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AAIC Clinical Trials and New Alzheimer’s Drugs Report
An article on the 2017 Alzheimer’ Association International Conference (AAIC) in London states, “Twenty-seven Alzheimer's drugs in Phase III clinical trials and eight drugs in Phase II clinical trials may launch in the next five years,....”
https://www.eurekalert.org/pub_releases/2017-07/apa-2pi071417.php
Note these comments:
There are currently 23 drugs in Phase II and III trials targeting amyloid protein buildup in the brain, while 28 drugs are targeting neurotransmitter activity.
A novel treatment for Alzheimer's hasn't received FDA approval since 2003 and regulatory approval in Europe since 2002.
Sales Price Will Not Result from Production Cost
This is a big question. After FDA approval for any of the several central nervous system diseases Anavex 2-73 will treat, how much will Anavex Life Sciences Corp. charge for a daily dosing? Will that price reflect in any significant way the cost of the dose’s manufacture?
If that’s the major fraction of the drug’s sales price, it will be very low. With the greatest dose concentration of, say, 50mg, that’s 20 doses per gram, or 20,000 per kilogram. If it were to cost, say, $400 to make a kilogram of Anavex 2-73, each dose would cost $0.02.
At ten times that, a dose would be $0.20. And for some conditions, optimal dosing may be less than 50mg.
No drug is sold solely at manufacturing cost. Anavex will want to recover, over time, at least, testing costs, marketing (drug representatives going into doctors’ offices to explain the drug), etc.
No way to know with any accuracy the eventual sales price of Anavex drugs. Will be interesting to see how the company elects to price their products.
Interesting Ethnocultural Health Study, re Alzheimer’s
The NYT article tells of a researcher living with (and in) a tropical aboriginal ethnic group in a deep wild area in South America. He’s studying (among other things) the reduced occurrence of Alzheimer’s in this group of people. They have relatively high rates of infant mortality, but compared to Western populations elevated rates of aged people in good physical and mental health.
He correlates this to the putative incidence of tropical parasites in the population, where the parasites keep certain gene expressions from causing astrocytes, nerve-nourishing cells, from turning on nerves. With the presence of parasites, the astrocytes are focused on suppression of the parasite infestation, not inadvertently against functioning nerves.
I derived two points from the article.
First, should the researcher’s thesis be proven (not sure just how that could happen; will be no double-blind clinical studies with these people in this remote area), I don’t see how any Western population could or would be infected with a parasite for Alzheimer’s prophylaxis. The parasite, a worm or microbe, might, indeed, reduce or prevent the onset of Alzheimer’s. But the other health-deprecating effects of a parasite could be as bad as Alzheimer’s itself. The legal and ethical problems with the administration of an Alzheimer’s-preventing parasite seem overwhelming. I can’t see it as a solution in any realistic way.
The second, unrelated point I took from the article is this (I knew a bit about this before, further described in the article). Very important for the Anavex story.
A good number of elderly people, in normal mental health (without any Alzheimer’s symptoms), actually have brain concentrations of beta-amyloids and tau tangles equivalent to those with Alzheimer’s. Neurologists continue to ponder just why these folks had no Alzheimer’s, but had giant waste protein accumulations that are so closely correlated to Alzheimer’s.
The key point is this. Some people have normal brains and full cognition even with high concentrations of the waste proteins otherwise thought to cause Alzheimer’s dementia. What could that mean?
Waste protein accumulations are not the sole cause of the dementia of Alzheimer’s; there must be at least one other factor. Might that be (here it comes) neuron dyshomeostasis resulting from mitochondrial/endoplasmic reticular dysfunction, the exact thing Anavex 2-73 corrects?
Virtually all central nervous system diseases are recognized to be a result of or closely associated with mitochondrial dysfunction. The Anavex 2-73 sigma-1 agonist (among other good things) reconnects mitochondria and endoplasmic reticula, restoring proper, healthful, normal neuron function (homeostasis).
With this, the neuron can once again produce properly-folded, fully functioning enzymes, which control virtually all cell chemistry. It is apparent, then, that the enzymes to remove protein waste accumulations are not the only ones to facilitate healthful neuron and nerve function. There must be others, that allow normal synapse function, allowing normal nerve function — no dementia.
I’ve contended all along that the main reason Anavex 2-73 so wonderfully stabilizes or improves Alzheimer’s symptom profiles is because the drug’s restoration of neuron homeostasis allows production of waste-clearing enzymes.
Well, it might be something different or more. Now (with this new knowledge) there is the possibility that after Anavex 2-73 gives Alzheimer’s relief, the patients may still retain high concentrations of the waste proteins, but now without the symptoms they putatively always cause (well, not always, as noted in this article).
In short, Anavex 2-73 may suppress dementia by some mechanism other than the normalized facilitation of protein waste removal.
This might also be a hint (but unknown mechanism) why the drug and its analogues work against other CNS diseases not complicated or caused by beta-amyloid or tau protein wastes. Something bigger and better may be happening, more than waste protein clearing.
Anavex 2-73 may promote healthful astrocyte functioning, keeping these cells from attacking neurons or nerves.
Would like to learn of this. Link?
(NYT Alzheimer's article.)
I Will Continue to Post, But Not Respond
As a retired biology teacher, it is my delight to explain the biology of the Anavex molecules. I will continue to do so. I will not, however, respond to murky, lame, nebulous, or un-referenced questionings of my postings.
The following comes to mind.
The Race is about to begin. Three Anavex horses are being nudged into the starting gate, one racing against Rett Syndrome, another against Parkinson’s, and the final against Alzheimer’s — the three up-coming Anavex clinical trials.
How might this race go?
As some here have implied, all three will stumble and fall into the dirt, never approaching the finish line. The horses are weak and have no ability to run the distance. Their failures in each lane will be the end of Anavex and this board. Fortunately for those seeing this outcome, they had the good sense never to take an AVXL position. Instead, they kept warning of the impending doom of the company. They saved many from financial losses.
Or, might the race turn out as follows, in any one of these potential winnings.
The gate opens, and off they go. The Rett and Parkinson’s horses cross their finish lines first (they run on a shorter track, just 12 weeks long). The Alzheimer’s horse has to circle the track several times, a one-year trial. But it gets there safely and “wins,” too.
All three of these horses end up in the winner’s circle, and take their prizes, FDA approvals. Anavex is, so to speak, a Triple Crown winner.
And, still out in the lab “pasture” are other Anavex “horses” (molecules) of the same lineage, awaiting their race times. One, Anavex 3-71, in early “training” (lab work on rats) reveals it’s stronger and faster than Anavex 2-73, particularly for Parkinson’s.
Those of us who have taken an AVXL position have placed our bets already. We’re ready for race day. Those who see the Anavex horses as weak and lame won’t be at the track. They will read of results in the Wall Street Journal, or even perhaps on the front page of the New York Times. “New Drug Gives Solid Hope for Alzheimer’s.” “Rett Girls Can Now Be Treated.” “Parkinson’s Disease Can Now Be Fixed.”
And those who watch any of the Triple Crown races watch frequent interviews of the owners and trainers of the horses in the race. The Anavex trainers are world class. The head trainer, Dr. Missling, is top notch. I don’t expect to lose any of the three races. He doesn't enter races his horses can't win.
But after any one of those three wins, I won’t be cashing in my betting ticket for several or many years — if at all. My AVXL shares will stay in my possession while Anavex stud fees (dividends and share prices) continue to escalate.
No More.
As an advanced placement biology teacher, I encouraged students who disagreed with my topic presentations (lectures) and their accuracy to switch to another biology teacher in my high school. If only that could happen here (it can’t).
Henceforth, I’ll not waste any of my time attempting to validate my presentations with additional knowledge resource postings. Those who need to know will learn from the start. Those who are in perpetual, lame confrontation of any and all presented Anavex facts will continue as they have, for their own peculiar purposes (not much related to real biology).
Solid Science is Not An "...overly-positive bias."
Period.
Fact Remains, Sigma-1 Receptors Are the Same
"...you may wish to particularly search for DZP's effects.
Mouse and human cells are endowed with a similar molecular apparatus that regulates differentiation and death. The cells are also similar in the molecular mechanisms by which they execute basic cellular processes. Mice and humans also share organs and systemic physiology and show a certain consistency in disease pathogenesis
Yes, Mice Are Men (Well, Their Molecules Are)
Well said.
If the innate sigma-1 receptors of mice are identical to those in humans and all mammals — which they are — then the actions of Anavex sigma-1 agonists in mice exactly parallel their actions in humans.
Understandably, many have questioned the validity of Anavex murine (rats and mice) tests as indicators of safety and efficacy in humans. Mice are not men — except for their molecular structures and pathways in nerves and neurons. Yes, rat brains don’t have as many neurons as humans, but individually, a rat neuron is very similar to a human brain cell. And in the case of sigma-1 receptors, it’s identical. A proprietary sigma-1 agonist, such as Anavex 2-73, will have exactly the same effects and outcomes in both rat and human nerves and neurons.
It would be a mistake to discount the profound efficacies of the Anavex molecules discovered in tests on lab rats and mice. Those findings are superbly accurate and applicable to humans.
Understand, also, that today, with genetic engineering, the genetic defects of various diseases encoded in the human genome, in the nucleotide sequences of the controlling DNA, can now be inserted into rats and mice. With that, the lab animals have genetically identical diseases or conditions as humans. The testing of candidate drugs for treatment of those conditions in the genetically modified rats will be a very accurate reflection of the drug’s actions in humans with those diseases.
And, unlike in human drug tests, highly variable dosing and dosage levels can be tested. For both safety and efficacy determinations, lab rats can be dosed in ranges from exceedingly small concentrations on up to dosages that kill. With this capability, useful dosage ranges can be clinically predetermined so that humans in clinical trials start off with dosage ranges that were both efficacious and safe back in the lab, in all those white lab rats.
And finally, rat life spans are but a fraction of human life spans. That means that what happens in a mouse or rat in, say six months, happens in a human in a decade or longer. If there are no chronic adverse outcomes in, say, six months of an Anavex-dosed rat, there likely will be none in a human taking the drug for 10 years or so. Rat lives are quick and short. They age much, much faster than we do. But they do age, with virtually all of the indications of human aging. If there are no chronic (long-term) adverse events in Anavex-dosed rats, there should be none in humans.
Announcement of ANAVEX Treatments will be Headline Stuff
Presently, no one of consequence knows of or believes in the developing Anavex story. Just another tiny drug start-up betting it’s murky future on some new, unproven, very-questionable treatment approach.
Ponder, then, what might change later this year when Rett Syndrome little girls’ symptoms get noticeably suppressed (or, better, erased). “New Drug Shows Great Promise in CNS Diseases: Rett Syndrome Test is Successful.”
With that, Anavex 2-73 will have legitimacy. Projections of efficacies against Alzheimer’s, Parkinson’s, etc. will no longer be dismissed. At the first evidence-based hint that patients in the Alzheimer’s Phase 3 study are stable or improving, Anavex then becomes a nationwide public health issue, not an obscure FDA testing or approval question.
“Senator, my mother has Alzheimer’s. How come my doctor can’t prescribe Anavex 2-73 for her?”
With those widespread public sentiments, the corner will have been turned. The game changes dramatically, with the ball and strong players all in the Anavex court. There will be public pressures to get family members and friends on the Anavex drugs. Just exactly what the Cures Act and the new FDA do-it-better imperative mandate.
Frankly, I’m not going to be too excited by any new Anavex announcement before Rett or Alzheimer’s trials data are released. Tomorrow, Anavex could reveal the detailed pharmacokinetics/pharmacodynamics data. Wonderful — but those data will have minimal effects on share prices. Those won’t jump until new masses of retail equity buyers want to get in, and they won’t until something they can understand happens. Successfully treating the genetic symptoms of little girls with Rett Syndrome, or keeping Grandmother out of the care facility will be BIG (dare I say, “Yuge”).
Consider this. Both the new Rett and Parkinson’s trials will be merely 3 months long. During those dosage periods, will there be any way to keep family care givers from disclosing visually discernable improvements of their treated family members?
We may not have to wait for a formal efficacy announcement at the end of those two trials. Care givers themselves may be announcing wonderful results during the trials.
“Mr. Reporter, this is my daughter Esmeralda. She was born with Rett syndrome. She’s been taking this new drug, and my husband I can’t believe how much better she’s been after just two months. We are so grateful.”
“Let me look right into the news camera over there. We went to Uncle Bill’s for a meal yesterday. Just couldn’t believe what we saw. He had no shaking, ate just like the rest of us, and conversed just like he did ten years ago. Uncle Bill has been taking some new drug. It’s fixing his Parkinson’s. So glad to have him back!”
Will a few YouTubes or news reports like these go viral?
I wouldn't; but knowledgeable experts can.
Actually, the Central Nervous System, the brain and spinal nerves, is made of organs (the brain and spinal chord), tissues, cells (neurons and others), and organelles (structures within the cell).
"Homeostasis" is a generalized term, referring to normal function ("homeo-" like, similar, or same; "-stasis: process or condition). The term is generally recognized to refer to the normal processes in the structure being referred to.
Because the chemistry of nerves and neurons is so complex, a multitude of tests are used to discern the process status of the structures being assessed.
This is true "brain science," conducted by brilliant people who have spent years in grad school and research labs.
Fortunately, Anavex has team members with such expertise. They can also contract out investigations that need to be conducted.
More Evidence Anavex-induced Sleep Can Restrict Alzheimer's
Report just out telling how lack of deep sleep for just one night allows the detectable accumulation of the waste beta-amyloid protein in cerebral-spinal fluid. After a week of poor sleep, tau proteins also accumulate.
Accumulations of beta-amyloid and tau waste proteins disrupt neuron function, causing Alzheimer's symptoms.
For this well-known reason, drug companies for 20 or 30 years have been trying to devise drugs that clear these symptom-causing wastes --- utterly to no avail. Failure after expensive failure.
It's the record of those failures, by top-level Pharmaceuticals, headed by world-class PhD researchers, that have so profoundly suppressed Anavex share prices. The bashing critics ignorantly think Anavex 2-73 is but another failure-fated protein waste remover. So little do they know or understand.
Anavex 2-73 has a demonstrated record of allowing deep, healthful sleep in Alzheimer's victims. This might be a factor or reason the Alzheimer's patients in the Australian Anavex study either stayed at baseline symptom levels, or actually improved. Perhaps the sleep induced by Anavex 2-73 allowed, at least to a degree, more normalized cognition facilitated by sleep-induced reduction of the waste proteins.
https://www.sciencenews.org/article/just-one-night-poor-sleep-can-boost-alzheimers-beta-proteins
Would $15 billion be a good buyout price?
I punched the appropriate numbers, and personally I’m very much against some Big Pharmaceutical buying out Anavex for $15 billion. Here’s why.
Ihub states that there are 41,380,000 Anavex shares in circulation. If all of those shares were to be purchased with $15 billion, each Anavex share would turn into $362.40. Pretty nice return of a share that closed today at $5.35. That’s a greater than 67x gain. Who, with a choice, would pass that up?
Were it my decision (it’s certainly not), I’d nix that deal in an instant. Given Anavex’s potential corporate value, $15 billion would be a steal for the buyer, and a cheap give-away by Anavex. For those of us who own AVXL shares, we’d be crying (or seeing if there were grounds for a lawsuit) in several years when a number of Anavex pipeline drugs come to market and treat and prevent a multiplicity of severe diseases.
If Anavex 2-73 were approved for and could be used only for established Alzheimer’s cases, $15 billion might be, perhaps, about half an equitable price.
But Anavex Life Science Corp. has a monstrous amount of solid ice yet below the water (re Missling’s revelatory aside, “Just the tip of the ice burg....”). Worldwide sales of Anavex 2-73, against the expanding global presence of Alzheimer’s (more and more people aging as populations expand) will yield gigantic annual revenues.
Let’s imagine 30 million of aging Americans are prescribed Anavex 2-72, along with, say (very conservative) 30 million more in other Western countries. It would not be unreasonable to presume Anavex would clear (profit, after taxes, all costs) $1,000 per year per Alzheimer’s patient. The US government would be just delighted to fork over, say, $2,000 a year in prescription costs to offset the many tens of thousands of dollars of annual health care costs of Alzheimer’s victims.
So, worldwide each year, that would be 60 million having their health preserved or improved by Anavex, which clears $1,000 from each Anavex 2-73 user. That’s a corporate profit, each year (not just once) of $60 billion.
With those projections (which are very real), what Big Pharmaceutical wouldn’t fork over $15 billion in a minute to buy out Anavex?
Who, among us AVXL longs, would be in favor of such a deal?
Of course, Herr Doctor Missling owns a pretty handsome mound of AVXL shares himself. More than us, he knows their real projected value. I don’t think he’d cut such a bad, quick deal.
And that’s in consideration only of Anavex 2-73 against Alzheimer’s. Very high chance that Anavex 3-71 will be equally useful against Parkinson’s disease, along with amyotrophic lateral sclerosis, and a number of other, less frequent central nervous system diseases.
Added to all of this may be cancer and heart disease therapies or preventions. As I’ve posted before, should Anavex 2-73 prove to be a universal soporific (sleeping pill), that global market is many hundreds of millions or a few billion each year (or more).
“Ok, then, Falconer, what would you sell your AVXLs today for?”
I’ve got a few hundred or so. You can have them at $1500 each.
And in a few years, when value exceeds $2000, I’ll regret the sale, particularly because of my loss of eventual recurring annual dividends. For fun, calculate what those might be yourself. It’s just 7th grade arithmetic.
Inadequate Sleep Emerging as a Major Problem
Drudge just posted this BBC article:
http://www.bbc.com/capital/story/20170707-the-worrying-effects-of-working-more-and-sleeping-less
Anavex 2-73 has shown to allow virtually universal normal sleep in the Australian Alzheimer's clinical trial, in a population known for profound sleep problems.
As noted so many times before, in the Australian clinical trial there were no adverse events (side effects) that would prevent or complicate the use of Anavex 2-73 in humans.
No side effects, and solid sleep. Might there be a giant 21st-century market for a drug with those traits, far beyond just Alzheimer's patients?
Yes, Where Are the PhDs?
Investment banks and proprietary investment shops employs Phd. level analysts with bio/medical backgrounds. I doubt lack of understanding of the science explains the perceived low pss of Anavex.
No Present Corporate Need for Public Announcements
I'm certain Anavex has or could find science writers and webpage generators who could, for retail equity buyers, more completely tell the unique and powerful Anavex story to lay audiences.
But, the reality is this.
Presently, the success of the company depends in no way on current share prices; up, down, or sideways. Anavex Life Sciences Corp. does not make any significant operating funds from the sale of new shares at increased prices.
Instead, the company, more usefully, is focused on assembling and conducting acceptable FDA clinical trials for Rett Syndrome and a much larger and longer affirming double-blind Phase 3 Alzheimer's treatment study. Whether we retail AVXL equity holders like it or not, share prices are, for the company, presently irrelevant. Getting the science confirmed in humans and FDA-approved drug sales are most important.
And, once accomplished, those will elevate share prices faster and steeper than any summertime release of some otherwise weak analytic data unconnected to any future drug approval. Yes, as a biologist I'd love to see whatever pharmacokinetics and pharmacodynamics data the company has. I'm certain they would be very positive; might even hike the share price a buck or two.
But our knowledge of those data would advance corporate progress by no degree whatsoever. Again, Anavex Life Science Corp. is not a share-selling entity. Instead, they will be making monstrous revenues after their drugs get approved. We shareholders will, then, benefit tremendously, by orders of magnitude beyond what any near-term PR announcement might induce. Continuing long-term corporate success is the proper, being-worked-on goal.
AVXL is not appropriate, as the record illustrates, for short-term day traders and momentum traders. It's a long-term play. Presently, for those of us outside the labs and corporate offices, it's as boring and unrewarding as possible. The wait, for sure, is frustrating. But of such is the nature of eventual high success. The nondisclosure of masked data or the non-release of "useful" press releases (properly, "media releases" in this century) is a deliberate corporate consideration. The company, presently, is acting in the long-term interests of shareholders, not attempting short-term measures that might be moderately pleasing, but likewise contaminate private dealings with the FDA or corporate collaborators.
The Street Weighs Things Differently.
I, too, marvel at The Street’s (institutional equity-buying or advising firms) negligence, neglect, or dismissal of the now-clear Anavex science. Just why aren’t institutional buyers taking ever-larger Anavex positions before the equity’s share-price ascent?
With this, I’m stating things way out of my league, way beyond most of my expertise — except for my award-winning biology teaching experience.
The matter, I think, in some great degree, is this. An understanding of molecular biology, even for students (of all ages) destined for or attained in accomplishments in many difficult fields (such as investment finance — equities, etc.) is simply too difficult to confidently understand and apply. No one would expect the high-paid experts at equity-buying firms to understand quantum physics. Likewise, they don’t understand (or study) the arcane molecular biology of nerves and neurons.
Yes, there are a few blokes (me, among the foremost of such) extolling the genuine futures of the Anavex molecules. But no professional equities advisor would — quite understandably — take anything I post into consideration. I’m an unknown, with perhaps dubious motives and presentations.
Simply put, for those unable to pass a biology major’s sophomore neurology molecular biology course final exam, Anavex’s presentation of such science is simply disregarded. Too hard to understand. The Anavex stuff can’t be real.
Gotta see some REAL science, a successful double-blind Phase 3 clinical results database. That will be understood by all.
Biology, Chart-reading, or the Failures of Others?
I lost a bit in an earlier company, which had, likewise, a transformative biotech, but was under-funded and unable to bring its molecules to FDA approval. I had the good sense (did due diligence) to limit my initial position, should the company (as it happened) not be able to synthesize, test, and get approved its unique antibiotic molecules.
Anavex skeptics from the start have boldly (and accurately) proclaimed the exceptionally low success rate of start-up biotechs, conveniently lumping Anavex with them. Seen one, seen ‘em all, is the implication.
This is a particular problem with Anavex, inasmuch as it’s targeting Alzheimer’s disease. Any number of Big Pharmaceuticals have spent billions of dollars on a multitude of drugs aimed at clearing amyloid beta and tau tangle protein wastes in nerves. Not a one of these have been successful.
Therefore, without any useful understanding of molecular biology and neuron cytology, one can necessarily presume that Anavex can be no different. Simply put, after three or more decades of drug trials against Alzheimer’s nothing has ever worked. It’s good thinking and due diligence on the part of retail equity investors, then, to be assured Anavex can be no different. End of game. Time to go on to something else.
My decision in taking (presently) a small Anavex position is NOT based upon chart-reading, nor the multiple failures of other drug companies. I’m a biologist and understand elemental neuron cytology, physiology, and all of the associated molecular biology. With this, it is clear Anavex 2-73 operates in no manner similar to the protein waste-clearing drugs that have all failed.
And, as a biologist, I know (as does FDA) the critical and confirming accuracies of murine studies for pre-clinical testing and characterizations of new drugs. The nerves and cellular chemistry of rats are virtually identical to humans.
Moreover, the specific mechanisms of action of Anavex 2-73, on a molecular and sub-cellular level have been clearly discerned and presented by Anavex scientists (see my earlier posts on this).
And, unlike my previous biotech (which failed), Anavex is strongly funded, able to go forward with the ensuing clinical trials.
I would encourage retail investors to closely examine and consider both due-diligence perspectives:
1. The record of previous drug trials by many companies against Alzheimer’s (all of which have failed).
and/or
2. The scientific determination that the Anavex approach to Alzheimer’s treatment is categorically very different from the previous failures, because of Anavex 2-73's unique, effective, safe mechanisms of action in restoring neuron and nerve homeostasis.
Anavex 3-71 Will Be Big
With upcoming clinical trials of Rett Syndrome and Alzheimer’s, the focus, quite properly, has been on the drug being tested, Anavex 2-73. The Anavex 2-73 data from murine (rat and mouse) experimentation has been thoroughly laid out in technical papers. The human data from the Australian trial, depicted at the CTAD conference presentation, is astounding, showing maintenance or improvement of cognition for mid- to moderate-level Alzheimer’s patients, without disqualifying side effects. Not a scintilla of evidence that this won’t be exhaustively confirmed in the much larger Anavex 2-73 Phase 3 trial to be started later this year.
But the Anavex pipeline is massive. Presently, only Anavex 2-73 has had any human trials. But, as the link in the reference post shoes, Anavex 3-71 may be even more efficacious.
“... although that the transgenic McGill rats had a very late stage of Alzheimer’s disease-like pathology (13 months of age), treatment with ANAVEX 3-71 fully reversed cognitive deficits, reduced amyloid pathology and also significantly reduced inflammation. Furthermore, the sustained recovery in cognition and pathophysiology observed following a month-long washout phase in advanced pathology (19 months of age) strongly suggests true disease-modifying properties of ANAVEX 3-71.”
Strong Sleep as a Restorative Factor
Here's something not yet laid out, but, perhaps, really big.
Until recently, the role and purpose of sleep (in all animals) was a mystery. But recent research has proven conclusively that the purpose, function and necessity of sleep is to allow the clearance of brain, spinal chord, nerve, and neuron wastes.
Could it be that after a period time the normalized sleep induced by Anavex 2-73 brings about the clearing of molecular and ionic wastes in both neurons and nerves, restoring pre-disease conditions? The sleep-induced clearance of the wastes that cause the various central nervous system disease symptoms may be a yet-unrecognized big factor.
We know with certainty that, among other actions, Anavex 2-73 reconnects mitochondria and rough endoplasmic reticula, restoring proper and normal enzyme production in neurons. Those properly-folded enzymes then restore normalized cell and nerve chemistry.
But also the deep and adequate sleep induced by Anavex 2-73 may play a large role in symptom suppression in Alzheimer's disease. This might explain why symptom suppression occurred only toward the later months of the Australian trial. It took several months for the sleep-generated clearing of wastes to be fully effective. It took a while for sleep to clear out cellular junk, allowing neurons to function normally again.
And, yes, induction of strong, consistent, normalized sleep may likewise have a multitude of good outcomes regarding any number of other diseases.
Anavex 2-73. Can you say, "Health-giving anti-aging drug?"
[Check this: https://www.nytimes.com/2017/07/05/well/mind/poor-sleep-tied-to-increased-alzheimers-risk.html Pretty supportive of my hypothesis.]
The Insomnia "Blockbuster."
Insomnia may be the low hanging fruit. But dementia will be the real blockbuster.
Rett Reminder
The condition is Rett Syndrome.
Too often, and quite incorrectly, the disease is misnamed as any one of these:
Rhett Syndrome Should have no "h." "Rhett" is a person's first or last name, unrelated to the disease.
Rhett's Syndrome Two errors. Should have no "h," and the proper name of the disease (unlike some others), is not possessive.
Rett's Syndrome One error. Should have no "'s."
Again, properly, the unfortunate disease is properly and simply just Rett Syndrome, no "h" and no apostrophe-s.
Why Stay?
Inasmuch as AVXL share prices have not ascended with the general ascent of the major stock indices (DOW, NASDQ, etc.) in the last many months, it’s a wonder why anyone seeking daily or weekly share price increases would hold on to an AVXL position.
It should seem obvious by now that Anavex share prices have no chance of ascending beyond the narrow trading range of the last several months until something big and substantive appears (new clinical results, analyses, etc.). And none of that is likely until next fall or winter (or later).
For those of us who know the Anavex molecular and cellular science, and familiar to a useful degree with the lengthy and convoluted protocols required for FDA drug approval and commercial sales, we knew from the beginning of our share purchases that favorable share price increases and profitable maturity could happen only at length, many, many months to several years in the future.
I had been following Anavex for some time before I accumulated sufficient knowledge to support my first small position in May 2016. I knew full well I would not see any useful or rewarding AVXL share prices until 2018, at the earliest. Some, then, would regard my Anavex investment funds as the proverbial “dead money.” With my long-term perspective as an investment, not a trading operation, for me, my putatively dead funds are well-invested.
Clearly, in the first quarters (and perhaps for the entire year) of 2017, AVXL is likely to be a continuing disappointment for those with near-term trading desires, seeking to buy and then flip for some quick profits. I don’t see any of those.
Would any of the short-term traders here now recommend AVXL to other rapid-sequence traders?
Those of us with a long-term investment perspective have done our detailed due diligence, have confidence in the exceptional team of corporate officers, and have developed intelligent anticipation of the eventual approval of, at the start, Anavex 2-73. Later, the several other medically transformative drugs in the Anavex pipeline will move into position. We sleep well each night. Our time will come. We have the foreknowledge and patience to wait.
For those lacking these perspectives, why stay sitting on dead AVXL money? With ascending stock market prices, aren’t there many other far more profitable equities to buy and trade? Why Anavex?
Just Who Were the 60% Negatives?
The delay is really tilting the probability to 60% negative and 40% positive in my view
Dead Money?
I bought my first small slug of AVXL shares on 10 May 2016. On an annual basis, I’ve logged about a 14% on-paper gain. I don’t consider that “dead money.”
Are the chart-watching Technical Analysis traders making 14% per annum? If so, just fine. I applaud such efforts. I would be satisfied with that return.
But, I’m long and strong. I’m not a trader. I don’t intend to sell any of my shares any time soon (if ever — they may pass to my children in my estate).
Now let’s imagine (with what I believe to be some high probability) that in 2020, when Anavex drugs gain sales in ever-expanding markets for an increasing number of human diseases, the share price hits $100. With that, in four years, I’ll have a 2,064% gain.
If that’s dead money, I’ll take it (and live well).
(But given the size of the global Alzheimer’s, Parkinson’s, and the other disease markets that Anavex drugs will successfully treat, I see a matured AVXL share price actually in the high hundreds or low thousands in 5 to 10 years.)
Now of course, I may be all wrong. The big Phase 3 double-blind study might turn out to be a bust. The Rett trial might do nothing for the little girls afflicted with that genetic disease. Anavex may go bust.
The chances of such are, based on my knowledge of Anavex science and all of the existing trials data extremely remote. But, I’m no investment fool. I’ve used only a few thousand discretionary dollars to make my AVXL purchases. My life will be little changed if Anavex goes bust (along with the millions who will continue to suffer and die from Alzheimer’s and other central nervous system diseases that presently are slated to fall to Anavex Life Science Corp.).
There Are Anavex Progress Reports
For those wondering about the status of Anavex progress, here is excerpted text from the “Catalysts 2017" page at this website: http://www.anavex.com/my_uploads/Anavex-June-2017-Presentation.pdf
Things that have occurred in 2017:
• Granted Orphan Drug Designations for the following indications: Rett Syndrome, Infantile spasms and Frontotemporal dementia
• Phase 2a - Report 57 week data at CTAD scientific meeting
Things yet to occur:
• Phase 2a - Updates on 104 week extension Alzheimer's study
• Phase 2a - Report PK/PD data
• Initiate Phase 2 clinical trial in Rett Syndrome (12 week, randomized, double-blind, placebo controlled)
• Initiate Phase 2 clinical trial in Parkinson's (12 week, randomized, double-blind, placebo controlled)
• Initiate Phase 2/3 clinical trial in Alzheimer's (6/12 month, randomized, double-blind, placebo controlled)
• Potential for clinical read-out by end 2017 / early 2018
• Complement current pipeline through in-licensing – ongoing
* * * * * *
The presumption that company officials (what few there are) are sitting around with their feet propped up delighting in some expensive cigars behind closed doors, failing to attend to corporate progress, is not supported by the many initiatives accomplished and projected.
Biggest of these, of course, will be initiation and conduct of significant new clinical trials including the Rett Syndrome trial (lasting only 12 weeks), a Parkinson’s clinical trial (also taking only 12 weeks), and finally, and most important, the big, 6/12 month make-or-break randomized double-blind placebo controlled Phase 3 Alzheimer’s study. Results from that not likely until sometime in 2018.
For share prices, the big Alzheimer’s trial won’t have any price-affecting data until late this year (at 6 months?) or sometime in 2018.
Sooner will be Rett Syndrome results, perhaps late this year. Then (with no details posted) is likely to be a 3-month Parkinson’s trial.
There is a high chance the short Rett trial will happen soon, and positive results should elevate AVXL share prices; particularly because Anavex already has FDA orphan drug status for the disease.
How long, then, will it take for the FDA to announce approval of Anavex 2-73 (or other drug)? The Cures Act in general, and specifically President Trump’s thrust to get quickened and enhanced new drug approvals for serious diseases should hasten approvals.
Following an FDA approval, how long might it take for the drug to become available, and how long might it be for widespread prescription sales?
Each AVXL shareholder will have to come with his or her own projections on all of these share price-determining factors.
For me, it is clear that the greatest AVXL share prices won’t be seen until starting to top off in 2019 or later. Quibbling over 25-cent share price variations right now is, for me, petty. Given the massive global markets for effective, enduring, safe treatments of the central nervous system diseases Anavex will provide, the multi-year wait will be adequately (well, monstrously) rewarding.
Is the Company Lying?
A mathematical impossibility as well as a factual misinterpretation that I blame on incomplete/misleading data presentation.
Combined Chances Prove Enduring Efficacy
Does Anavex 2-73 provide enduring, undiminished symptomatic stabilization or improvement for the entire period it’s administered (my claim); or, might the new drug lose potency for either a few or all who take it chronically? Will it stay strong throughout treatment, or lose effectiveness, as in the manner of Aricept? Why is my claim valid?
Thirty-two mid to moderate level Alzheimer’s patients participated in the Australian Phase1/Phase2 clinical trial. There were no reports of loss of efficacy over this 57-week period. All either remained at the initial symptomatic baseline, or cognition actually improved (no other cases of this of this magnitude and duration in any previous study).
Simply, there is not a shred of evidence that Anavex 2-73 loses potency. On the contrary, the evidence strongly supports the enduring efficacy thesis, that the drug works (or even improves symptoms) throughout chronic administration.
The claim that a much larger trial, testing much larger numbers of patients, is required to ascertain chronic efficacy is not supported by the Australian study. If this were a problem, even for only a portion of those on the drug, the plot of cerebral function would not have appeared in a rather straight, horizontal line, plotted against the 57-weeks of time. If the drug lost potency for some, the plot would have either declined (sloped downward toward the end), or the error bars would have widened at the end. Neither was the case.
The only chance that Anavex 2-73 might prove in a big Phase 3 trial to actually lose efficacy over a year would be that in larger populations, for some, this does occur, and that the Australian trial, merely by impossible chance, enrolled only people in which the drug did not lose efficacy. The chances of this are statistically miniscule. All in the Australian study retained efficacy, as will those in any larger study. The chances that only chronic efficacy responders were selected, and, by chance, any lose-efficacy non-responders were left out is tiny.
It’s not much of a factor, anyway. FDA does not require 100% patient efficacy for the approval of new drugs — just something better and safer than the current Standard of Care. Anavex 2-73 has those going away — as the big Phase 3 study will further affirm.
Not a Viable Competitor
Interesting report. Yes, a new Alzheimer's treatment drug combo being worked on. Nice effort, with a moderate chance, I think, of some efficacy.
But not a likely Anavex competitor for these reasons.
The new drug is RVT-101, or intepirdine, a molecule that prompts the production of acetylcholine, a critical molecule in the synapse between connected neurons. Alzheimer's reduces acetylcholine concentrations, thereby reducing nerve signal transmissions, resulting in cognitive decline and other symptoms.
Aricept (with which the new drug will be combined) is a Standard of Care drug for Alzheimer's. It's an acetylcholinesterase inhibitor. It breaks down the enzyme acetylcholinesterase, thereby helping to maintain adequately sufficient levels of the acetylcholine neurotransmitter.
Will this work? Will it control or suppress Alzheimer's symptoms? I'm rather certain it will. But it won't be an Anavex 2-73 competitor for the same reason Aricept will not be. Aricept really does work, it stops or slows the progressing severity of Alzheimer's symptoms. Wonderful, yes.
But only for a short period of time, only a few weeks or months. Accumulations of beta-amyloids and tau tangles continue unabated, and they overwhelm Aricept. It invariably fails to work after a moderately short period of time.
With this new combination, it's likely that symptomatic control or suppression of Alzheimer's symptoms will persist for a longer period of time than Aricept alone.
But here's why this combo will not prove to be an Anavex competitor. Anavex 2-73 continues to provide either symptomatic stabilization or reduction for the entire time it's been prescribed --- many months, with not a single indication in either humans or test animals of loss of efficacy with prolonged administration.
So, perhaps this new drug will get FDA approval. It may prove to be much better than Aricept, a current Standard of Care for Alzheimer's. But both physicians and patients will prefer Anavex 2-73, because of its enduring efficacy.
Mitochondrial Disease Costs are Great
A new report tells of the profound problems and costs of mitochondrial diseases (such as Rett syndrome, for which Anavex will be testing its treatment in an upcoming clinical trial).
https://www.eurekalert.org/pub_releases/2017-06/chop-mdh062817.php
When patients with these diseases are hospitalized, they incur high medical costs, and suffer higher-than-typical rates of comorbid diseases and in-hospital mortality. Researchers who analyzed those costs using national databases say their findings underscore the importance of developing preventive strategies and therapies for these illnesses.
Time Required for Genomic Analysis
One whole-genome analysis firm (Veritas) states, “The current turnaround time is 12-16 weeks upon receipt of a saliva sample.”
So, three to four months for total genome analysis. Requires only a saliva sample to begin.
Data Mining Doesn't Take Months
It has been proposed that the delay in Anavex data release has been caused by lengthy, detailed analyses. Don't think so.
There haven't been a bunch of guys sitting at dim lab tables with slide rules, pencils, and paper charts "analyzing" trials data in new, detailed ways.
21st-century data analysis uses complex, detailed, precise computer algorithms. Simply plug in the raw data numbers, let the computer "think" for a fraction of a second, and out comes chart plots and spreadsheets showing everything possible from the original raw data sets.
Now, of course, those algorithms are proprietary, unique and owned by whatever firm was hired to do the analysis. But it's ludicrous to think it takes month after month to extract useful data.
The reasons Anavex is holding the new derived trials data close to their chest is for other reasons, almost surely for competitive and negotiations advantages.
Well and good. My share price will, in time, elevate when Missling and company see fit to play their strong hands.
Why is Now the Time for Info Release?
I bought my first (very small) position in AVXL in December 2015. I've been waiting for good news and substantial price rises as long as most. Frustrating? Of course.
But it would be a bit much, I think, to claim that any of the Anavex principals, especially Dr. Missling, are negligent, remiss, or otherwise deficient in getting out public data on Anavex 2-73.
Like everyone else here, I have no inside information that can explain the company's lengthy "quiet period." Yes, we all look forward to the derived and analyzed pharmacokinetic/pharmacodynamics data that, most likely, will validate and strengthen the existing Phase1/Phase2 data from the Australian trial. With those yet-to-be-announced data, the validity of the Anavex story will be even substantially stronger.
But there is no plausible reason Missling et al. are withholding public release of new data simply to confound or slow up the Anavex 2-73 process. Utterly unreasonable, for a number of reasons; not the least of which is Missling's gigantic share holdings. Negligence or malfeasance on his part hurts him more than any shareholder posting here. Missling is not reveling his strong hand. The game's not there yet.
The Anavex team knows exactly what they are doing. Yes, as with all new drug approvals and marketing, it takes longer than anyone, company officials, shareholders, or patients, would wish. But when the final chapters of Anavex 2-73 FDA approval story are written (next year or after), the wait will have been financially rewarding.
Rome wasn't built in a day....
Missling is our Caesar in charge. Quite a financial and medical edifice Anavex will be. Given the global markets for the Anavex drugs and multiplicity of diseases they will both prevent and treat, Anavex Life Sciences Corp will be among the biggest Big Pharmas ever. I foresee AVXL share prices somewhere in three digits.
Intelligent Query, Plant-based 2-73 Source
Your question about eventually sourcing Anavex 2-73 was very appropriate. As you discovered, other drugs and molecules are being nudged from genetically-manipulated plants. It's a new chemical synthesis process.
I should have made myself more clear. Botanical synthesis of Anavex 2-73 is not altogether impossible or improbable; only that it will take a major plant breeding and genetic manipulation effort. That will be costly (but perhaps worthwhile) and lengthy (nothing near term).
The real question (very important) is the costs and volumes of Anavex 2-73 production, by any means. From my rudimentary knowledge of organic chemistry, it appears the molecule can be conventionally produced in commercial amounts. Some entity, probably a contract chemical synthesis company will have to undertake this. There are firms in, among other places, the US, Germany, and Japan, skilled in organic molecule production.
It's just one other thing the in-house team of Anavex experts will have to arrange, once FDA approval for any disease occurs.
I don't see this as an inhibiting factor.
Anavex 2-73 Very Complex, Botanical Source Unlikely
Is it possible for A2-73 to be produced and manufactured via Plants??
No Real Anavex Competition
Yes, as noted in the referenced URL, a number of Big Pharmaceuticals are moving more Alzheimer's drug candidates into trials and hoped-for FDA approvals. Are any of these companies or potential drugs that can compete with Anavex and Anavex 2-73? Could any of those other companies eclipse Anavex for Alzheimer's, making an equity position in Anavex unfavorable?
If Anavex were attacking Alzheimer's like all the other companies, targeting protein wastes (beta-amyloid, tau tangles), the game would be an even match.
But the game is not even or fair. Anavex's drug targets the root-cause, early cellular dysfunction, not the end-result disease problem of the toxic accumulation of waste proteins. Two entirely different approaches.
As known by anyone having done the slightest due diligence on proposed or clinically-tested Alzheimer's treatment drugs, of the many clinical trials done (at great expense, each) with waste-clearing drugs, not a one has ever succeeded; failures because of simple inability to cause protein waste clearing, or severe, debilitating averse events (side effects).
Early clinical results of Biogen's aducanumab, another waste-clearing drug, seem to show useful waste-clearing outcomes, better than any previous. But a side effect, at least in some, was brain swelling. In larger Phase 3 trials, brain swelling will be a critical factor; one not very promising.
Anavex 2-73 in Phase1/Phase2 trials for safety and dosing levels (the Australian trial), showed unmatched stabilization or improvement of cognition in Alzheimer's patients. Moreover, adverse events were very mild and reasonably infrequent; not an approval-confounding or good-use factor at all.
So, no, Anavex has no competition in any picture of known potential new Alzheimer's drugs. Anavex 2-73 fixes Alzheimer's problems early in the disease process, before they advance to debilitating levels (prophylaxis), and for those with mild to moderate Alzheimer's, the drug stabilizes or improves disease symptoms. No other drug, in trials or approved, has been able to do that.
Alzheimer's a World-wide Problem (and Market)
Good point. We are too narrowly focused on just the US and the FDA as the sole loci for Anavex success.
It is (or will soon be discovered) to be in the interest of virtually every country in the world to have a solution to the ever-expanding Alzheimer's problem. The disease is not confined to just the US, or even the developed world. Everyone in every culture ages, and all are vulnerable.
The only viable solution is prophylactic (preventative) and early-stage treatment with Anavex 2-73 (and perhaps later with Anavex 3-71).
The Anavex market is global.
What's an MTA? I don't know.
Requested Dosing Extension
Here's another extremely revealing statement from the article:
The extension phase was originally planned to last 6 months, but patients and caregivers wanted to continue on the medication, so the company extended it to 12 months. It is ongoing.
Patent application excerpts:
The pharmaceutical products being with anti-cancer, anti-metastatic and anti(chronic)inflammatory action.
The invention may also include the preparation of pharmaceutical products with neuroprotective, anti-amnesic anticonvulsive, antidepressive and nooanaleptic-elevating vigilance and anti-fatigue actions for the first two entities and sedative-anxiolytic action for the last entities.
...with anti-cancer, anti-metastatic, anti-(chronic) inflammatory, neuroprotective, anticonvulsant, antidepressive, nooanaleptic and anxiolytic action....
The molecules mentioned above can be used as anti-cancer drugs, either alone or in combination with conventional anti-cancer drugs. They can also be used as diagnostics (sigma receptors are increasing in most of the different types of cancer cells) and as anti-metastatic drugs, since they inhibit the binding and migration of cancer cells via tumor cell membrane reorganization and inhibition....