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Yea, potential hypertensive therapy, too.
Don't forget the initial 10 off of Systolic blood pressure. I belive we have the patients now to figure out if that is a happening!
Or, before.
By prompt, I am assuming you mean after a positive readout from the planned P3 PDD trial perhaps some time in 2023?
Very likely.
Does this [ciprofloxacin impairment of mitochondrial function] describe a process that could create the failure?
Will have to wait.
Since you are in speculation mode what are you expecting from the upcoming peer reviewed article?
Consider aspirin's history.
TGD's aspirin comment keeps ringing in my head.
Far out speculation. But....!
how many other neuro developmental diseases may be included
in this mold? The genes are within the code, but not properly expressed by chromatin?
Here, I just recall what I taught.
falconer, another outstanding piece of explaining this disease. We are so glad and blessed that you found this MB.
By chance, do you have a photographic memory?
Blarcamesine facilitation of chromatin function probably favorable.
Any thoughts on the undisclosed rare disease in our pipeline? [Fragile X Syndrome]
Actually, no there isn't.
There's a first time for everything.
Exact, precise summary of Missling's presentation.
MayoMobile, thank you for presenting this very accurate listing of Christopher Missling's presentation points. It is worth considering each of these listed points of fact; they indicate where Anavex Life Sciences Corp is headed.
I listened intently to Missling's discussion. His laying out of the Anavex science comported exactly with what I knew about it. It is strong, wide, deep, new, and innovative.
Like others, I was delighted to learn more of the details where and how the various trials will proceed.
Most important were the clinical trial data he presented. Of course, they are not yet complete, but in every case they point to extremely strong clinical readouts later in the year. Solid, through and through.
Since I took my first small AVXL position about five years ago I've continued to scrutinize all of the Anavex science that I could find. Back then, most of it derived from murine (lab rodent) studies; which I carefully projected on up to humans. That's not always a wise or accurate thing to do. Mice aren't men, at least in many respects.
But as a biologist familiar with cytology and cellular biochemistry I could see that the Anavex sigma-1 receptor activation in lab rodents with transgenic human diseases, yielding propitious therapeutic resolutions, would happen later in humans, too. Everything Missling indicated confirmed that informed conjecture. Anavex science at work in humans, with a wide diversity of diseases and conditions, is no longer anyone's conjecture. The trials' readouts later in the year will thoroughly squelch whatever Anavex naysaying that might yet persist.
The next two or three years are going to be very exciting, for both those who hold AVXL positions, and for the multitude of people who will be successfully treated with the Anavex sigma-1 receptor activators.
Nope. Other way around.
Doesnt mRNA communicate with a Cell's dna to make changes?
Am unaware of such a molecule.
Can be of no help.
Lots of zeros, of great value.
If Anavex can eventually gain $300,000,000,000 (three hundred billion dollars) of annual revenues for the treatment of Alzheimer's globally, with about 67 million AVXL shares (the current number), the income, per share ($300,000,000,000 / 67,000,000) would be $4,477.
How much of that might drop down as a per share dividend? At 1%, $44.77. At 5%, $223. If 10% were distributed as a per share dividend, shareholders would receive $447 for each share.
Do your own arithmetic for larger drop down percentages.
Then, using whatever price to earnings ratio (P/E) you'd like, or what other appropriate method, calculate potential share prices.
Of course, these calculations deal solely with Alzheimer's disease. Which other diseases and treatments might also bring revenues to the company? Parkinson's will be giant, of course.
Of the greatest value would be near-universal use of an Anavex drug as a general prophylactic, to prevent a diversity of diseases and conditions, far beyond those presently being investigated.
Anavex derangement syndrome.
An untreatable disorder.
Dr.M. is basically telling us AVXL either already have (or soon will) have evidence they have validated and verified the AVXL MOA claims for (regen/restore) CNS cellular homeostasis....
The shared Lewy body problem.
The linked article in the referenced posting tells how Lewy bodies, "abnormal proteins," are linked to both Parkinson's disease and Alzheimer's disease. It tells of some genes that may be involved with Lewy bodies.
Well and good. But what is never discussed in any useful manner (because conventional perspectives of these diseases are incomplete) is just why, in most cases, the diseases have a geriatric onset. Twenty-five year-olds have little to worry about. Sixty-five year-olds do.
Doubtless, the various genes discussed in the article are important. If they are present, any of the discussed CNS diseases are very likely in older years. But, here's really big question, neither asked nor answered.
What kept those pathogenic genes from becoming expressed early in life? They were in the genome, but something prevented their expression. But, later in life, something allowed the genes to be expressed, to operate. It's inadequate to claim, "Yea, sure, it's just normal aging." Convenient, but simplistic; failing to describe a mechanism.
Might Anavex, however, provide an induced mechanism that would prevent, even in age, the operation of those pathogenic genes? Perhaps, might blarcamesine's modulation of chromatin --- which is intimately involved in gene expression --- prevent geriatric expression of these and other similar genes?
Again, none of these people with the bad genes had any of the diseases in youth, even for the most part into middle age. Then...for unknown reasons related to aging, they were activated. Was that geriatric activation caused by reduced production of properly-folded enzymes (specific proteins)? Or, by chromatin disfunctions also caused by aberrant proteins --- both of which blarcamesine could have rectified?
Of course, as in most other similar papers, the "blame" for the described CNS diseases is laid upon the Lewy bodies themselves; implying, of course, that some drug that could remove them would be efficacious.
Not with Anavex, however. That company's drugs target, treat not the downstream waste proteins, but, rather the actual upstream chemical dysfunctions that first fail to prevent the protein wastes. Fixing things at the biochemical start. Far better; and more effective.
I'll get paid.
...thank you for an excellent , easy to read, factual, response. We do not pay you enough.
The liver doesn't like the molecule
The new Alzheimer's drug, of this other company (not Anavex), targets some toxins produced by a bacterium that causes gingivitis, gum disease. The bacterium is found in most people who have Alzheimer's, and the company proposes that the toxins it produces also cause Alzheimer's. Stop the toxin, stop the Alzheimer's.
In the clinical trial of the new drug, "...hepatic adverse events..." have been detected. That means that the liver is responding adversely, having side effects there.
The liver, of course, is the main chemical processing center in the body, grabbing and dissembling any and all toxins coursing through the blood stream. But, some toxins stress the liver; apparently what's happening with this drug. Wisely, the FDA is halting or postponing the clinical study.
They may find that the liver learns to accommodate itself and after a period returns to normal function. If so, the study can be resumed, with close monitoring of hepatic (liver) function.
It should be noted that none of the Anavex drugs have ever evoked hepatic adverse events. They, simply, are not toxic.
Once, again.
No. These are theories and postulates.
Thanks for the links regarding Anavex; chromatin.
This abstract excerpt from your link provides the appropriate focus:
Epigenetic mechanisms are fundamental key features of developing cells connecting developmental regulatory factors to chromatin modification.
The Anavex chromatin factor to be demonstrated.
The rather recent contention that the Anavex sigma-1 receptor agonists can not only favorably modulate protein folding, thereby treating or preventing a number of central nervous system diseases, but also modulate proper chromatin functioning in genetic expression is immense. Genetic expression is the working of genes, the DNA segments, to ultimately cause biochemical outcomes. It's a complicated process, open to all sorts of problems. Genetic expression must be perfect, or very untoward things happen. Genetic diseases. Chromatin has to precisely operate in the process.
Presently, I can find no actual studies demonstrating that any of the Anavex sigma-1 receptors accomplishing this. I don't, however, question the matter. It will be very interesting to see such information emerge. I'm familiar with how the Anavex molecules can be used, tested for anti-aging outcomes, in various test species (such as the roundworm Ceanorhabditis elegans). But for chromatin studies, any number of organisms, from unicellular protozoans on up to various invertebrates might be test subjects.
Anyone know which organisms might be used to both test and demonstrate this phenomenon? Better, are there any existing chromatin studies involving the Anavex molecules?
If oral administration of blarcamesine, or Anavex 3-71 (at its far more minute dosage concentrations) might comprehensively direct precise gene expression, the applications will be far greater than anything currently envisioned.
Dosing might begin prenatally, before birth, to prevent genetic diseases that result from anomalous gene expression. Rett syndrome might be one of those. There could be hundreds more. All sorts of epigenetic applications.
There very likely would be gigantic applications in animal husbandry, promoting full and favorable gene expression in farm animals.
I'd also like to learn if blarcamesine or Anavex 3-71 (the later, in particular) might, in its low concentrations, facilitate precise genetic transfer in meiosis, the production of functioning, haploid eggs and sperm cells. Could Anavex 3-71 facilitate accurate transfer of genes from the parent on into his or her gametes (sperms and eggs) so as to reduce or prevent genetic errors?
Anavex, please, get some molecular biology grad students to investigate all of this, to get some preliminary indications of applications. If any are positive, the eventual Anavex story will be even larger, significantly changing medicine and human (and animal?) health in the future.
It seems that we are with the Anavex chromatin factor about where we were with the exact mechanism of action (MOA) of blarcamesine five or six years ago — back then very hazy. No longer. May the Anavex chromatin MOA soon come to clarity.
For we biologists, all so exciting. Profound new stuff. None of it in the textbooks yet. Someday....
When Anavex 3-71 enters the stage.
There has been some speculation(no I can't prove it) that 3-71 might be a more potent version of 2-73.
Disregard these calculations.
Below, I've hypothesized some potential annual sales revenues, should blarcamesine someday be approved for generalized use as an anti-aging prophylactic, a mini-aspirin, as it were (as Dr. Missling alluded to in the conference call).
First, should any of this work out, come to medical practice, the revenue streams to Anavex Life Sciences Corp are many years on out. Not the kind of thing that should guide the taking of an AVXL ownership position right now. There are lots of more relevant and controlling other data on that presently available for intelligent investments in AVXL equity positions. Nonetheless, ponder the numbers I post below.
The first presumption in my metrics is that blarcamesine will prove to be both utterly safe (like aspirin) and very successful in preventing or slowing the geriatric (older-age) onset of a diversity of diseases and conditions. Therefore, the drug (in this hypothetical scenario) will be universally prescribed to everyone at the age of 50, to be taken continually (without interruption) each day. With that, the health of people aging past 50 greatly and sustainably improves.
Let's confine the numbers to just the U.S. Global sales can be calculated later.
Let's presume (very conservatively) that the U.S. population will be 300 million. Then, with a convenient off-hand determination (probably incorrect) I'll presume that one-third of those, 100 million, will be 50 years or older; and would be taking a dose of blarcamesine each day.
How much, then, would a daily dose of prophylactic blarcamesine cost, either by the patients themselves, or their health insurance companies? Who knows? But let's be very conservative, and presume it will be a bit over dollar a day coming to Anavex Life Sciences, averaging out to a per patient annual cost of $500. That's $1.37 a day for each dose.
Next, I'll presume that fabrication and distribution costs are, conveniently, $0.37 per day per dose. That's a dollar a day from each of the 100 million blarcamesine users in the U.S. as profit margin.
100,000,000 users x 365 days x $1.00 profit margin gives a total continuing annual income to Anavex Life Sciences of $36.5 billion dollars.
If the company had 100 million shares in circulation (66.96 million shares presently are in issue), that would be $365 of cleared sales revenue for each AVXL share. Use your own Price to Earnings Ratio to calculate, then, a probable AVXL share price.
Of course, these revenue numbers may be off by a half or a quarter, two to four times larger.
Then, try to plug in global sales. Multiples of any of the above.
Blarcamesine, a new 21st-century aspirin? Let's see. Very possible.
No more need be said.
100% of patients continued in the extension study. Reason - "interest from participating patients and family"
No, he knows.
I just loved the aspirin comment.... He believes!
Missling mentioned eventual prophylaxis.
For the Anavex phone conference, I listened closely, trying to discover where my own understandings of Anavex drug biology failed to match what Dr. Missling discussed. Very pleased. Everything he mentioned aligned with my own perceptions and understandings. Seemed that he was reading from notes I would have assembled for such an event (which was also the case with the comments of Dr. Randi Hagerman and her comments on blarcamesine not long ago).
In honesty, I do not follow closely the on-going details of the several Anavex clinical trials, either in progress, or to come. I'm only interested in their final read-outs, and Dr. Missling mentioned that some of those will appear later this year. Well and good.
I would have loved to hear one of the questioners ask if any information on animal studies regarding blarcamesine's suppression of aging and geriatric disease onset have been conducted. Inasmuch as this event was for stock analysts, no such question was posed, But I did note that Dr. Missling, for the first time, I believe, posed a potential prophylactic application of blarcamesine, suggesting that some time in the future the drug might be an "aspirin," taken daily for its health benefits; disease prophylaxis, actual prevention.
I've been contending that for sometime; where blarcamesine's greatest health benefits and impacts are likely with its prophylactic uses, taken, as Missling alluded, to actually prevent the onset of geriatric diseases. Not just to treat Alzheimer's, but to actually prevent it.
Should that happen, ponder the implications, both for citizens' mental health, and for the sales revenues coming to Anavex Life Sciences Corp.
I'll be maintaining my long-term, five-year investment periods perspective regarding AVXL. The first five-year corporate development and start-up period is coming to an end. The next fire-year period will be with ever-increasing sales revenues. The five-year investment period after that will have Anavex Life Sciences Corp at the top of the world's pharmaceuticals, with all that will entail.
Thanks, my error.
"There is many of those, not just Alzheimer's."
Expanded therapeutic significance, application of blarcamesine.
This bulleted paragraph In this morning's Anavex media announcement is extremely important; revealing a new, broader therapeutic significance of blarcamesine:
Researchers at the University of California San Diego have identified the underlying cause of Alzheimer's disease in neurons. They discovered that changes in the structure of chromatin are responsible. [2] Sigma-1 Receptor (SIGMAR1), the direct target which gets activated with ANAVEX®2-73 demonstrated to restore chromatin structures. [3]
Blarcamesine for amyloidosis.
First, you've nicely presented the question. (A- grade.)
Whether or not blarcamesine might be able to treat or prevent this rare but very serious disease is unknown. But, very clearly, it needs to be investigated. Ideally, there are murine (rat or mouse) models of the disease, where the rodents, too, accumulate the amyloid proteins.
The real focus should not be on the amyloid deposits themselves, but rather on the anomalous mechanisms that cause them. Fix the cause, the etiology, not just the symptoms, the protein accumulations themselves. That, of course, is where blarcamesine differs from the several, now-failed immunotherapies for Alzheimer's disease.
So, could blarcamesine do this; prevent the depositing or accumulating of the amyloid protein? Very possible, particularly if it is caused by a misfolded enzyme that controls, destroys, or removes amyloid proteins before they accumulate. This would be part of the cell's normal homeostasis. Blarcamesine has diverse homeostatic support and restoration abilities. Let's get it into transgenic rodents with amyloidosis and see what happens (if there are such animals). If not, then simply try it in closely monitored human trials.
Well, they are. BUT....
Should Cassava get their new Alzheimer's drug approved, they will be a competitor of Anavex.
But prophylactic use of blarcamesine in future.
Thank you. I didn't use the word "huge" to describe the eventual results of blarcamesine for disease and aging prophylaxis. Many, even so, I'm certain, were turned away from what I wrote. Understood. I'm looking way beyond the near horizon of potential Anavex therapies. To be diligent and conservative, at least in regard to the increasing of an AVXL position, the smart people here know that my projections out on to the long-term Anavex horizon will need scientific substantiation. Right, now, what I stated was only conjecture.
Nonetheless, I'm confident that, in time, Anavex prophylaxis will become a standard medical treatment. Two factors at play on this.
First, I'm certain that privately, unannounced to the public, Anavex Life Sciences Corp has, already in hand, substantial information on the efficacy of blarcamesine as a safe, effective prophylactic agent for any number of diseases or conditions, including generalized aging. As I've noted, biology and medicine has any number of recognized methods and protocols to study the effects of drugs on aging. The simplest, and well-recognized (and not hard to conduct in short periods of time) are aging studies on the tiny lab roundworm Caenhorabditis elegans. There are no reasons Anavex hasn't run aging tests with this organism. Any biology grad student, in a few months, could quantify the antiaging effects. Then, run the tests with lab mice.
The second substantiating factor will spontaneously present itself, after hundreds of people start taking blarcamesine for any of the approved indications. Then, after months or years of such dosing it will be noticed that various indications of aging or other diseases have been suppressed by the drug. When that is discovered, think there might be pressures brought to allow generalized prophylactic use (similar to the statements of Dr. Randi Hagerman, stating she'd like to take the drug for it's good benefits; prophylaxis, as it were)?
But Dr. Missling and his associates almost certainly have data in hand; know that blarcamesine will, indeed have profound prophylactic applications. But they are smart; playing the drug development game carefully and cleverly. It would serve no good purpose to come out, now, and proclaim this new application for any of the Anavex drugs. Wait until the company can sell blarcamesine for at least one disease, probably first for Rett syndrome. That will substantiate the validity of the drug, making it harder to discount the data supporting the prophylaxis of aging and many other diseases.
The next two or three years are going to be very interesting, for Anavex shareholders, and for patients who will benefit from the company's new drugs, with their expanded numbers of applications.
This is Chapter 2.
Hope Falconer can continue to show us how much we do not (yet) know along these lines.
Anavex discussion topics, here, now different.
There is a definite shift in the thinking
Remains to be seen.
Might there be any "reversal of aging" effect or with an older person would typical aging just slow?
How blarcamesine treats Rett syndrome.
Can you elaborate as it relates to Rett Syndrome, since it is a genetic disease? Or, is it more or less related to your last response?
Ok? Ready? An anti-aging agent.
Cancer arises as aging organisms accumulate mistakes (mutations) in DNA transcription that are not then addressed by autophagy. Sounds like 2-73 could help at either end of that equation.
Good Question
...are you saying/implying that faulty genes within an individual can or "may be" fixed by A2-73 due to the process?
Wow. Even bigger, more important. Transcription.
...we propose that Sig-1R [the sigma-1 receptor protein, the one that blarcamesine activates] is a pluripotent modulator with resultant multiple functional manifestations in living systems.
Watching the AVXL price swings.
As an investor in Anavex Life Sciences Corp (AVXL), not a day-trader, options player, momentum player, or short-term player of any sort, I watched variations of the AVXL share price during the normal trading hours today. Shot way up, then settled back down a bit, but for the day, up 41.81%.
Day-traders and short-term players may have sold above the closing price; made some very nice profits today. Congratulations.
But ever greater numbers of AVXL equity holders are taking a much longer, real-investment perspective, merely watching these day-to-day price swings (now, mostly upward). Speaking for myself, I'm making very little of these new, high prices. As a biologist, I know the biology of blarcamesine, and how, once it's approved for just the first central nervous system (CNS) disease, Rett syndrome, everything changes.
So far, there is no regulatory or broad medical professional recognition that blarcamesine can actually be a successful therapy for CNS diseases. For Alzheimer's, the new SAVA results notwithstanding, the problem continues to be, legitimately, the accumulation of waste proteins in nerves, both beta-amyloids and tau tangles. But along with that understanding of that cause of Alzheimer's symptoms, the only plausible solution is some sort of drug that will remove those wastes, after they form. Of course, after spending billions of dollars to create such drugs, all of those immunotherapies have failed.
Later this year, or some time next, when blarcamesine is authorized for sale and treatment of Rett syndrome, everything will change. It's starting to now, with the announcement of some very moderate symptomatic Alzheimer's improvements with Cassava Sciences's new drug. It does not work to remove protein wastes. It apparently re-configures a protein that can help prevent the formation of those waste proteins. Well and good; so much different, and better, than the immunotherapies trying to remove the accumulated wastes.
So, slowly, the Alzheimer's therapy story is changing. The immunotherapies have all failed, often with significant side effects. Not the case with either the Cassava Sciences drug nor Anavex's blarcamesine.
For long-term Anavex shareholders (investors) the key is this. Simply, blarcamesine is the far better therapy. Virtually no side effects, but not only does it fix the bent out of shape molecule the Cassava drug does, it fixes or prevents a multitude of other neuron pathologies. It will win, easily, soon. The blarcamesine biology is altogether favorable. But, understandably, most in the investment world, retail or institutional, won't buy into that notion until the FDA does; after the on-going clinical trials of blarcamesine come to a successful close. Then, any of the recent AVXL share prices will appear inordinately low.
Everyone will be watching Anavex in the coming days and weeks. I'll be watching it for the coming years. Sometime in 2023, the share price is likely to level out, requiring three digits before the decimal. In the meantime, depending on your time frame, everyone, have fun watching.
I started posting messages here a good number of years ago, telling of the unique biology of the Anavex sigma-1 receptor protein activators. Back then, the seminal role of the sigma-1 receptor protein was utterly discounted. The MOA (mechanism of action) of the Anavex molecules was was utterly dismissed. There is no such mechanism it was proclaimed. Today, we don't see any such proclamations. Presently, the only nay-saying exclamations are that "there are no Phase 3 double-blind clinical results yet." True. Those will appear soon enough. And as all of the early human trials have shown, the results of those will be both safe and efficacious. Billions of dollars of blarcamesine sales will ensue.
I'm grinning...with everyone else here
Looks like a number of interested parties, whether retail or institutional, read with interest and understanding some of the postings I put a few days ago, telling (again) some of the unique, powerful Anavex science story lines. But, those are not just a story. Reality
Which fits, now, with the SAVA stuff. But, a close read and understanding of both mechanisms of action (MOAs) show that blarcamesine is much better, has multiple applications and therapeutic outcomes, compared to competitor's drug.
SAVA entered, is in the game, now (with their clinical results). AVXL, however, is the far stronger player; will rack up lots of points; will win the game --- perhaps on a TKO (technical, meaning real technology that works, knockout).
Great Question! (Two extra-credit points!)
...these drugs might be complimentary.