to proclaim both safety and efficacy; but quite another for an Anavex naysayer to lay out the drug’s safety and efficacy problems. Seen any of those recently? Of course not. They don’t exist.

Dare I say, there is now universal agreement on blarcamesine’s safety. No one, proponent or basher, has posted any side effects problems with the drug for some time. None can be found, by anyone, pro or con. Then, when the Rett study data are released, no one will be able to claim that blarcamesine can’t fix things in diseased nerves.

My proclamations of blarcamesine safety and efficacy are valid. But the even greater matter is the inability of Anavex opponents to lay out and describe information that negates those contentions. If there were any safety problems, we’d have heard about them. The silence on that matter is definitive, altogether. Next, and finally, will be the Rett study data, conclusively and universally proving therapeutic efficacy.

For traditional CNS drug therapies, game over.

Again, the profound blarcamesine safety factor.

The blarcamesine “safety factor” should not be neglected; it’s major.

Think not? Look up the drug info on any of the prescription drugs acting in the central nervous system, and compare their side effects and dosage warnings (to physicians), compared to the infrequent and very mild side effects of blarcamesine: a few headaches or an upset stomach, in most cases spontaneously resolving after a short period. No disruption of genes, hormones, or other biochemical processes, etc.

When very reactive chemicals enter the brain or nerves (after passing through the blood-brain barrier; often requiring large doses to do this, to get some of the drug into the target tissues) all sorts of biochemical or genetic disruptions are induced. For CNS diseases, for the few drugs currently available, prescribing physicians must always carefully balance dosages against the adverse events (side effects) the drugs are noted for. The drug may reduce certain CNS disease symptoms, but at the same time induce all sorts side effects.

With blarcamesine, the dosage-against-side effects calculation will be simple. Simply not much of a factor.

And, yes, in every single murine and human test of blarcamesine, side effects have been either minimal and mild, or simply absent.

All of that was one of the first things I wanted to learn about, when I learned of Anavex 2-73 (blarcamesine). What side effects appear at various dosages? I was astonished to find virtually none that paralleled those of existing CNS drugs. Simply, blarcamesine does not disrupt other, non-target molecules or reaction pathways. It sticks (literally) to the molecules that can benefit; not to others.

The turning point to come.

Oh, the “financial community” is not too smart; unable to comprehend either Anavex science itself, or how it will play out therapeutically?

Let’s watch. When the Rett clinical trial results are released, they will show, conclusively, that blarcamesine is able to safely modulate, promote normalized neuron functions, by means or mechanisms belonging to no other company.

The “financial community” is not dumb. With the Rett results, they will very quickly learn the essential biology of the Anavex molecule and see its implications. It will be both a financial and medical technology turning point.

Like the trends.

Well, I purchased a few hundred AVXLs this morning, at $18.52. It’s my first purchase in several years; had a few discretionary dollars to put to work (well, bet on increasing value of AVXL). At the end of the trading day, very satisfied.

I then listened to the segments of the online conference call that weren’t silent. Everything I heard confirmed my expectations; all positive. When the transcript gets posted, I’ll scrutinize everything and re-evaluate. But with Rett results out in the second half of the year, Christmas may be rather joyous. Those data points will substantiate in humans the blarcamesine mechanism of action (MOA), activating the sigma-1 receptor protein, with all of the consequent good things in neurons. The murine (lab rodent) data are revolutionary, but discounted because mice aren’t men (or girls with Rett syndrome).

When the Rett and Alzheimer’s trials data are released, late this year and into next, postings on the Anavex Ihub board (this one) will be different. Gonna be hard to tell how bad Missling is, and how blarcamesine is a failure.

From the start of my interest (and equity investment) in Anavex Life Sciences Corp a number of years ago I’ve always looked to 2023 to be the year of the company’s operating success. It will then be selling blarcamesine across much of the globe, for a diversity of indications. Right now, my composite AVXL cost basis price is $2.33. In a few years, should I be liquidating any of my position (have no intention of doing so), I’d have some substantial capital gains taxes. Instead, I intend to hold my position, reap eventual dividends, but pass the position on to my estate beneficiaries, my wife and children.

Everything trending as anticipated; slowly but deliberately.

Blarcamesine can replace Aricept, immediately.

As I recall, there may be some evidence that Aricept can also bind to, become a sigma-1 receptor protein ligand. If that is so, it is inconsequential, inasmuch as there is no evidence that Aricept can activate the sigma-1 protein to the effective degree that blarcamesine does.

Within the cell there are thousands of different proteins and other non-protein molecules; all in the realm of organic chemistry, wherein molecules are mutually “sticky,” they bump into each other and often “stick,” at least for an instant. When that happens, the new molecular complex of both of the stuck-together molecules takes on entirely new chemical traits and actions. Aricept may well bind to the sigma-1 receptor, but very clearly it is unable to facilitate that protein’s seminal modulation of homeostatic processes.

The prime mechanism of action (MOA) of Aricept is as an acetylcholinesterase inhibitor. Simply, it suppresses the acetylcholinesterase enzyme. In so doing, it inhibits acetylcholinesterase from breaking down the neurotransmitter acetylcholine; proper acetylcholine concentrations are maintained; neurons are then able to properly “fire,” transmit messages. Those, of course, are essential in thinking, memory, etc.

Then, what might be the time required for blarcamesine to work in patients already being treated with Aricept? I see no reason this would not be immediate. After Aricept is stopped, it will be cleared quickly; it does not bind strongly (if much at all) to the sigma-1 receptor protein. Blarcamesine strongly and quickly binds to it, even at very low concentrations.

No competition; nothing else can work.

This greatly separates blarcamesine from the few other drugs approved for and used to treat both Alzheimer’s and Parkinson’s disease. There are a few; for Alzheimer’s, Aricept is the most prominent. But it merely slows, for a time, the lethal progression of the disease. Without exception, those with Alzheimer’s, taking Aricept will eventually experience the fateful, even lethal outcomes of the disease. For a time, at the start of therapy, their progression will be only moderated or delayed.

This is crucial. Aricept does not, cannot terminate the root causes of Alzheimer’s. It merely smothers, for a time, the bad symptoms. The underlying pathogenic processes continue, sooner or later overwhelming the ability of Aricept to douse the increasingly bad symptoms.

This is where blarcamesine is utterly different. By its favorable activation of the sigma-1 receptor protein, it causes it to resume it’s proper functions of modulating homeostatic processes, including those that facilitate proper folding of proteins (enzymes), which then go on to healthfully modulate the chemical reactions within neurons.

At the sigma-1 receptor protein, blarcamesine works “upstream” in the flow of chemical reactions and processes that healthfully maintain cell biology. Blarcamesine works at the “headwaters” of the many reaction pathways, causing the “downstream” processes to work as they should, as directed by the genome.

And this, of course, accounts for blarcamesine’s unique ability to reverse the progression of Alzheimer’s (and other CNS diseases). Without effective, restorative activation of the sigma-1 receptor protein, the underlying pathogenic processes of Alzheimer’s and other CNS diseases will be unabated.

And, of course, this same mechanism, blarcamesine activation of the sigma-1 receptor, will prevent the onset of Alzheimer’s. Blarcamesine will not only effectively treat the disease, restoring to some degree (great or small) cognition, but will prevent its onset; the great prophylaxis factor.

The Ponce de León Effect.

Boi, thank you. This is profound; and very plausible.

Could it be that a number of CNS (and other diseases) are actually closely related; have the same general root cause, although with diverse symptoms?

Could that root cause be sigma-1 receptor protein dysfunction, which under varying genetic or age-related conditions result in various CNS diseases?

It’s not insignificant, nor merely chance, that Parkinson’s and Alzheimer’s, except in rare cases, occur with age. Not many 20-year olds suffer from any of the symptoms of either disease. There is a profound geriatric factor at play.

What might that be? With various disease-specific outcomes might it be, simply, reduced production of the sigma-1 receptor protein with age? In some cases or conditions the sigma-1 receptor deficit results in Parkinson’s; in others, Alzheimer’s, etc.? Or, simply, with age, poor activation of the protein, favorably accomplished with blarcamesine?

Again, I’m betting that Anavex has internal studies showing this; a general anti-aging function of blarcamesine, as it restores sigma-1 processes, and/or induces greater production of that protein. The first testing of this would be in the roundworm Caenorhabditis elegans, a common lab animal used for aging studies. It can be easily cultured (grown), after which all sorts of factors can be used to induce aging. During that, the aging process, even at the cellular level, can be intently studied; all in just a few short weeks.

Might I suggest (ever so prematurely) that when this anti-aging function of blarcamesine is adequately demonstrated, that it be called the Ponce de León Effect, which happens not in Florida (which the Spanish explorer putatively but not in fact is credited with promoting in that peninsula) but in actual body cells.

There is the real prospect that, in time, Anavex molecules will be used prophylactically, to prevent the onset of a number of diverse geriatric diseases and conditions. The mechanisms of action for this are now in view; awaiting confirmation in humans.

But, what’s at stake?

Yes, we must.

Consider, who has the most to lose if Anavex goes bust on blarcamesine? Personally, I’ve got a very moderate fraction of my disposable, discretionary investment dollars tied up in AVXL. I sure don’t want to lose them. But if Missling can’t get blarcamesine approved anywhere for therapeutic uses and sales, I’ve lost my dollars.

Should that happen (it won’t), how many dollars will Missling himself have lost?

In stock investing, “insider buying” of an equity, where company insiders buy shares of their company, is always a very positive message. If insiders buy, they do this with information that is not so available to “outsiders.”

Missling, in the past, has done some inside buying. Positive enough. But presently, he doesn’t have to buy more AVXLs. He’s got a pile of them already, and apparently, options to buy more at the right time (at the right price). Simply, he’s already “fully committed” to making Anavex a success. If he succeeds, if blarcamesine gets approved, he will be exceedingly wealthy. If he fails, well....

Missling has my interests in mind when he makes executive decisions. In fact, we share those interests—make blarcamesine a success. Because of what’s at stake for him, he will make no cavalier decisions or fail to act. For him, everything’s at stake.

And, the Anavex science supports all that he’s aiming at. Anavex and blarcamesine are not blind shots in the dark. No shots at all. Blarcamesine will be taken by swallowing a pill, with a glass of water. Thereafter, it will work its wonders.

Thank you, Dr. Missling.

Well, blarcamesine is bad, regardless.

Of course not. Watch. When the FDA actually approves blarcamesine for Rett there will be posts that wil tell us why that approval will be proven invalid; that blarcamesine is actually poisonous and utterly ineffective. There are people who really know how bad blarcamesine really is. As they have already, they will let us know. They know more than the FDA.

Extremely powerful, at minute dosages.

Thank you for the invitation, but it would be best for someone more competent in the specifics of reaction dynamics to fully elucidate the data presented for the three Anavex molecules.

But it is clear, at the sigma-1 receptor, both Anavex 3-71 and Anavex 1-41 work far more strongly, in far lower concentrations than blarcamesine (Anavex 2-73). The effective, reactive concentrations of the first two are measured in nanomoles (nM), compared to the micromoles (µM) of blarcamesine (Anavex 2-73).

A micromole is one-millionth of a mole. A mole is a standardized unit in chemistry, having 6.02214076×10 to the 23rd) particles, in this case, molecules.

A nanomole is one-billionth of a mole, one one-thousandth the size of a micromole.

To be effective, blarcamesine needs concentrations a thousand times greater than either of the other two Anavex drugs. Is that, then, a problem?

Nope. As both murine and human therapeutic data have shown, blarcamesine works wonderfully, with great safety and efficacy at its much higher concentrations. “Higher” in regard only to the other two Anavex drugs; not in comparison to the concentrations of the other Alzheimer’s drug, Aricept (donepezil). That drug is prescribed in milligram doses much larger than blarcamesine.

What might be the takeaway?

Simply, Anavex 3-71 works in extremely low concentrations. Therefore, it is less likely to cause side effects. And blarcamesine, at it's far larger dosages, has few side effects; none that disqualify it.

For Anavex, across the board, safety and efficacy. (In the central nervous system, even.)

They know, as do we.

Surely, at least the first portion of this statement is true. They can read the same studies on the Anavex sigma-1 receptor agonists that we (and Dr. Hagerman) have. They are online, in the public domain; not hidden at all. No beans about it.

More important is how anyone will respond to learning of Anavex science. Most, not well trained in cytology or molecular biology, will summarily dismiss the data. Just too good to be true, effectively and safely dealing with a variety of CNS diseases that conventional drugs cannot. “Sure, a simple little molecule diffuses across the blood-brain barrier, gets into neurons, attaches to a particular resident protein, whereafter all sorts of healthful and restorative processes take place. Get real.”

Well, because they can see the biology, Big Pharma people have gotten real. They see the safety and validity of the mechanisms of action (MOAs) of blarcamesine just as well as those of us here (and Dr. Hageman). There’s nothing mystical or magical at play; just unique, proprietary biochemistry.

Which, then, raises the question of the second half of the statement. Can or will Big Pharma somehow thwart the eventual approval of blarcamesine, by either the US Food and Drug Administration (FDA), or, down under, the Australian Therapeutic Goods Administration (TGA)? Specifically, how might that be accomplished, after profoundly safe and effective human trials data are produced? When the girls in the Rett trial demonstrate therapeutic results of statistically-validated safety and efficacy, how will Big Pharma (or anyone else) keep the drug from being approved (in at least two countries)?

It will be even tougher after the Parkinson’s disease dementia trial data are released to the public. Then, even stronger and utterly conclusive will be the Alzheimer’s data; again in at least two different countries.

If Aduhelm can get approved with such meager outcomes data, with very severe and frequent adverse events, after good trial results appear there doesn’t seem to be anything that could keep blarcamesine off pharmacy shelves. But a matter of time; for the three blarcamesine clinical trials to conclude.

Our postings; and Dr. Hagerman’s.

— Good listing of the many contributors providing positive info supporting the future of Anavex Life Sciences Corp.

I’ve posted a few of those myself. Understandably, outsiders, and those who know little about Anavex science, will be skeptics; discounting the things we post. Too good to be true. Our posts are in one category; but those telling of Dr. Hagerman’s statements about blarcamesine are on a different, much higher plane.

Dr. Hagerman is a world-class expert in the central nervous system diseases she treats and conducts clinical trials on. The good woman hasn’t seen blarcamesine from afar. She’s watched patients in her clinical trials take the drug, and has subsequently studied, first hand, over time, what it does. Her statements are as positive and supportive of blarcamesine as any that the rest of us have put up. But, they are first-hand experiences with the drug, in real people, severely debilitated by CNS diseases. No one could be more qualified to state, accurately, both the safety and the multiple efficacies of blarcamesine.

Personally, I was delighted when she stated that she very much wishes to take the drug herself, for its various prophylactic benefits; warding off the onset of various geriatric CNS conditions. Some time ago, I was one of the first to claim that this should be considered, that the taking of blarcamesine would some day be common, perhaps universal in late middle age.

But although I’m a research biologist (in an entirely unrelated field), I don’t even know what a blarcamesine pill looks like. I stated my conjectures based upon the detailed biology of blarcamesine; mostly in murines (lab rodents). Dr. Hagerman knows all of that, too. She’s read the same papers I have on blarcamesine biology. She came to the same conclusions I did. Not much attention connected to my conjectures; understood. But the statements of Dr. Hagerman have weight; to come finally into play when the Rett and Parkinson’s disease dementia clinical trials results appear. They will confirm everything all of us here, and Dr. Hagerman, have been proclaiming.

Let the trials conclude!

No MOA competition.

Were that to happen, it would complicate matters.

Won’t happen, however. No one else has a new-drug mechanism of action (MOA) that effectively works as a sigma-1 receptor activator, facilitating any of the many positive downstream outcomes caused by blarcamesine. The only competition is Anavex’s own other drug candidate, Anavex 3-71, which shares blarcamesine’s MOA, but works at concentrations threes orders of magnitude less than blarcamesine.

“Yea, but what if somebody else comes up with a new drug candidate that actually does work at the sigma-1 receptor protein?”

Ok, any chance they can get their drug approved any faster than Anavex? It would take five to ten years. By then, blarcamesine will have been on the market for many years, effectively treating and preventing various CNS (central nervous system) diseases. Anavex, with either (first) blarcamesine, or (perhaps later) with Anavex 3-71, will be the SOC (standard of care). Any new drug would have to at least match Anavex’s efficacies, and at the same time have equal safety.

Stuck in the past.

Read a new article in Science today, the weekly journal of the American Association for the Advancement of Science (AAAS): Treatments for Alzheimer’s disease emerge.

And, of course, the words “Anavex,” “blarcamesine,” or “sigma-1 receptor” did not appear. Focus was solely on beta-amyloids and tau tangles.

Some verbiage on immunological approaches (Biogen’s Aduhelm, etc.).

Of course, the author is an “expert,” at Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA.

Cherries and watermelons.

The MOAs (mechanisms of action; how they work biochemically) are entirely different, as comparing cherries to watermelons. Blarcamesine, from the start or top of biochemical problems in the neuron, fixes them. Everyone else tries to fix things from the bottom, cleaning up or removing wastes after they have been formed. At the sigma-1 receptor protein, blarcamesine stops the waste (pathology) problems at their start.

Nothing changes until sales approval happens.

No, how the Alzheimer’s prophylaxis trial results will be “understood” is very clear. Yes, Alzheimer’s will be significantly prevented or its onset delayed. Alone, that will be game-changing.

At the same time (during the trial) it will be noted, perhaps only “anecdotally,” that trial participants had other good health benefits. Problem is, those won’t be sufficiently detected or assessed; the trial will focus solely on the appearance of Alzheimer’s. All the other good stuff will be anecdotal, simply reported verbally by participants. “Yep, the Alzheimer’s my mother got, for which I, too, was destined, simply didn’t appear. That’s great. But, not only that, I slept better than any time in my life. I woke up refreshed and could work harder the whole day through. And, I never got a cold or the flue. My blood pressure even went down.”

But nothing beyond the appearance or occurrence of Alzheimer’s will be accepted as “evidence.”

From the start of the Anavex sigma-1 receptor agonist story, one overriding, controlling perspective has been imposed; just as with today’s sell off of AVXLs after the news of the Alzheimer’s prophylaxis trial being planned. It’s this. Everything about the science of the Anavex molecules pushes hard against what is known and believed. It simply can’t be true. If it is (if blarcamesine actually works in humans as it does in lab rodents), the majority of professionals in both medicine and biotech financial advisory positions will be shown to be utterly and tragically wrong. They are the real experts. They have MD and MBA degrees. They KNOW THEIR STUFF, and the stuff of Anavex just can’t be true.

Treating Alzheimer’s with a daily pill taken with a glass of water? Get real. Neurons can’t be fixed that way. Then, even weirder is the notion that that that pill would actually prevent the onset of Alzheimer’s. Just can’t be so.

And that will be the case until real people actually take blarcamesine for a time and hard data show the real benefits of blarcamesine. That probably won’t be until some time in 2023. Then, silence. The Anavex naysayers, in both the medical and investment communities, won’t be heard from again.

Medical professionals since the middle ages have almost universally rejected new information that negated what they learned and believed. It took about three generations (75 yrs?) for the crazy “germ theory” to be finally accepted and applied in both medicine and public health. The experts knew better.

Invisible “germs” causing diseases was a hard thing to accept. Didn’t fit in any way with what was clearly known and believed. With Anavex’s sigma-1 receptor activators, it’s the same situation. Back in med school nobody ever talked about sigma-1 receptor agonists, or any involved pathologies. For Alzheimer’s, “everyone knows” that it’s caused by accumulations of beta-amyloids and tau tangles.

Of course, the only “experts” that count are those in the drug approval positions at the FDA (or the Australian Therapeutic Goods Administration). When, in their ultimate wisdom they approve the sale and therapeutic use of blarcamesine, some general reality of blarcamesine efficacy will begin to prevail. But not until then. Until sales approval of blarcamesine, blarcamesine in particular, and Anavex in general, will continue to be nay-sayed. The experts “know.”

Results of the Alzheimer’s prophylaxis trial.

Consider, however, what else such a trial is likely to reveal. Not only will the frequency and severity of Alzheimer’s be dramatically reduced, but the other health benefits of blarcamesine will reveal themselves; better generalized health. Specifically, reduction of the aging process, with a multitude of good outcomes.

As previously conjectured (by Drs. Missling and Hagerman and me), blarcamesine will be prescribed, to be taken daily, by everyone starting in the mid-40s.

No effects whatsoever.

No, unless the SAVA drug has spooky actions on other drugs (abilities to change their biochemical effects in distant individuals taking the Anavex drug), the SAVA drug’s clinical outcomes are utterly unconnected to, unaffected by those of blarcamesine.

It seems that many believe that for whatever reason there can be but one drug to treat Alzheimer’s, and that most likely will be the SAVA drug. Is that magical thinking?

The reality will be this. The SAVA drug may well provide a modicum of good benefits for patients with Alzheimer’s. The Anavex drug, blarcamesine, will be far better; better clinical outcomes, longer lasting, and safer. Both patients and physicians will prefer blarcamesine.

End of story.

Important correction.

I just got a private message from a frequent, very helpful board member. I appreciate his message to me. VERY important (and accurate).

He notes that I made this claim: "As noted previously, blarcamesine, against Alzheimer’s, is effective in about 80% of those with the disease."

But here’s the correction:

Yes! Thank you; a point I failed to make. For a fraction, about 20% of those with Alzheimer’s, blarcamesine does not work as well. It will take either/or longer for it to take effect, or larger doses.

I’m betting that for people with unfavorable blarcamesine genetics, dosages will have to be carefully titrated (slow, small incremental dosage increases) to the level of efficacy. This probably will take time, many weeks or months. But, in the end, symptomatic relief, at least to some degree, will be attained. Getting there will take greater time and effort. Success, nonetheless.

Then, of course, next will be the question of Anavex 3-71. Will it work for everyone, or will it, too, need titrated dosage increases for some?

Again, for the poster who sent me the private message, thanks. Blarcamesine is better than I portrayed it; will help almost everyone with Alzheimer’s; but may take longer for some, with carefully titrated dose increases. Far better than anything available now for Alzheimer’s.

Product advancement.

Well, yes, if Anavex 3-71, at its much lower dosages and greater therapeutic successes thoroughly outperforms Anavex 2-73 (blarcamesine), would that be good, or bad, for the company?

There will be no conflict. Should Anavex 3-71 prove to be better (as I’m certain it will), Anavex will simply market it as what it is, a new, even better sigma-1 receptor activator. It’s what every good business does. Create new, even better products, to replace older, less favorable ones.

In say, five years or so, after blarcamesine is the standard of care (SOC) for a number of big diseases, can you imagine the Anavex advertising campaign: “First, changing everything, it was blarcamesine. Now, even better, it’s (new product name)! Ask your doctor about (new product name)!

Contract likely to be signed.

A “term sheet” is a document arranged and exchanged by parties anticipating a contract or financial arrangement between them. It is mutually negotiated by both parties, with the aim of making a final legal document that can be executed; agreed to.

A term sheet for the “Durango location” would indicate that a final, legal contract or agreement is being mutually arranged; likely to happen.

The potential of Anavex 3-71

First, for myself and many others, I want to commend georgejjl for his always-informative and detailed posts; information buried in the dozens of papers and studies on Anavex molecules. George, you so helpfully pull out and post the most information needed to understand the deep science of Anavex. Your postings continue to highlight and validate the science that will make Anavex Life Sciences Corp a major pharmaceutical in a few years. Our thanks.

For example, your new post included this:

Understandably, the prime focus by Anavex has been with blarcamesine, the company’s lead new drug. Doubtless, it will be big, for Rett syndrome, Parkinson’s disease dementia, and for Alzheimer’s—as the trials for those diseases will reveal. But, as the above quote notes, Anavex 3-71 will likely be even stronger and safer. Patients will be getting doses measured in micrograms, not the milligrams of blarcamesine. A microgram is one one-thousandth of a milligram. Dosages of Anavex 3-71 will be generally three orders of magnitude lower than blarcamesine, with safety up to more than 50,000 times the minimally-active dose.

As noted previously, blarcamesine, against Alzheimer’s, is effective in about 80% of those with the disease. They have genetics that favor blarcamesine function. But, there is the distinct possibility that Anavex 3-71 could make up the difference, working well in those with unfavorable blarcamesine genetics. Or (very likely), Anavex 3-71 may replace blarcamesine altogether. Future trials will determine this. The molecule’s safety and tiny effective doses strongly suggest it.

Lastly, of course, will be prophylactic use of either drug; to prevent the onset of a diversity of age-related diseases and conditions. Anavex 3-71 will be a strong candidate for this. Trials will test and prove....

But a love of what sort?

Well, that would be nice. But affections from market movers who claim Wall Street as their venue are of significance only before the big, final clinical results are released from any one of the three on-going blarcamesine clinical trials. Instead of love, those data will move the AVXL share price.

Most likely, the Rett results will appear first, with data points that validate the unique mechanism of action (MOA) of blarcamesine, operating in nerve cells; against a heretofore un-treatable central nervous system disease.

But, of course, the Anavex naysayers of every stripe will note (well TELL us) that Rett syndrome is but a rare genetic disease of little girls. Nice, but of no real investment significance (it will be claimed).

Then, it will be the Parkinson’s disease dementia study. Profound results, there, too. But, of course, the very first thing that we will be warned about is that “It was NOT a study of real Parkinson’s disease, just a less common, less significant sub-type. Not really important.”

Then, finally, it will be the big Alzheimer’s results. Like the others, they will be profound; game-changing for Alzheimer’s sufferers. The Anavex naysayers, finally, will be silenced. Nothing they can say. FDA or TGA (Australian Therapeutic Goods Administration) approval of the drug will quickly follow. The AVXL share price will continue the ascent begun with the Rett results.

Long-suffering patience is required—for both AVXL shareholders and those with the CNS diseases Anavex is targeting (and will treat).

Pretty deep, but phenomenally significant.

insert-text-here

Well, thanks. Once again I turned to the paper, read it closely, with the goal of explaining what was investigated, and what was found. But, as anyone will quickly perceive when trying to read it, the article is extremely info-dense, with information not familiar to those not so competent in cellular biology, etc.

I first tried to condense and summarize the article for readers here. But after about the second page, of multiple big paragraphs with lots of terms that had to be explained, I gave up. Few would want to read much past my third paragraph. Scientifically arcane stuff; very hard to explain in a few paragraphs. So, let me tell what I found; what the paper discovered.

The study analyzed the “exome,” the genetic nucleotide sequences of participants, looking for portions of DNA (genes) that would correlate with therapeutic responses. Pretty advanced stuff, yielding very precise data; answering the question, “What genetics will allow blarcamesine to work, provide therapeutic results?”

I found this statement to be (for me at least) the most significant: “...the higher blarcamesine (ANAVEX2-73) mean concentration arm had improved therapeutic responses of 78% and 88% in adjusted MMSE and adjusted ADCS-ADL, respectively, relative to the low/medium arm at 148 weeks (P-values < .0008 and <.0001, respectively). In addition to time, APOE e4 status (P < .0001), and blarcamesine (ANAVEX2-73) mean concentration were significant predictors.”

Simply, for 78 to 88 percent of the humans being tested blarcamesine provided extremely significant therapeutic improvements.

First were the Mini-Mental State Examination (MMSE) numbers. The MMSE test runs like this: “Ask for the date. Then specifically ask for parts omitted (e.g., "Can you also tell me what season it is?"). One point for each correct answer. Ask in turn, "Can you tell me the name of this hospital (town, county, etc.)?" One point for each correct answer.” Simply, it’s a test of normal thinking, cognition skills—exactly what’s missing in those with Alzheimer’s.

The ADCS-ADL testing assesses the competence of patients with Alzheimer's Disease in basic and instrumental activities of daily living. The other deficiency factor in people suffering from Alzheimer’s.

Then, of course, were the “p-values.” Those indicate the chances that favorable results might have been by chance, not exactly by the drug being tested. P-values determine “statistical significance.” To be statistically valid (“significant”) there must be no chance greater than one in twenty that the results were random, not “significant” or actually caused by what it being tested. P values are in the range from 1.0 to 0.0, expressed in hundredths. A p-value of 0.05, the stat-sig cutoff (higher values indicate randomness, not direct effect) is a value of one-in-twenty.

Well, look at the study’s p-values: < .0008 and <.0001. Simply, blarcamesine works, profoundly in the majority of those with Alzheimer’s. But, as the genomic analyses show, not so well in 12 to 23% of those with the disease. They have genetic variants with reduced responses to blarcamesine.

What does all of this mean? Again, blarcamesine really does provide profound therapeutic outcomes for the majority of those with Alzheimer’s. Cognition was actually improved, not just maintained.

But, for a few, at the concentrations used in the study, blarcamesine had reduced or minimal therapeutic outcomes.

There is no doubt in my mind that when the final Alzheimer’s/blarcamesine study data appear, they will simply confirm these earlier data. With that, blarcamesine will get regulatory approval for sales and therapeutic use. In this study, the data are clear as day. Significantly improved scores of cognition and daily living, all with statistical significances entirely obviating any chance or otherwise anomalous causes. For most, blarcamesine WORKS for Alzheimer’s.

But what about those with unfavorable genetics, the 12 to 22 percent of study participants? For them, two additional studies will be needed. I perceive a really good chance that blarcamesine might be able to prevent the progression of Alzheimer’s in those people, if administered prophylactically, before and just at the appearance of symptoms; before the disease has set in and caused it’s cellular anomalies; or, those people may need much larger doses.

(Or, later, they will need Anavex 3-71, which very likely has differing underlying genetics.)

Good question.

Perhaps; but could be known only with expensive, lengthy clinical tests... which I doubt will be needed or in any way suggested, once blarcamesine demonstrates, by itself, thorough and safe suppression of Alzheimer’s symptoms.

Given its safety and efficacies, after the on-going trials are complete, blarcamesine is going to be unbeatable (except perhaps later by Anavex 3-71).

Very different.

Here’s what Cassava Sciences claims about it’s new drug simufilam: “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.”

So, it restores the shape and function of filamin A, “a scaffolding protein, in the brain.” Well and good.

Next must be clinical trial results confirming both safety and efficacy. In the clinical trials required by the FDA for sales and use approval, will the drug be successful in both safety and efficacy? Yet to be determined or demonstrated.

I haven’t deigned to search out and scrutinize the pre-clinical studies on simufilam, so I can lend no understanding of how those data and outcomes might project the regulatory future of the drug. If it works, well and good.

But I don’t see this as a potentially negating competitor to either blarcamesine (Anavex 2-73) or Anavex 3-71. First, Cassava’s simufilam, as best as I can determine, is aimed solely at Alzheimer’s. The Anavex drugs are targeted, presently (more to come), at three CNS diseases, Rett syndrome, Parkinson’s disease dementia, and Alzheimer’s. Far broader applications, with far broader mechanisms of action. More "upstream," favorably fixing a diversity of "downstream" biochemical anomalies.

And, very different mechanisms of action. Cassava’s simufilam favorably reconfigures just one particular protein, filamin A, which may indeed help suppress Alzheimer’s. But for other CNS diseases, doubtful.

In summary, Cassava and Anavex, while both targeting Alzheimer’s, are on very differing “pathways.” I’ll go with Anavex. Their drug, blarcamesine, causes the cell (neurons) to properly configure, fold, a diversity of “downstream-acting” proteins (primarily, enzymes) which then healthfully normalize a diversity of cellular functions; not the least of which is autophagy, the ability of the cell to consume and reprocess chemical wastes (such as the protein wastes, beta-amyloid and tau clusters) that apparently cause or contribute to Alzheimer’s.

Are the institutional owners of AVXLs ignorant?

If Anavex has insufficient rights to the commercial use of their sigma-1 receptor activators (blarcamesine, etc.) and this is a legitimate risk, are the institutional owners of millions of shares of AVXL ignorant of such? Why haven’t they perceived these putative risks? For most of us retail owners of AVXL shares our losses will be in the tens of thousands of dollars when Anavex goes bust. But for the stock funds, they own millions of dollars of the stock. Gonna be big losses for them. They're probably not as smart or informed as all of us who post here are, right?

So what. How do they compare?

Do you mean to imply that not only are there other sigma-1 ligands, that might be "agonistic," but they have produced clinical data showing that they are better than the data from blarcamesine?

Again, I invite the posting of such data. Convince those of us who have actually scrutinized and understood the cellular chemistry of blarcamesine that blarcamesine won't cut it; won't be approved by the TGA or the FDA; and the any of the other sigma-1 ligand molecules will.

Most readers here strive to make the best equity investment decisions. Help us out. Show the data that show the other sigma-1 receptor molecules to be better than blarcamesine. I've got a lot of money tied up in my AVXL position, continually evaluating all appropriate data and info. Show me, with real, published numbers, that blarcamesine won't beat your "other S1 agonists."

The investment game is not won by merely noting there are many players. One needs to pick the winners of the tournament. The published data and information show that blarcamesine will do this. The "other S1 agonists" haven't scored. A few foul balls, but not a one has won a game against blarcamesine.

Obfuscation, clearly.

You're making that up, for whatever reason. Anavex Life Sciences does own blarcamesine, in every respect.

And, please post any data from other sigma-1 receptor agonists that even approximate those of blarcamesine. Sure, there are other molecules that attach to, are sigma-1 receptor ligands. But not a one has either the safety record of blarcamesine, or the profound, multiple disease moderation successes.

No competition.

Then, could you provide some guidance when any or all of those "other" sigma-1 receptor agonists might hit the market, be allowed to be sold? Will that be before or after blarcamesine is approved by the FDA or TGA? For what diseases? Give us a timeline, please. (Or, is all of that also conveniently nebulous and hazy?)

No, 2022, next year.

Really? The company could go bust by the end of 2022? How so? They’ve got “Sufficient cash for >5 years to achieve key milestones,....” (p41, July corporate presentation PDF).

I’ll make a multi-thousand-dollar bet; with myself. By holding my AVXL position (no trading or sell-outs) until the end of 2023 I’m betting that in 2024 I’ll be way ahead; my long-term investment in Anavex Life Sciences Corp will be increasingly more valuable.

To lose this bet, the FDA (or Australian TGA) must reject the approval of blarcamesine for at least three diseases, Rett syndrome, Parkinson’s disease dementia, and Alzheimer’s. Approval of blarcamesine for any one of these will, by 2023, make Anavex a profitable, revenue-generating entity. The AVXL share price, necessarily, will reflect that. The probabilities of all three of the on-going clinical trials going bust are essentially non-existent. Way too much confirming clinical information. The unique MOA (mechanism of action) explains how this single molecule can facilitate such a multitude of favorable clinical outcomes. No other molecule can do this.

Think not, scrutinize the MOA info here, and then try to find anything like it by any other company:
http://www.anavex.com/wp-content/uploads/2021/07/Anavex-Presentation-July-2021.pdf

Anavex owns it; will provide its benefits to a) AVXL shareholders, b) millions of people across the globe suffering from CNS diseases, and c) government (tax-supported) health insurance and health care systems. Cumulatively, trillions of dollars in a decade.

SAVA and ANVS. Why?

This, of course, is the iHub AVXL message board. The best online compendium of Anavex information, just in front of Anavex’s recent update presentation: http://www.anavex.com/wp-content/uploads/2021/07/Anavex-Presentation-July-2021.pdf

To be pondered are the frequent postings laying out (to a minor degree) information on ANVS, SAVA, and a few other equities. Why are those so frequently mentioned on this board? Please tell: are the FDA (Food and Drug Administration) or the Australian Therapeutic Goods Administration (TGA) constrained to approve only a single drug for the CNS (central nervous system) diseases in the Anavex pipeline; Rett syndrome, Parkinson’s disease dementia, or Alzheimer’s disease? How, in any way, does the consideration for drug use of the products of other pharmaceuticals affect or disqualify in any way a future application of blarcamesine by Anavex Life Sciences Corp?

Fact is, the FDA will approve blarcamesine based solely on its clinical results which, based upon all of the pre- and early clinical data, and efficacious MOA, mechanism of action, will be exceptionally good. When they get Anavex’s New Drug Application (FDA), there will be no information presented or considered on any other new drug owned by SAVA, ANVS, or any other company. To get a new drug approved it must either equal or exceed the efficacies of any existing drugs. For Alzheimer’s, there are but a few; all of which provide only the slightest therapeutic efficacy. Blarcamesine has no competition; its therapeutic outcomes for all three targeted CNS diseases will greatly exceed both the existing and in-trial drugs of any other company.

So, why the awkwardly imposing discussions of matters SAVA, etc. on this board? They are utterly irrelevant. They belong on their own message boards. Usefully, I simply skip or delete any such postings I’m burdened with on this otherwise information-dense message board. The Delete key on my keyboard functions wonderfully.

Of course, some are interested in the pharmaceuticals mentioned on this board solely for short-term trading purposes. Who’s going to make a buck this week on any of the several pharmas that appear here? For those readers, my best wishes. Utterly irrelevant to my goals; to make a very profitable long-term investment (not a trading vehicle). I’ll measure my success at the end of 2023—then continue to retain my AVXL position. I don’t anticipate taking any of my profits (share sales) for many years, if ever. I’m looking for two things from my AVXL position: eventually, rewarding dividends, and, then, dispersal of my position to my estate benefactors upon my demise. That’s all “long term.” I disregard the short-term, day-trading stuff; of no use for me. I’m an investor, not a trader.

Best wishes for all.

Where was this (the Anavex PDF) presented?

Online, for any and all to read.

Number of potential blarcamesine users.

For some future Anavex revenues calculations some numbers have to be used. One of the first ones is the total number of potential individuals who will be taking blarcamesine.

In today’s Anavex presentation it was claimed that in the Americas, in 2015, 9.4 million people were living with dementia; in Europe 10.5 million. To be conservative, I’ll presume there will be 6 million Americans and 6 million Europeans taking blarcamesine in, say, 2024; 12 million in the developed world.

Do your own revenue estimations. You will need to also presume some daily cost of blarcamesine. I’ll presume a day’s dose will cost the patient (well, his insurance company or government) $10. For each patient that would be a yearly cost of $3650. For Anavex that would be gross annual revenues of $3650 x 12 million: $43,800,000,000 ($43.8 billion).

I’ll presume that when that happens there will be one hundred million outstanding AVXL shares. The $43.8 billion of annual gross revenues divided up among those shares would be $438 per share.

Take it from there; estimate the value of a share of AVXL a few years out.

But personally I anticipate that blarcamesine (or Anavex 3-71) will eventually be rather universally prescribed in late middle age (45?) as a general geriatric disease prophylactic, taken by hundreds of millions (at say, $5/day). Count the multitude of zeros in those calculations.