Yes, We Will See

Well, this is so important to know. No one else could have explained it so well. It’s all been bio-checked. Thanks.

When Trofinetide gets approved to treat Rett syndrome, it will become not only the SOC (standard of care) preferred drug for the disease (way out in front of any others), but few after that would even consider prescribing or having their daughter take blarcamesine, when it, too, later, gets approved for Rett.

Important things to understand about new drugs (apparently). First to market is not only the best drug, but the only one that would ever subsequently be used; no matter what else....

....such as frequent diarrhea as a side effect. Mothers with Rett syndrome girls will absolutely reject blarcamesine when it’s approved. “Nope, my girl isn’t going to take any of that new drug. Who cares if it has no side effects? First is always best. We are duty-bound to continue with Trofinetide. We’ve learned how to deal with Susie’s frequent diarrhea. It’s a mess, but who’d want to take a chance on some runner-up drug, which the FDA didn’t approve first? Yea, I know, the clinical results show that blarcamesine doesn’t cause diarrhea, and Anavex clinical results claim it has better symptomatic control than Trofinetide, but who could trust the clinical results from a company that couldn’t finish a trial quickly?”

Then, of course, is the revelation that there are but a limited number of dollars available in the equity market for companies selling drugs to treat Rett syndrome. Again, first to market wins. ACAD will get all of the dollars; none will be left over for anyone to take a position in AVXL. Similarly, no stock investor would ever sell her ACAD position and acquire AVXL shares. You only get to invest, once, in a biotech. Can’t sell and buy something else later; no matter how much better blarcamesine eventually proves to treat Rett.

ACAD has this all locked up; Anavex should just walk away from Rett. It will enter the game after it’s started. No chance whatsoever. First in always wins. Anvex; too late to the Rett game.

Great Post. Welcome Back.

Fireman, so glad to have you back. Again, thank you for your informative post on the physician you talked to. Good enough to hear the perspectives from folks like me, a retired advanced placement biology teacher (from which I know and taught human physiology to future physicians, who got med school acceptances and scholarships from the work they did in my classes). But your post today has to be in the Top Ten, over the years, affirming the profound science of Anavex, and why blarcamesine will be approved by the FDA. Don’t take anything from me, I’m just a retired biology teacher. What could I know? The physician who has been inside the FDA drug review and approval process should be listened to.

Doing well? Well, pretty much. I, too, am a ‘fireman,” a certified prescribed fire manager, authorized by my state’s EPA and forestry agency to plan and conduct prescribed fires in prairies and forests. One site for those is at a giant NASA facility, where I work (seasonally, as a prescribed fire manger). NASA is just a great organization to work for. They listen, understand, and seek new solutions to existing problems.

But I can no longer do the firefighting you do, in wildland fires. I have a mild case of hereditary spastic paraplegia (HSP), which started setting in about 12 years ago. I can still walk, but must use a walker. Therefore, I can plan prescribed fires, and effectively direct my NASA team in safely and effectively conducting the fires. But not being able to walk normally is a frustration. No pain; just very stiff legs.

But, sometime in the future, there is a very high chance that blarcamesine will resolve my leg spasticity. It is caused by a deficiency of GABA, gamma-aminobutyric acid, in the long nerves that control my thigh aductors. GABA retards, slows over-excitement of nerves. Without it, many nerves constantly fire; hence the spasticity.

But, as the early studies in girls with Rett syndrome proved, blarcamesine induces normalized production of GABA — safely. As I’ve contended before, the “undisclosed” rare disease that Anavex may target may well be HSP. For me, it would be very helpful. But for those with complicated (massive) HSP, it will be stunning.

Also, I work at a university research foundation, where my research team, using biological processes I identified, is solving some very significant ecological problems. Just like Anavex science, a new, unique approach that will change things.

An Opportunity.

Thanks for posting this. Exactly what would be expected, from a real professional working in or with the FDA.

Yes, all of the clinical outcomes from blarcamesine being tested in real humans (Phases 1 and 2) have been extremely positive; without adverse events (side effects), even. There is no reason, no apparent mechanism by which the results (to be announced) from the big, long, statistically-valid Phase 3 trial will be any different. They will only substantiate what has already been discovered and demonstrated.

But, now an opportunity. We'll all be delighted to ponder and scrutinize postings that can tell rather specifically how and why the Alzheimer's Phase 3 results will fail, preventing the FDA from approving the drug. Please, tell us how and why the Phase 1 and 2 results won't or can't be replicated in the big Phase 3. This will be a wonderful chance for various posters to set things up for an "I told you so!" pronouncement when blarcamesine fails. Let's hear just how it will fail in the Phase 3 study. Inquiring minds want to know, right now. Experts here should be able to tell us. Please.

No, End the Games

Actually, with the release of the Alzheimer's clinical trial results there will be no more games. New rules, all defined by the results. For the last many years, lots of games regarding Anavex, all thoroughly (but not always accurately) described on this message board

The play by play (well, day by day) narratives of the Anavex drug approval games have been, at least, interesting. Anavex naysayers have laid out all the reasons the company has and will fail. Others have followed and described the known science of the Anavex sigma-1 receptor activators and have laid out great futures for the company and the millions of patients with various CNS diseases.

Let the games end. As they will, let the clinical results speak for themselves.

Blarcamesine will self-market itself.

Perhaps.

But, in fact, that may not be necessary. The clinical data themselves will spontaneously tell the then-validated Anavex story.

All of the “deficiencies” in previous blarcamesine clinical studies and results will be missing. First, this Alzheimer’s study was big, not thirty or forty participants; big enough that data are statistically reliable and valid. Previous Phase 1 and 2 studies could be dismissed as non-predictive; not enough participants; and, perhaps, not long enough. This trial is big (large N) participant number, and lengthy; long enough that results can’t be by mere happenstance.

And that will all be revealed by the P-values. In conventional, accepted biostatistics, to be valid (and accepted), results mustn’t have a greater chance of mere happenstance, chance results of any greater than 5%, one in twenty. The P-value must be 0.05 or less. Any results larger than 0.05 will disqualify whatever is being measured.

So, what if all of the P-values are <0.05? Simply, then, blarcamesine works; is a viable, useful Alzheimer’s disease therapeutic. No more questions, other than when and how can Alzheimer’s patients start their Anavex therapies?

Unlike Aduhelm, with its untoward brain swelling as a major “adverse event,” side effect, blarcamesine has never, in any of its clinical studies, whether in murines (lab rodents) or real humans, produced adverse events (AEs) of any debilitating consequence. The drug is profoundly safe; uncommon in drugs acting in the central nervous system. The clinical results will not reveal any disqualifying AEs.

So, what results can be problematic for Anavex? Only where symptoms have failed to be controlled, slowed or reversed, by blarcamesine. If blarcamesine is a failure, patients with Alzheimer’s taking it will, over the lengthy treatment period fail to show any improvements. That’s why big clinical studies must have two “arms,” test groups. About half of the study participants will have taken what they think is the drug, blarcamesine. The other half, too, will take what they think is the drug. But the study is “blinded.” The people actually taking the drug, in the “experimental arm,” will get the real drug. The other group, in the “placebo arm,” will take pills that look exactly like the real drug. But those pills will be primarily colored starch, the placebos. No one knows whose taking what until after the trial is completed (just recently). Then, computer coding will unblind the results, the two trial populations will have their results compared.

And that’s what will make big articles in major papers. “New Drug Shows Safe Efficacy Against Alzheimer’s.” Nothing more need be said. Every Alzheimer’s stakeholder, doctors, patients, care-givers, health insurance companies, etc. will scrutinize and devour the outcomes from the study. All of the articulated Anavex naysaying encountered on this stock investment message board in the last seven years will quietly fade into destined oblivion. Press releases from Anavex Life Sciences Corp will be fine. But even without them, the blarcamesine story will be globally validated. A new era in Alzheimer’s therapy, understood by all.

Give Zen My Regards.

Well, I actually don't know this Zen guy. He must have things altogether.

But I do know cellular biology rather deeply, as good as any first-year med school student (well, probably better). I had to teach it to talented advanced-placement biology students enrolled in my classes specifically to gain admission and scholarships to pre-med and other advanced biology college curricula.

It's the demonstrated, tested Anavex science that directed my investment in an AVXL position. Most are not able to adequately understand the unique, facilitating details of the mechanisms of action (MOAs) and how they produce both the demonstrated and anticipated clinical results against, of all things, recalcitrant central nervous system (CNS) diseases.

What? This biotech startup thinks it can actually treat either Alzheimer's or Parkinson's disease? Get real. For Alzheimer's, they aren't even targeting either the beta-amyloids or tau plaques. The entire medical world knows that the only way to solve Alzheimer's is to chemically force the body to remove those waste proteins. Anavex, however, claims that by allowing its small molecule to stick to a little-know protein, the sigma-1 receptor, all sorts of consequent good things happen in neurons.

Today, I'm a scientist in university research program. Professionally, today I specialize in a particular sort of plant ecology, where I and my research team are implementing (with a federal grant) a new habitat clean-up protocol that I devised. Too detailed (and irrelevant) to describe here. But as a research biologist I always want to understand the biology back-story of new ideas or concepts. When I learned of Anavex I wanted to see if there was anything to what they were claiming. At the start, sure seemed bogus.

If you didn't know or understand cellular physiology or related morphology, the Anavex science makes no sense. But when I read the journal article papers on the Anavex drugs acting in animal models of human CNS diseases, I understood. Nothing bogus at all. New, previously unknown cellular chemistry, all connected to the sigma-1 receptor protein and its various cell-keeping functions. Great stuff, eventually to be commonly recognized when the FDA approves blarcamesine for clinical uses, sometime late this year or in 2023. I'll patiently wait.

Nope. Disappointment Not In the Picture for Me.

No. Be assured, my taking of a moderate AVXL position in the last five years is not a matter that if resolved poorly (if Anavex goes bust) will cause any "disappointment" or other anxiety on my part. The dollars I used to buy my AVXLs have been dutifully erased from my costs of living budget; knew from the start that there was no guarantee that I'd ever recover their costs. Anavex Life Sciences Corp is a start-up biotech, with not a single product (yet) to sell. No revenue sources; just an awful lot of solid science indicating that drug sales will happen, when the science (of the 3 big clinical trials) is recognized by the FDA. After that, every anticipated thing comes into place ... including share prices >$2000 some years out. I can wait, patiently. I've got many good, productive things that keep my mind occupied. Not worried, concerned, or anxious about my AVXL position. Other things in life far more significant.

Well, yes, a form of greed.

If that’s what you wish to label long-term investing, you are welcome to. Merely a matter of investment period perspective. Some invest in equities with a day-to-day perspective. Buy on cheap days, then sell on high-price days. Day-trading. Quite legitimate. Apparently, some who post on this message board do this expertly. Congratulations.

Then, there are seasonal and annual stock investment perspectives. “Sell in May, and walk away,” is one seasonal investment dictum. Equity investment time frames are moderate, in months or a few years.

But those of us who do not anticipate selling any of our AVXLs when the share price touches or exceeds $2000 have a long-term, even generational perspective. We anticipate that our AVXL positions will rewardingly pay off in dividends. Those will be our annual AVXL investment returns. And yes, within a decade, with annual global sales revenues in the many billions, the AVXL share price may well exceed $2000. Personally, I’m not interested liquidating any of my position at any price. At $2000, that would be authentic greed; I’d have to pay taxes on the many millions of long-term capital gains taxes. Of course, I’d have millions of dollars of cash in my bank account; but what then?

No, I’m planning for, hoping for eventual AVXL share prices >$2000. My holding will reside within an estate trust. My wife and I will live well enough from the dividends. But upon our demise the estate will distribute the shares to the estate’s beneficiaries, our children and worthy relatives, and to a diversity of philanthropies.

With that arrangement — should it occur (the high share prices) — everyone will benefit. Praiseworthy “greed,” if you will. Hoping that it happens.

No, "the body" won't become "resistant" to blarcamesine.

Ok, understood. Thanks.

If this is a problem with blarcamesine, it means that "the body," the sigma-1 receptor protein, would no longer be activated by blarcamesine when it "gets used to it."

Not a factor here. The sigma-1 protein cannot in any way "learn" to reject or in any way repel the attachment of blarcamesine molecules. Simply, by the laws of chemical reactions and molecular physics an available blarcamesine molecule will necessarily attach to, bind to the sigma-1 protein. Thereafter, the protein is activated and all of the downstream reaction cascades and processes must necessarily follow.

Important distinction. Blarcamesine is not in any way a conventional drug. It works entirely differently. In fact, when present, nothing can stop it from working, from restoring or facilitating normal cell-keeping processes; the ones that suppress various disease states.

Endurance of Induced Prophylaxis

Thank you; important information from the Phase 1 study.

The question yet remains, to be answered in murine studies, would spaced-out dosings of blarcamesine, at low dosages actually provide prophylaxis? Worthy of testing is the hypothesis that very low doses, taken at lengthy intervals (say, once every Monday) might actually be, over time, prophylactic. Although the half-life of the molecule might be 4 hrs, its promotion or facilitation of normalized cell physiology might well be enduring. The real question is not the half-life of the drug; rather, the half-life (or endurance) of any induced prophylaxis. Two different things.

(I'll bet Anavex, from murine studies, has a handle on all of this. Might have allowed Dr. Missling to make his off-hand comment about eventual prophylactic uses of blarcamesine.)

Drug Tolerance Not a Factor

Really? Please post information supporting this conjecture. I've seen no data supporting the notion that diseases could in any way become tolerant of blarcamesine.

Clearly, microbial diseases, whether bacterial or viral, by natural selection can become tolerant to various chemotherapies. Quite common with antibiotics. Happens with viral diseases, too. Mutations in the causative microbes change them enough that the antimicrobial drug is no longer effective. In every such case, there is a mutation or variance in the genetics of the pathogenic microbe.

But there are no such microbes in any of the CNS diseases Anavex is targeting. There is no known mechanism by which Alzheimer's disease could become "resistant" to blarcamesine. Alzheimer's is not an infective microbe with genetic variances that could yield tolerance or resistance to blarcamesine's restoration of homeostatic or protein-folding processes.

Blarcamesine Dosing for Prophylaxis

I, and others, have posted messages theorizing that blarcamesine (Anavex 2-73) will be used not only to treat existing cases of various CNS diseases but also will be prescribed and administered for prophylactic purposes, where the drug is taken before any disease symptoms appear, so as to prevent their onset. Disease prevention; prophylaxis.

Important question: what dosages and dose frequencies would be required to attain prophylaxis? Would they have to be at the same level and frequency as required for an existing disease state? Or, could prophylaxis be functionally attained at far lower doses, taken less frequently?

I’m certain that Anavex has investigated and knows the half-life of a dose of blarcamesine. If it’s short, say 8 to 4 hours, daily dosings, perhaps twice a day would be required to maintain functionally useful systemic concentrations.

But what if the functional half-life of blarcamesine is 24 hours or longer? Because it’s a sigma-1 receptor ligand, it chemically binds to that protein and may stay functionally attached for extended periods. For prophylaxis, it’s very possible that smaller doses, at more lengthy frequencies will be sufficient. Instead of taking a 50mg tablet of blarcamesine each day (a presumed dosing regimen for an existing CNS disease), for prophylaxis merely 20mg, taken twice each week would be effective. Ideally, a small dose taken every Monday morning would prevent the onset of various CNS and other diseases.

“Good morning! This email is from your friends at Anavex. It’s Monday, so be sure to take this week’s blarcamesine capsule.”

Monday’s become the Stay Healthy Day of each week.

Short-term trading, or long-term investment?

Well, I’ll speak for myself, representing I’m sure a good percentage of long-term holders of AVXL positions.

“Married” to the stock? Nope. For me owning a stock like Anavex is a long-term investment decision, where I know that the company is a biotech startup, without any revenues until it is able to sell its new drug. And that can’t happen until the FDA gets positive clinical outcomes validating the drug’s efficacy and safety. By definition, long-term stock investments can take a long time to pay off.

I’m not married to Anavex, but I’ll continue to hold my AVXL position on out. If all three of the big clinical trials fail (Rett syndrome, Parkinson’s disease dementia, and Alzheimer’s disease), my entire investment will be lost. But, if even just one yields positive safety and efficacy results, Anavex Life Sciences Corp will be, soon enough, a very profitable, revenue-generating corp. At this very moment, shares of AVXL have traded at $10.70. The cost basis for my several thousand AVXLs is $2.91, the value of my holding has increased 3.6x. With FDA approval for any one of the three diseases, the share price will quickly go to $30, then continue to ascend for the foreseeable future. To $1248 or something? Who knows? I’m not concerned. It may level out in three or four years at $500. Or, $2000. Either way, I’ll be way ahead (well, my estate will be).

If holding, taking, and selling AVXL positions are elements of a stock-trading scenario, then the question of when would a position be sold out is useful and legitimate. But, for me, not at all. Actually, if some Big Pharma tried right now for an Anavex buyout at, say, $2000 per share, I’d vote against it (giving up several million immediate dollars). I’m looking out at least five years, then ten; when Anavex Life Sciences Corp will be a major global pharmaceutical, selling a pharmacy-shelf full of new drugs, yielding for me and my estate beneficiaries very significant annual dividends. That’s “long-term investment,” not short-term day-trading. Two different, contrasting stock investment approaches. Both are valid. For those day-trading AVXLs, my best wishes. But, if I have Anavex science right, I’ll be glad in 2032 to compare any Anavex day-trading revenues with what my position will be both worth and what it will be yielding in dividends.

I’m not “married” to Anavex. Nor have I jeopardized any of my family budget in acquiring my AVXL position. Over the years it’s been purchased solely with discretionary funds in my budget; dollars left over after all financial obligations have been met. Either way, with an Anavex bust (totally bad clinical results), or with phenomenal results (with massive share price ascents), my life will go on. I come out either even (no gains), or with gigantic value increases. The use of the few thousands of dollars I used to take my AVXL position has already past. Right now, functionally I’m “even.” In a few years? Check back. Not a shred of clinical evidence, whether murine or human, indicates Anavex will fail in any of the three clinical trials. I don’t anticipate that I’ll ever sell any of AVXLs. At my death (perhaps delayed because of blarcamesine prophylaxis) they will pass on to my estate beneficiaries. My wife and I will have to live ever so meagerly off Anavex dividends. If Anavex goes bust, my teacher retirement payments will have to suffice.

Yep, precedent must prevail.

Then, of course, when blarcamesine is approved by the FDA to treat Alzheimer’s or Parkinson’s, no health insurance company is going to pay for blarcamesine until client patients have full-blown symptoms of dementia. Prevention is just out of the picture, because someone said it will never happen, and there’s no precedent. Medicine only does things that have been done previously. That fact has now been biochecked.

Medicaid or Medicare won’t ever allow prophylactic uses of the drug, either. They’d prefer to let people get the diseases first, then retroactively treat them, hoping for the best. (Just what was that Dr. Hagerman thinking of?) They gotta spend those millions of dollars in their program accounts; best to spend it only on people with developed, severe symptoms.

Economically most important will be the lobbying by the nursing home/medical care industry. In the coming decades tens of millions of aging Americans are destined to suffer from Alzheimer’s and Parkinson’s, requiring long-term personal care. Being able to prevent those diseases will be the ruin of an entire industry. “...the total cost in the United States associated with Alzheimer's disease for 2021 is estimated at $355 billion. Medicare and Medicaid is estimated to pay for $239 billion of the costs.”
https://curealz.org/the-disease/stats-and-costs/

“Precedent” must prevail. We just learned it here, from an expert in the medical care and insurance industries. Although hundreds of billions of someone’s dollars could be saved, prophylactic uses of blarcamesine ain’t never gonna happen. Ya read it here first. It’s been biochecked. We can sleep better tonight. The medical care industry will be preserved.

Then, even bigger things to follow.

What will be convincing at the FDA will be the actual positive therapeutic outcomes from the three on-going (soon to be completed) human clinical trials. The clinical data will demand an explanation. Just how could Anavex's molecule, blarcamesine, have produced such positive results, when compared to existing drugs?

There won't be a mention of immunogenic removal of waste proteins, the Aduhelm mechanism of action (MOA). No reference to how Aricept slows (but does not stop) symptomatic progression.

Actually, the only two things the FDA needs to discover is if the drug provided therapeutic outcomes as good or better than SOC (standard of care) drugs; without untoward side effects. With those results, approval to sell and clinically utilize blarcamesine will happen.

But others will have to explain how Anavex succeeded. The FDA needs to know only that the drug worked, safely. The exact mechanisms of those successes don't have to be explained by the FDA in their approval announcement. Those will have to be provided by both Anavex itself, and the medical press. "New drug, with new action, approved to treat Alzheimer's." The medical press will have to go back and scrutinize the graphics and diagrams on the Anavex website. It's all there. They'll be saying pretty much what I just said in my first post. But it will be no longer conjectural. The clinical results will have validated the mechanisms.

Then, on to other diseases and conditions, with the other Anavex drugs. Anavex 3-71, I contend, will be even more important, safe, and effective, for an expanded spectrum of human diseases.

But eventually, the final Anavex Big Story will be the widespread use of Anavex drugs for prophylactic, disease-prevention uses.

And, it's safe.

I failed to mention in any way the utter safety of the Anavex drugs. Almost all of the drugs acting in the central nervous system have side effects of varying degrees, "adverse events" (AEs).

In any of the clinical tests of the Anavex sigma-1 receptor drugs, whether in murines (lab rodents) or in real humans, no obviating AEs have ever appeared, An infrequent circumstance among brain-acting drugs. Another Anavex positive.

Why Anavex Is Different

A consideration of how and why blarcamesine (Anavex 2-73) and Anavex 3-71 are markedly different CNS and other disease therapies.

First, the two major disease therapy targets for the Anavex drugs, Alzheimer’s and Parkinson’s diseases, are diseases or conditions that present themselves, have their onsets later in life. In most cases, people with the targeted diseases were in health in the first portions of their lives. Then, at middle or older age, any of the various disease symptoms appeared. In regard to the unique mechanisms of action (MOAs) of the Anavex drugs (which, among other things, are sigma-1 receptor protein activators), this is extremely significant.

Let’s start with Alzheimer’s disease. Twelve-year olds don’t get the disease. A very few, with a particular genetic propensity get it starting in their twenties or thirties. The vast majority first experience the disease’s symptoms after middle age, starting in the fifties, sixties, or seventies. Most commonly, Alzheimer’s is a geriatric disease, occurring in older people.

The same is true for the various forms of Parkinson’s disease.

With this typical scenario of symptomatic initiation, how can the Anavex drugs work, particularly in comparison to recognized and commonly used SOC (standard of care) drugs? Will the Anavex drugs treat these CNS (central nervous system) diseases the same way as conventional, existing drugs, or not?

Very much, not.

First, a diagnosis of either Alzheimer’s or Parkinson’s disease is ominous. Conventional, available treatments can only slow the lethal progression of those diseases. And most often, not very successfully. Simply, none of the existing drugs are able to effectively or safely restore a youthful, healthful state of neuron (nerve-cell) physiology. Although some welcome treatment outcomes may happen, the underlying, causative neuropathology lethally continues. Existing drugs for Alzheimer’s or Parkinson’s inevitably fail. Patients die.

How, then, could this be different with the Anavex drugs? How could they terminate or chronically suppress the disease-causing biochemical anomalies in each of the two big CNS diseases? No other drugs have been able to do this. Specifically, how can the Anavex drugs make this happen?

The key? Unique, propitious activation of the sigma-1 receptor protein. Anavex 2-73 (blarcamesine) and Anavex 3-71 easily cross the blood/brain barrier, enter neurons, and then bind to the sigma-1 receptor protein on the surface or edge of the endoplasmic reticulum. With that, all sorts of good things are initiated in the neuron.

When properly functioning or activated, the sigma-1 receptor protein (the Sig-1R) modulates, controls a diversity of processes within the neuron. “...Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in living systems.”
https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(16)00004-3.pdf

Simply, activation of the sigma-1 receptor by the Anavex drugs fixes bad things happening in diseased neurons. They restore “homeostasis,” the ability of the cell to properly control its biochemical function in a steady state, the “homeo-” process.

In the case of neurons with Alzheimer’s or Parkinson’s, homeostasis (“same status”) no longer occurs. In the case of Alzheimer’s, waste proteins, beta-amyloids or tau plaques, accumulate, disrupting normal nerve cell signaling and operation. Alzheimer’s symptoms result (cognitive impairment, etc.). In Parkinson’s, other biochemical disruptions occur — all because neurons can no longer work as they did in more youthful years. Activation of the sigma-1 receptor by either of the Anavex molecules restores normalized homeostasis.

One of the most important and significant outcomes of Anavex sigma-1 receptor activation is the proper folding of various enzyme proteins. Virtually every chemical reaction within a living cell is controlled and modulated by a specific enzyme. Enzymes are proteins, complex and detailed key-like structures. Like a key, if they get bent out of shape (as can happen in older age), they can’t catalyze chemical reactions. This happens in neurons being clogged with beta-amyloid waste proteins. Normally, enzymes are synthesized in ribosomes, then bent into their proper shapes. Simply, properly-activated sigma-1 receptor proteins modulate, facilitate proper enzyme structures. With that, waste-clearing enzymes are active and waste proteins cannot accumulate and cause the symptoms of Alzheimer’s. Similar processes are involved in Parkinson’s.

Propitious activation of the sigma-1 receptor facilitates a diversity of other good cellular functions, too lengthy to describe here. But in each of these outcomes, uniquely, they are controlled upstream, at the start of reaction sequences or pathways, thereby making “downstream” functions work. This is exactly why the Anavex molecules are so effective. Instead of trying to fix already broken things happening “downstream” within the neuron, they fix wrong things at their start, at the upstream, top, or start of reaction cascades or processes.

To certain degrees, this also works with genetic anomalies present at birth, such as the horrible symptoms of Rett syndrome.

As the story of the Anavex molecules begins rapidly to become recognized and depicted, notice the universal involvement of the Anavex drug’s activation of the sigma-1 receptor protein. That’s where the remarkably phenomenal therapeutic results will emanate from. Propitious activation of the sigma-1 receptor protein is the Anavex story. This year and next, with the completion of the on-going clinical trials (Rett syndrome, Parkinson’s disease dementia, and Alzheimer’s) the world will learn of — and benefit from — the company’s unique, proprietary science.

Looking out....

Big Pharma execs and researchers aren't dumb. They can know just as much as we who post on this message board.

You can bet, a good number of bench-tech Big Pharma PhDs working on CNS drugs, who have been following and understanding Anavex science, have started to look for new positions, either in-house, or at other research facilities. They, too, can see that the days when Big Pharma and all of the medical world targeted waste proteins (beta-amyloids, tau clusters, etc.) are rapidly coming to an end. On out, it'll be the sigma-2 receptor, and Anavex has that locked up.

Edison and Adams

Wow! How wonderful was that?

Yes, Ansel Adams, another who thought beyond and outside of what "was known." Pretty much self-trained as a photographer. One of the greatest.

I've done thousands of photos of biological and geological subjects, across the continent, for the many digital programs I present on biological topics. In fact, I wonderfully apply Ansel Adams's zone mapping to many of my photos, with digital re-processing. HIs concepts turn gray-blah photos into stunners.

As for Thomas Edison's influence on me, he began my interest in science. In the fourth grade, when I was struggling with school (got put into school too early, was developmentally behind; had very poor grades) Mrs. Stuckey, my fourth-grade teacher took our class on a field trip to Edison's birthplace. There, I bought a paperback biography of Edison, written for children. I read it, and believed if Edison, with his perceived mental deficiencies could go on to success in science, so could I, From that day forward, I decided to be a "scientist." Fruitful inspiration.

No, "bad" science is the "problem."

No, the professional world's inattention to Anavex, whether in medicine or investing, is "denied" by the fact that Anavex's approach to treating CNS diseases is entirely outside the professional world's knowledge base of what's real. Some obscure sigma-1 receptor protein ligand can fix CNS diseases? Get real. Nothing about it in any medical textbook; just tau and beta-amyloid protein agglomerations. The professional smart people know better.

Credentials? Or performance?

First, thank you for your comments; understood and appreciated.

In regard to your father, a veterinarian, he, too, was somewhat disregarded by "real physicians." But, actually, physicians are veterinarians, too; but they are trained to treat only one animal, humans.

In my case, I continually detect among my more distant research associates at the university research foundation where I conduct some very leading-edge ecological research their questioning of my position. I'm "just a retired advanced placement high school biology teacher," without advanced degrees. I have no business doing the research I'm doing, or getting big grants for it.

So be it. Thomas Edison, in school, was an absolute failure. He never even graduated from high school. But, because of his ideas, research approach, forbearance, and phenomenal ideas and understandings, he changed the world.

His greatest invention was not the light bulb, sound recording, or motion pictures. Far bigger --- the modern research and development laboratory. Before Edison, inventors locked themselves in closets and kept their ideas and devices secret, until they got a patent. Edison did exactly the opposite. At his new Menlo Park lab, he invited, hired, all sorts of people; without regard to earned degrees. Instead, he wanted around him people with new, good ideas, and the desire to test and prove them. His team shared ideas; kept little secret.

He even asked the wives of his workers what they'd really like his team to invent and develop. What could they "know?" Well, from them came sound recording. They said, "If only our daughters had talking baby dolls!"

The rest is history.

Similar things are happening at Anavex Life Sciences Corp. "Known" and "accepted" understandings of various central nervous system diseases are being discounted. Innovative, new, perspectives are being encouraged and used. Before Anavex, "sigma-1 receptor ligands" for human diseases were essentially unknown. For Alzheimer's, biochemical removal of the tau and beta-amyloid proteins was the ONLY thing that would work --- so said the experts. Well....

Diversities of ideas, trainings, and approaches. With those diversities, things that actually work will arise. The only thing that counts is performance. By the end of the year, we'll know how blarcamesine works in people with Alzheimer's. The drug's curious, "unlikely" mechanism of action will have been validated. Who would have thought? (Many of us here, actually.)

Schwab, too.

Charles Schwab states that at 4pm 1,075,276 AVXL shares had been traded during the day.

Schwab, too.

Schwab, too, has 1,075,276 listed as Anavex's trade volume for the day.

No Genetic Correction, But Possible Moderation

Good question: could Anavex 2-73 (blarcamesine) be used to prevent the expression (working) of pathogenic genes, as in the case with Fragile X?

I don’t know. Fragile X is sex-linked, meaning that the pathogenic gene (FMR1) is located on the X chromosome. An individual with two X chromosomes, one inherited from the mother, the other from the father, is a female. Males have a single X chromosome, inherited from the mother (she can only donate X chromosomes, she has two). The other sex-determining chromosome is the Y, inherited from the father. It is the random selecting of the father’s sex chromosomes, X or Y, that determines the sex of the child, at conception.

Hence, the predominance of Fragile X syndrome in boys. They have only one X, from the mother. If it’s one with the FMR1 gene, the boy will have Fragile X. In the case of girls, two X chromosomes. If either one of them has the bad gene, the disease is expressed, occurs.

When the FMR1 disease-causing gene is present, could Anavex 2-73 keep it from being expressed, preventing the onset of its symptoms? I don’t know. Seems unlikely.

But, as the early clinical trials show, the drug may well be able to moderate the severity of the untoward symptoms; making the disease less severe. Let’s see how this works out in humans with the disease.

It was asked if the drug could be used “in pregnancy” to correct the chromosome X genetic defect. Too late. The mutation, creating the bad gene, happens long before pregnancy; sometime during or even long before spermatogenesis (sperm formation). But, there, the Anavex drugs may suppress bad mutations, making eggs and sperm genetically “pure,” without bad mutations. If that’s the case, dosing with Anavex drugs would have to be early, particularly in females. Actually, genetic oogenesis, egg formation, actually occurs very early, even before birth. So a woman would have had to take blarcamesine while she was yet in utero. Well, her mother would have had to take it.

But, far greater....

Yes, especially with the additional implementation of Anavex 3-71 therapies.

But, eventually (several years from now --- too long for quick-buck traders to contemplate) both Anavex sigma-1 receptor activators, Anavex 2-73 and 3-71, will be proven to not only "fix" (meaning, treat) various CNS and other diseases, but they will prevent or markedly delay the onset of a host of diseases. Prophylaxis.

If administered early on, the drugs' disease "fixing" mechanisms will fix the pathologies before they become manifest. In every case, prevention is better than treatment or cure.

Ten years from now, health care insurance companies (and policies) will pay for and mandate periodic prophylactic Anavex drug dosings. Health care will be revolutionized. (The share price of AVXL will be >$2000.)

My opinion? Sure. In 2032, check back with the beneficiaries of my estate. They'll be both healthy and economically secure.

Draw One's Conclusions

Thank you for posting this abstract; which especially includes this excerpt:

The reader, depending on his understanding of the technical terms, and as shaped by any particular understanding of the greater Anavex science, will discern the significance of the presentation (when it occurs).

Anavex 3-71 was administered to trans-genic rats (rats with the genes for Alzheimer's) to determine if favorable slowing or prevention of behavioral symptoms occurs, and if so, does this persist after dosing is terminated.

Simply, Anavex 3-71 persistently prevents or even reverses the progression of Alzheimer's symptoms in rats with the human disease. With no mention or discovery of adverse events (side effects).

Once again, an Anavex drug that is safe and effective, with the same mechanism of action (MOA) at the sigma-1 receptor protein as blarcamesine (but at markedly reduced dosages).

Carcinogenicity Won't Be A Factor

Tests for carcinogenicity (cancer-causing) and genomic disruptions are standard preclinical tests for proposed new drugs, conducted in a host of organisms. If they haven't been conducted and their results are not available to the FDA, chances of a New Drug Approval are essentially nil.

The Ames Test is the first one, followed by lower animal exposures of the proposed drug, such as tests on Caenorhabditis elegans, a common lab nematode. Then, long-term tests in animals (lab mice, rats). Finally, there is the monitoring of any genomic disruptions (mutations, changes in DNA) in the Phase 1 human trials.

Search all of the literature on blarcamesine in organisms, whether bacteria or animals. I've never seen a single discovery or incident of blarcamesine-induced or -associated carcinogenicity or induction of mutations of any sort. If any are published, please post them.

To the contrary, blarcamesine's favorable modulation of gene expression by its enhancement of chromatin functions tends to obviate against the aberrant mechanisms involved in the genetics of neoplasms (cancers). The FDA review board will be impressed with the absence of evidence or incidents of any carcinogenicity related to blarcamesine.

Actually, many approved drugs are known to be associated with or to induce cancers. Nonetheless, their therapeutic benefits outweigh the infrequent hazards of the drug's cancers.

Stunning.

Wow! Thanks for posting this, for this women, 41, who has been disabled by Rett syndrome all her life, who with blarcamesine treatment exhibited these improved behaviors.

Will blarcamesine get approved for Rett? Could any of the above be definitive of blarcamesine’s efficacy for the disease in older victims, such as Tanya, here? Anyone want to tell us that we can’t really know; that any or all of this can be merely a placebo effect?

Imagine, then, how Tanya might have fared had she been able to take blarcamesine from the day she was first diagnosed, at birth or right thereafter. Could the drug have been able to prevent or suppress the neuromuscular debilities that so much afflict her?

Once again, it must be understood that most drugs working strongly in the central nervous system have a multitude of untoward side effects; often as bad or worse than the symptoms being addressed by the drug. This has never been the case with blarcamesine, either in numerous murine (lab rodent) trials, nor in any of the existing human trials.

Safety and efficacy. For Rett, blarcamesine continues to succeed.

No Concerns

I, too, have been buying AVXLs since 2017, in small incremental lots. Yes, the share price has been up and down over that time. Today, the share price, like the market itself, is trending down. Right now, I have it at $7.70. My holding is worth 2.6x what I paid for it. I’m settled and satisfied.

But let’s check back at the end of 2023. Or, even better, at the end of 2026, when millions suffering from various CNS diseases are being successfully treated with blarcamesine.

Now, or then?

Gator, thanks. You’ve spoken for a larger number of us with long-term AVXL positions; as opposed to the quick-buck in-and-out crowd.

Generally, those of us who post on this board fall into one of three general categories. One, the short-term trade to gain group. Two, the long-term investment group, who see that their AVXL positions will be very profitable in several years, after the FDA grants approval for at least one CNS disease. Three, the bad-management naysayers lambasting the CEO.

Personally, I can’t comment on the quick-trade group; it’s not what I do in the stock market. I have no expertise or confidence it that scenario. Postings on such have no relevance to me, so I click on the next posting. For those who successfully engage in trading AVXLs, congratulations.

Same for the bad management postings. Those have no relevance to my AVXL investment perspective. Missling doesn’t create Phase 3 clinical trial results. They come from the trials themselves, not by some managerial edict by the CEO.

But many, probably most who have AVXL holdings and read the daily postings on this informative message board have taken into account two considerations. First, Anavex is a biotech start-up, with novel, yet to be proven (Phase 3 clinical results) data; but supported by extremely strong pre-clinical data, in both murines and humans. Therefore, we’ve taken our AVXL positions knowing there is a slight possibility that something untoward might eventually turn up and terminate the company. Therefore, we’ve invested dollars we can afford to lose.

Very likely, however, the clinical results from the three big trials, Rett, Parkinson’s disease dementia, and Alzheimer’s, will be overwhelmingly positive. With those, in a few years, Anavex Life Science Corp will become a major pharmaceutical. In five to ten years, our moderate AVXL positions will have appreciated by orders of magnitude. We can patiently wait.

Give us further guidance, please.

Well, thanks. So helpful (maybe).

If you would, as an investor, please guide us specifically on how any of us should regard any or all of the published research data on blarcamesine. So far, all of it is "preclinical," in the sense that the drug has not yet gained regulatory approval for sale or therapeutic uses in any humans.

Should the existing published research data on blarcamesine, in both animals and humans, guide us in any way about taking an AVXL position? The published data look pretty good. Or, should we just discount those research data and wait around until the FDA approves the drug? Or, in the middle, take a small AVXL position, knowing full well that the drug's approval is yet contingent on the favorable completion of Phase 3 clinical studies?

That's what I've done. Over the years I've incrementally bought small numbers of AVXL; now own a few thousand shares. If my personal enthusiasm is not borne out in eventual FDA approval, my investment will be lost. On the other hand, if blarcamesine plays out as I believe the existing research data portend, I'll be worth several million US dollars. I'm comfortable with my position's risk/reward profile.

On the other hand, if I were to have in hand as cash the dollars I've used to acquire my AVXL position, and then take a new position after FDA approval, my eventual position value would be but fraction of what I presently envision. Buy early and cheap, and wait? Or, wait and buy late, with far lower eventual returns?

Differing biostock investment strategies. For me, the copious data from existing papers on blarcamesine research, which are virtually all positive, has directed my particular approach. We'll all see if this has been effective when the FDA makes a blarcamesine decision.

Eventual veterinary applications.

Of course. Most of the drugs that work in humans also work in animals; such as antibiotics.

Except by me (previously, some time ago), there has been no mention of blarcamesine's potential utility as an animal therapeutic. But, just as with what happened with antibiotics in the 1950s, sooner or later blarcamesine will be tested and applied for veterinary and animal husbandry uses. Gigantic market.

Check back when human trials are completed.

Well, isn't it curious that Dr. Hageman made for blarcamesine against Fragile X essentially the same claims I did? Who' ya gonna believe? Dr. Hagerman, a recognized, experienced expert on Fragile X sees in blarcamesine the same things I do. But she sees them in both the knockout mice in the journal letter, and in the Fragile X subjects she conducts research on.

The original poster claimed, "This is nonsense of course, and particularly errant from "a biologist." Actual biologists would not make such a definitive statement from any animal model."

Oh, Dr. Hagerman is not "a biologist." Really?

Of course, the blarcamesine naysayer so conveniently neglected to mention that I also said all this needs to be demonstrated in a proper clinical trial with drug in real humans. When that happens, let's see who was correct, Dr. Hagerman and me, or the poster who claims that Dr. Hagerman is not a biologist.

For a variety of reasons, many are certain that any and all of the pre-clinical studies of blarcamesine, whether in transgenic rodents, or in humans, are necessarily flawed and cannot in any way predict therapeutic successes in real humans. Those with that perspective are welcome to refrain from taking an AVXL position; even to proclaim (vividly or otherwise) why they don't. Others of us see eventual blarcamesine success, based upon what we believe existing evidence (in both murines and humans) shows and adequately predicts. We've taken our early AVXL positions before that share price multiplies. A difference in stock investment perspectives. Let's see how that plays out when Fragile X trials are complete for humans. Again, them's the only ones that count.

Merely a letter. Next, clinical proof.

Well, I couldn’t read the entire letter; was behind a paywall.

First, this is not a research report. It’s a “Research Letter,” to appear in the American Journal of Medical Genetics. The journal received the letter on 26 February 2022, and accepted it on 30 April. So, it’s been seen by a good number of people at the journal. Significantly, the journal editors chose to publish the letter — they thought their readers should learn about blarcamesine and Fragile X.

To some good degree, this seems to validate what the letter states. If the editors thought the authors were stating or claiming questionable things, it would have never been accepted or published. Simply, blarcamesine as a treatment for Fragile X needs now to be properly tested in a clinical trial in real humans; beyond the transgenic rodents mentioned in the letter.

Once again, it’s the “mice aren’t men” thing. Blarcamesine naysayers will claim that it can have no viability as a treatment for Fragile X in humans until a proper clinical trial proves it. Fair enough. I’ll be holding (and perhaps increasing) my AVXL position. No reason whatsoever that humans with Fragile X won’t benefit as did the lab rodents. I’m entirely confident that the mouse models of Fragile X predicted how the drug will work in humans.

Nope. Not likely.

Well, the factual assessment data continue to accumulate, which coupled with the abject failure of all of the amyloid treatments for the last two or three decades should seal the deal.

But, it won’t. Dozens of researchers and drug company managers have bought into and spent their entire careers parked on the amyloid etiology thesis. To turn away from it will be to admit professional error, reflecting scientific incompetence. These people spent years and tens of thousands of dollars getting their MD or PhD degrees. No other group knows what they know; they must be listened to. They possess the accepted, respected knowledge on what, certainly, must cause Alzheimer’s. Their research has appeared in all of the major medical research journals, with peer and editorial reviews.

So, no, I don’t expect any turn-away from the amyloid hypothesis until blarcamesine has been on the market for several years and, finally, millions with Alzheimer’s finally gain relief.

In the medical history books, it will be an additional chapter, showing how, of all professions, medicine most adheres to “accepted knowledge,” resisting utterly new perspectives and therapeutic approaches. It took a half-century to get the germ theory accepted as the cause of disease; the reigning medical poobahs had to first die off. It was known that diseases are caused by the unhealthful re-breathing of stale air at night. Pasteur and Lister were on-the-edge medical weirdos, with goofy ideas. Like Missling, et al.

New Evidence for Blarcamesine-induced Autophagy for Alzheimer’s

Evidence mounts. Alzheimer’s is not caused by “amyloid buildup outside of brain cells.” A new paper finds that in Alzheimer’s, lysosomes, filled with acidic enzymes involved in the routine breakdown, removal, and recycling of metabolic waste from everyday cell reactions, are dysfunctional.
https://www.eurekalert.org/news-releases/954383

This particular autophagy, removal of wastes inside cells, is compromised, which allows the accumulation of toxic wastes inside the cells, thereby disrupting normal cell functions. In brain cells, Alzheimer’s results.

Here are the definitive statements:

“...future treatments should focus on reversing the lysosomal dysfunction....”

Really? That’s exactly what blarcamesine facilitates: healthful, normalized autophagy, cellular waste clearing, accomplished by properly-functioning lysosomes.

Download or use an installed spreadsheet program.

For those without a spreadsheet program on their computer, do a web search for “online spreadsheet programs.” Or, see if Excel is already on your computer (or some other spreadsheet).

Then open it; take some time to learn how to do simple arithmetic on the spreadsheet. Collect and enter the data. Here’s how to do it: https://www.lifewire.com/excel-step-by-step-basic-tutorial-3123501

You can start with the list of diseases and conditions listed in the Anavex pipeline. Put each of those in column A. At the bottom, enter the names of any other potential diseases or conditions.

In columns 2 and to the right, enter what you find to be useful info. Number of patients in the US, then in Europe, etc.

Lots of info on page 12, to start with, here: https://www.anavex.com/_files/ugd/79bcf7_02b343eb47da4dfcb7e099f378b3b5f4.pdf

I don’t see any way that I could attach my Excel spreadsheet for Anavex. Even if I could, I wouldn’t post it; far to controversial; numbers “way too high.” “Unsupported conjectures; speculation, even.”

I would suggest that those unable to use a spreadsheet to calculate potential Anavex investment metrics should confine themselves to only currently published Anavex data. If one is unable to do all of the involved arithmetic, any conjectural numbers will be suspect, high or low.

How many, and which diseases? How many will be treated for each? How much will Anavex sell a year’s treatment for each patient. What, then, will be annual revenues for each disease? What percent of those revenues will drop down to be distributed as per-share dividends? With any of the calculated dividends, what would be the range of resulting share prices (the P/E ratio)?

For all of these, count the potential highs and lows, to see the range of possibilities. My calculations indicate that Anavex needs to get approved for just one rare disease to be profitable. If it’s for either of the two biggies, Parkinson’s or Alzheimer’s, lots of digits required; have to widen the revenue and total values columns to show them.

Quick bucks? Or long term investment?

Understood. Two differing, contrasting viewpoints on taking or holding an AVXL position.

One is that the share price should or needs to continually advance. If it doesn't, as in the case of the last year, where the price has declined from an intraday high of $31.50 last June, a holding of AVXL shares has been a failure.

The other viewpoint is that getting drugs like blarcamesine approved and on the market takes years, literally. The intervening share price wanderings are accepted and understood. They allow diligent investors to increase their holdings by buying shares during low-price intervals.

Quick-buck investing? Or, long-term investing? Two entirely different approaches; mutually exclusive. For quick-buckers, AVXL is not a play. It will be, however, right after the FDA approves it.

This is a new biotech stock. No guarantees.

Very good question.

First, it doesn’t take an advanced degree to accurately proclaim that “there is not even any guarantee that we are powered enough for approval in AD.” The power that gets blarcamesine approved by the FDA (or other regulatory agency) for Alzheimer’s disease is only one thing, which neither the doc nor anyone else has yet seen — the top line data from the big, long Phase 3 clinical trial of the drug, which will appear only after the trial is completed and detailed analyses of its findings are compiled. My investments in Anavex Life Sciences Corp (AVXL shares) were never purchased on the belief that there was some pre-existing ‘guarantee of approval.’ Stay real. With Anavex we are dealing a new, start-up drug company working on entirely new drugs, with heretofore unknown mechanisms of action, against the most recalcitrant central nervous system diseases. On the face of it, pretty risky stuff, with no “guarantees.”

So, indeed, how can “any of that” translate to a higher share price? Again, only one way; by having the clinical results reveal (with statistically significant findings) that the drug is both safe and yields useful therapeutic improvements over any of the existing drugs for the tested disease (in this case, Alzheimer’s). I, as have others, have checked the info on the existing Alzheimer’s drugs (https://www.alz.org/alzheimers-dementia/treatments/medications-for-memory). When considering the preclinical murine (lab rodent) and early human trials (Phase 1), blarcamesine yields very positive outcomes.

Then, of course, is blarcamesine’s unique mechanism of action (MOA). It is not a cholinesterase inhibitor. It works very differently from Donepezil (Aricept®), Rivastigmine (Exelon®), or Galantamine (Razadyne®), the most commonly prescribed drugs for Alzheimer’s. At best, those drugs merely slow, for a time (not always long) the otherwise lethal progression of the disease. That’s not what happened with blarcamesine in transgenic rats with human Alzheimer’s disease genes or symptoms.

But, of course, mice (or rats) are not men (people). Real double-blind clinical trails, with statistically significant results data will be needed. The speculations of medical professionals (the doc) or former high school biology teachers (me) will play no part in the FDA’s decision on blarcamesine — thankfully. Only stat-sig clinical data will count. Those will appear sometime in the future. Until then, we are all speculating.

Of course, those harboring any anxiety about blarcamesine’s future ought to just sit back and be entertained by the postings on this board, good and bad. Keep stock investment dollars safe, in a proven mutual fund, CD, government bond, or cash.

Or, with discretionary funds, take a small AVXL position. By the end of 2023, all of the questions previously posed will have answers.

Punch it out on a spreadsheet.

Calculate both the high and low possibilities.

I’ve created a detailed spreadsheet into which I’ve added various ranges of potential Anavex data. One column has a lengthy list of potential diseases and conditions any of the Anavex drugs may eventually treat (or prevent). In the next range of columns the numbers of cases of each disease in various countries and regions of the world. Then, in the next columns potential annual revenues from each of the numerous patients. In the last columns, arithmetic products when the appropriate cells have been multiplied. In the next to last column, resultant AVXL share price calculations. In the last column, the resultant value if my AVXL position for each disease or condition.

I’ve tried to rank the diseases by probability of sales approval, from the ones yielding the lowest annual revenues (such as Rett) on down to those with the biggest annual revenues (prophylactic and anti-aging applications).

In all cases, to get a picture of the ranges of possibilities, I’ve got lowest-possible numbers on up to highest-possible numbers (where such a range could be possible).

Of course, the far-right column calculates the worth of my modest AVXL position for each disease, condition, and application. At the lowest right is the sum-total value.

For those not moderately skilled in spreadsheet creation, none of this has value. But all calculations are elementary arithmetic. Cell A-1 times cell B-1, etc.

And, yes, my spreadsheet lays out numbers in the range of those just posted by JWC3. Far too big to quote here; not believable. I have only a few thousand shares of AVXL, purchased over the years (at an average base price of $2.91), knowing full well that sooner or later Anavex Life Sciences Corp could go bust; that I could lose my entire investment in the company. Diligently, I’ve used only fractions of the discretionary dollars in my budget. If Anavex goes bust, my life is unchanged.

If blarcamesine gets approved for just one or two diseases, the beneficiaries of my estate will be well rewarded. If most or all of the listed diseases and conditions get approved, my estate will have generational wealth, much of which will go to appropriate philanthropies.