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Cellular Homeostasis, Or Other Mechanisms, Too?
Are the other products in the Anavex pipeline focused on cellular homeostasis or is it a different molecular reaction that occurs with these drugs,....
But those of us with considered AVXL positions retain a persisting grin...
...one we'll display on the way to the you know where in a few years.
Not Similar In Any Way
Bryostatin-1 (Neurotrope) is in no way similar or comparable to Anavex 2-73. Bryostatin (if it proved safe enough to use---it didn't) works at a downstream edge of the Alzheimer's disease process, working to stop or remove waste protein accumulations.
Uniquely, by entirely different mechanisms of action, Anavex 2-73 re-connects and restores normal mitochondrial/endoplasmic structure and function, thereby restoring normal neuron function. It works at the upstream edge of Alzheimer's, where the disease process begins.
Bryostatin exhibited disqualifying adverse events (side effects). Anavex 2-73 has never shown any of those, either in lab animals or humans.
A blemished apple/sweet orange comparison.
Be Careful With “Homeostasis.”
Understandably, the term “homeostasis” is appearing frequently in postings here.
Yes, Anavex 2-73 does restore a specific form of homeostasis inside aberrant, poorly functioning neurons.
But specifically, homeostasis is understood by practicing biologists to be, “...the property of a system within an orangism in which a variable, such as the concentration of a substance in solution, is actively regulated to remain very nearly constant.”
Homeostasis requires two things, presence of a variable, something that can change, and a mechanism that regulates, controls, or suppresses such changes.
Classic textbook case is thermal homeostasis, where the body attempts to maintain a core temperature around 37 degrees Celsius (98.6 degrees Fahrenheit). If temperature drops, one is chilled and prompted to put on some more clothes. Shivering heats muscles and tissues. If heated, some clothes come off, and the body sweats, promoting evaporative cooling on the skin. In an infection, the body hikes the homeostatic temperature, bringing on a fever, to reduce optimal microbial growth temperature. Most bacteria and viruses function best at 37 degrees C, are less functional at temps above that. Except when excessive, fevers are normal, healthful body mechanisms working against infectious agents. Thermal homeostasis is varied by the body.
It is not accurate to claim or imply that Anavex 2-73 restores any and all cellular homeostatic processes. There are so many, mostly unaffected by any sigma-1 receptor agonist, natural or synthetic.
There are a multitude of intracellular variables that must be keep relatively constant. Concentrations of ions, sugars, electrolytes, proteins, etc. are maintained. Of course, disease malfunctions occur when concentrations change beyond normality, when molecular or ionic homeostasis is not maintained.
So, how, then can we concisely and more accurately refer to the unique, therapeutic properties of Anavex 2-73, other than a generalized “homeostasis?”
The simplest, most accurate phrase might be, simply, it “restores neuron function.”
Few people have ever heard of, or use the term "homeostasis." "Normal function" is instantly understood by everyone.
Anavex 2-73, a profound new drug that restores neuron function. That covers it rather completely (at least until restoration or fixing of other disease modalities is demonstrated).
All of the Anavex target diseases involve, are caused by, neuron dysfunction. Our drug restores neuron function, simply. Nothing better could happen with these diseases.
I Retract Rett Trial Concerns. Murine Data Positive!
http://www.anavex.com/my_uploads/ANAVEX-2-73-as-a-Potential-Treatment-for-Rett-Syndrome.pdf
Fireman, thank you for bringing this Anavex presentation to my attention. I was negligent in not finding and studying it.
In short, it thoroughly affirms my earlier contention that the Anavex people must have had very positive treatment results with lab rodents for the treatment of Rett-like genetics and symptoms with Anavex 2-73.
In the Rett-like mice, as expected, the drug failed to provide complete relief from the many symptoms of the rodent Rett-like genetics. But relief was sufficient—if it occurs to the same degree in humans in the upcoming trial—that FDA approval appears absolutely certain.
The presentation, as it should, first noted the profound safety, lack of high-level adverse events, in the Australian human trial with Anavex 2-73. And no adverse events in the mice were noted or presented.
The positive outcomes are summarized on slide 30:
Administration of ANAVEX 2-73 results in both significant and dose related improvements in an array of behavioral paradigms in the MECP2 HET Rett syndrome disease model.
These behavioral paradigms measure different aspects of muscular coordination, balance, motor learning and muscular strengths, some of the core deficits observed in Rett syndrome.
The efficacy of ANAVEX 2-73 in additional different disease-relevant models — Infantile Spasms and Fragile X, Autism-related Disorders — in combination with existing clinical safety data supports exploration of ANAVEX 2-73 as a potential therapeutic in these disorders.
Clinical efficacy may also be evident in patients with CDKL5 mutations given that this gene has been implicated in both Rett Syndrome and X-linked Infantile Spasm Syndrome.
Yes, Seizure Control Alone Will Prompt FDA Approval
I'm no expert, by any means, on Rett syndrome. I've pondered the outcomes of a failure of the Rett syndrome trial (presuming, however, that the company knows from the start, from animal data, that it will be a big success).
I questioned the possibility that Anavex 2-73 might be able to fully restore or create normal nerve and body functions, as many of these not functioning in Rett syndrome don't appear to be open to sigma-1 receptor agonist treatment.
We all hope that's not so, that Anavex 2-73, by whatever means, might bring full health to the children with the disease.
But, I, too, think that if suppression or termination of epilepsy in Rett patients were all that the up-coming trial might demonstrate, FDA approval would be forthcoming. Safe suppression of this set of symptoms would be a marked quality of life improvement, worthy of Anavex 2-73 usage.
Have Not Delved into Rett
...it would seem that normal development has been disrupted by some aggressive form of neurodegeneration.
Ok, A Potential Big Negative (Or Not)
I’ve pondered this, that the base cause of Rett syndrome is genetic, an aberration in the genome the little girls inherit from their parents’ gametes.
Therefore, there can be no normal homeostasis to “restore.” None there to begin with.
In most Alzheimer’s cases the person was in general neurological health in earlier years, when organelles in the neurons functioned normally. Waste-clearing enzymes were synthesized and they did their job. But, with age, endoplasmic reticula began to break away from mitochondria, and Alzheimer’s symptoms set in.
Unfortunately, in Rett, there is no turning back to a better time, when things were working normally. Rett is a de novo (first time, no ancestral occurrence) mutation. In Rett, the production of a specific protein (MECP2) is genetically disrupted, complicating normal brain development.
How, then, might the known Anavex 2-73 sigma-1 receptor agonist work to fix this broken-from-the-start arrangement? I don’t see how this genetic problem can be fixed by restoring the mitochondrial/endoplasmic reticular connection. That works wonderfully in Alzheimer’s disease. But for Rett, there must be some other, yet undisclosed mechanism of action. I have no idea what that might be.
Not that my ignorance of the matter has any application, but it might be that Anavex 2-73 has a reduced chance of effectively treating girls with Rett syndrome; that, perhaps, it will provide only small or minimal benefits. Could up-coming Rett trial results turn out negative or meager? If so, what would be the impact on the future of Anavex Life Sciences Corp?
It could be imagined that a Rett trial failure would portend consequent Parkinson’s and Alzheimer’s failures. End of company. Has Missling bet the company’s future on a tiny population of diseased girls, for which the drugs might not work? How so?
One of two possibilities. The quick Rett trial (just 12 weeks) is a bet that results will be good, pushing things along for the other two, much more significant trials. A corporate gamble, perhaps, for a quick return?
Or, do the experts in the Anavex labs have information of yet-undisclosed new Anavex mechanisms of action that actually fix certain genetic errors? Ponder the implications of that.
Have Anavex scientists dosed some genetically deformed or deficient lab rats with Anavex 2-73 and found they then took up normal health or physiological function, by some new mechanism of action?
Frankly, I can’t see Missling and Company heading into an early, company-affirming clinical trial for which they haven’t solid understandings of just how it will turn out.
The science behind Anavex’s Rett therapy might be really big and new; portending a whole body of new applications for all sorts of genetic diseases. The Anavex story may turn out bigger than we presently imagine.
The Rett trial; bust or boom. I think, the latter.
No, Anavex Not A Vaccine; A Preventative
Didn't make myself clear. Of course, Anavex 2-73 is not and will not be any sort of a vaccine, prompting the body to create microbe-killing antibodies.
The point (not well made) was that governmental regulations exist which impose certain medical procedures on portions of the population. It is not unreasonable that, for other reasons (savings of Medicare, health insurance costs, etc.) the taking of Anavex drugs might become mandatory, either by regulation (less likely), or by insurance company contrivance (very likely).
Work for us, at this company. We provide health care insurance, a nice, cost-saving fringe benefit. But our health insurance company won't cover anyone who doesn't pop a prescribed Anavex 2-73 every morning at breakfast. Our health insurance company will provide the prescribing doctor, the physical exam, and the on-going supply of the Anavex drugs. You just gotta pop 'em once a day as long as you work here.
We, the company, will have markedly reduced health insurance cost benefits for our employees, and moreover, we find that employees taking 20 mg of Anavex 2-73 sleep well, so they work well during the day. No drowsiness at our company, thank you Anavex. And our 3rd-shift people sleep well during the day, and come to work at 11pm, giving a full night's effort. We all win, do we not? Sign right there, on that dotted line. Welcome to employment at Bargledorfer Inc.
A Vaccine Equivalent?
The question of who and how many might eventually take Anavex drugs, prophylactically, to prevent the onset of Alzheimer's and the other degenerative diseases Anavex drugs will be preventing or treating is a good one.
Consider the social and governmental costs of expanding numbers of Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (Lou Gehrig's disease) and the others Anavex drugs might prevent or treat at an early stage.
Presently, little kids are required to be vaccinated, with any number of disease-preventing vaccinations, so as to keep them healthy and minimize health care costs.
Why, then, wouldn't "vaccinations" of Anavex drugs be required for those entering middle age, so as to forestall all of the costs of the diseases being prevented?
Seems logical and appropriate. Mandate good health in advancing years. Period.
Hope Anavex Drugs Are Low Cost, for Patients.
I concur. Regardless of whatever financial rewards any of us might gain from full FDA approval and widespread use of Anavex drugs, for me, the primary concern is the widest and best use of Anavex drugs.
In my for-fun conjectures of future Anavex revenues, share prices, and dividends, I've generally focused on a presumed, low-end $5 a day income per Anavex patient. This is way less than all those fancy, read the warnings drugs advertised on the evening newscasts.
It would be far better, however, if people could take Anavex drugs for, say a buck a day, in the manner of an over the counter analgesic, to get the best social and societal return.
Even at the very lowest potential Anavex drug prices, I'll still reap rewarding investment returns with my small AVXL position.
Ethically, we all have to personally rank our desires and perspectives. Each will have to, very privately, determine his or her viewpoint on the matter. We are dealing with life and death ethical matters here.
One Grand for an AVXL Share? Come On.
Ok, for fun (Did you read that? For FUN.), let me lay out some numbers. Readers, on their own, with their own individual numbers and perspectives can tweak and amend these as they see fit.
First, let’s call the game and toss in the towel. What happens to the share price of AVXL if the three upcoming clinical trials fail? Simple. On your spreadsheet or calculator, enter the number of dollars you’ve used to buy your AVXL position, the multiply that times 0. End of game. It was nice, while it lasted.
Or, presume that all three trials turn out well, with favorable efficacy and adverse events data. That would mean Anavex 2-73 gets approved by the FDA and will be used to prevent or treat Alzheimer’s, Parkinson’s, and Rett syndrome. What might be the pecuniary implications for AVXL shareholders, present or future?
In valuation calculations, a base number must first be decided, the eventual number of outstanding AVXL shares that can be traded, the number of shares to which dividends will be divided and earned.
Presently, according to the Ihub Anavex data box, there are presently 42,100,000 shares being traded. For our calculations, we could use that hard number. But to be conservative, to account for future share number dilutions (should there be any), I’m going to presume an eventual outstanding share quantity of 100,000,000. If the share count stays at 42.1 million, just multiply projected share prices and dividends by about 2.3.
Ok, 100 million shares will be in play. Next, let’s try to figure out annual corporate revenues. To do that, we will first need to know the sizes of potential patient pools. How many have the diseases Anavex will treat?
Let’s start with the biggest affliction in the Anavex spotlight, Alzheimer’s disease.
First, what are current total Alzheimer’s care costs? One online source says, “The cost of caring for Alzheimer’s patients in the U.S. is estimated to be $236 billion in 2016. (Alzheimer’s Association) The global cost of Alzheimer’s and dementia is estimated to be $605 billion, which is equivalent to 1% of the entire world’s gross domestic product.”
The costs for this one disease are monstrous, and will only continue to grow as populations continue to age. Keep these numbers in the conceptual frame.
An online source claims that about 44 million have Alzheimer’s today, across the world. Not all of these will be taking Anavex 2-73. Let’s presume only half, rounded to a nice 20 million.
Next—and this is where things get really iffy—we need to estimate how many dollars Anavex Life Sciences will gain each year from each Alzheimer’s patient.
On the high end, it would not seem unreasonable they could charge just half of annual treatment costs. One source claims $60,000 is a typical annual care cost. So, at a high end, charging but half of conventional care and treatment costs (presuming Anavex treatment allows a normal, unassisted living style), Anavex would reap $30,000 times the number being treated. Instead of 20 million, let’s presume only 10 million, worldwide, take and pay for Anavex 2-73. 10,000,000 x 30,000 = 300,000,000,000: Three hundred billion dollars of annual corporate income.
But that seems high. The cited estimate of total Alzheimer’s costs in the US each year is $236 billion. But there are equal or exceeding numbers of Alzheimer’s patients in Europe and the rest of the developed Western world. So, this number may be reasonable.
Still, seems way too high. I like to undershoot the numbers, so resulting errors emerge at higher levels. Let’s say Anavex Life Sciences gains but 10% of those income revenues, a mere $30,000,000,000, thirty billion dollars a year.
Or, punch it out this way. Presume that Anavex reaps just $5 dollars of income per day per American Alzheimer’s patient. A source says 5.5 million Americans have the disease. It is reasonable and conservative to presume an equal number of people in other Western countries have the disease. So, let’s work with 11 million patients, paying $5 a day for their drug from Anavex each year, worldwide.
In a year, Anavex takes in 365 x $5, $1825 per patient. Let’s presume $825 are manufacturing, advertising, taxes, and distribution costs, with a straight $1000 margin. In a year, that’s a corporate profit of 11million x $1000; a nice $11 billion.
Again, these latter numbers should be at the low end. Higher drug pricing would bring in proportionately more dollars. Readers can punch those on their own. Here, I’ll stick with these low-end numbers.
So, just from Alzheimer’s treatments alone, Anavex would take in $11 billion. How much of that might flow down in dividends to AVXL shareholders? Again, I prefer to be very conservative; I’ll presume just a 20% flow down, 2.2 billion dollars.
How much is that per share? 2,200,000,000 / 100,000,000 = $22
That’s for Alzheimer’s. What about the next biggie, Parkinson’s?
About 60,000 Americans have the disease. For our conservative projections, let’s presume Anavex will be treating just 120,000 people in all the world with this disease. Let’s presume again the cheap $5 a day patient drug cost (going straight to Anavex coffers). It’s the product of 5 x 365 x 120,000, a total of $219 million. Let’s presume, as above, that about 45% of that are pre-dividend costs, yielding a margin, profit, income of $219 million x 45% = $98.5 million. We can round that to a corporate annual margin from Parkinson’s at $100,000,000.
With that, Anavex is now clearing $11.1 billion a year in profits from both Alzheimer’s and Parkinson’s.
For Rett syndrome, let’s not go there. So few have the disease (thankfully), it could only be a minor fraction of any Anavex profits. We’ll presume none, here.
I said, I like to keep things very conservative, allowing actual events to play out at higher probable levels. With that, I’ll terminate this discussion with just two projections: AVXL share price, and annual per share dividends.
First, the dividends. With these calculations, Anavex Life Sciences Corp, each year, has big revenues of $11,100,000,000. I’ll conservatively presume that only 20% is distributed in dividends to shareholders. That’s $2,220,000,000. With 100,000,000 outstanding shares, that would yield $22.20 per share.
Resulting share price? At a 10:1 PE ratio, an AVXL share would trade in the $222 range.
That, to me, is the absolute lowest eventual AVXL price. It does not include any of the other diseases Anavex may treat. Two or three times as many dollars may flow down to shareholders, with doubling or tripling of these dividends and share prices. The 10 to 1 price to earnings ratio may be way too low for the present market. Many equities are presently at 20 to 1, so future AVXL share prices would be doubled, in the $400 range.
But, instead of just 20% of corporate revenues flowing to the bottom line, what if 60% did? That would, at the lowest income numbers here, yield an annual dividend of about $60 per share. At a 10:1 PE ratio, that’s a $600 share price. At a more current 20:1 PE, that’s a share price of $1200.
All of this is for only Alzhheimer’s and Parkinson’s, with minimal numbers. What if Anavex drugs potentiate and safely enhance dozens of other drugs, for cancers, cardiovascular diseases, psychiatric conditions, etc.? Might the number then be multiplied by an order of magnitude, x10?
And maybe eventual outstanding shares rise only to 50 million, not the 100 million used in the calculations above? Double, then, all the final price numbers.
And, finally, what if Anavex 2-73 or an analogue simply and safely solves the insomnia problem? One can, at this point, only guess (not estimate) the results of that for the company and Anavex shareholders.
An eventual $1000 share price is not unreasonable, by any means. It could be much more, all depending....
21st-Century Rules
These are, by no means, the only definitive reasons the up-coming Phase 3 clinical trial of Anavex 2-73 against Alzheimer’s can validly involve many fewer patients than the just completed Biogen aducanumab study. The crucial, but not sole, issue is that that study was arranged and conducted under old FDA drug approval regulations, which required much more lengthy and larger trial cohort populations.
New FDA rules will allow and encourage more sophisticated symptom and physiology analysis. Twenty-first century trials protocols, as it were.
Secondly, aducanumab is a monoclonal antibody, that directs immune system processes to bind to and remove the waste proteins of Alzheimer’s. Any number of monoclonal antibody and immunological drugs targeting Alzheimer’s symptoms have failed, often with severe adverse events. Hence, the advisability (requirement) of a large clinical test population, all under the old rules.
I would add, should Biogen’s new drug, aducanumab, have clinical efficacy, get approved, and come to market, it is still a monoclonal antibody. It will certainly have side effects at certain doses, is unlikely to work in all patients, and lastly, it targets the down-stream, end-of-disease stage of Alzheimer’s, after the waste proteins have both formed and have been accumulated.
Our drug is substantially different, in these essential ways. First, few or no adverse events (side effects) at any level to preclude or terminate Anavex 2-73 dosing. No comparison to drugs that attempt to manipulate the immune system.
Anavex 2-73 attacks the Alzheimer’s disease process at its very start; or, when used as a prophylactic (preventative) even before the disease sets in symptomatically. It fixes disconnected neuron organelles, allowing them to resume normal, healthful function; before the disease consequently becomes debilitating or lethal.
Monoclonal antibodies have to be injected, so as not to be pre-digested before absorption. Anavex 2-73 is taken with ease, orally.
Two very different drugs. My bet (figurative, of course) is for the approval, medical acceptance, and widespread usage of Anavex 2-73. Apples (with some blemishes) and oranges.
Buyers Can Wait. I Just Bought Mine.
I just took my last AVXL position. Outa funds now.
Got my shares after the price ascended 2.7%. If I had gotten at the very opening, woulda had a few more shares (which I think will be in triple digits in time).
But, I've discovered in my previous buys, last year, my purchases can turn the AVXL market right around. I seem to mark, even control, the high of the day.
Prices, now, or soon, should decline.
Glad to be of service to those buying any AVXLs for the rest of the day.
Shall It Happen? If Not, So Be It.
Yes, my posted visions for Anavex Life Sciences Corp and 21st-century medicine are glowing, to say the least. Most rational readers would dismiss my prognostications as mythical imaginations, little supported by what they can see just yet.
That’s fine. I’ve taken a small AVXL position and intend to hold it for the rest of my days. Should the Anavex story develop and mature as described, I could be looked at as something of a visionary.
If things turn around, if trials results are meager and FDA approval of Anavex 2-73 fails, I’ll be regarded as but another online crazy, entertaining and promoting extraordinary outcomes for a held equity position. There are guys like me on most Ihub boards, I would imagine.
Nonetheless, I don’t post my Anavex thoughts in any way to pump AVXL share prices. In fact, as mentioned, I intend to complete my AVXL purchases today or tomorrow, with a few more dozen in my portfolio. I’m hoping the share price drops today, so I can buy a few more with my meager funds.
Readers, individually will have to decide for themselves if my postings are mere entertainment, or, plausible and evidence-supported visions.
Never, ever, invest in any no-revenues start-up with funds you can’t afford to lose. Like all start-ups, Anavex is a speculation. But for many of us here, a well-informed one, with the greatest prospects. The science is solid, unique, and transformative. The management is top-line. No debt, ample operating funds. Significant collaborations, known and to-be-announced. And the markets are gigantic and global.
Let’s watch what happens. I’m buckled in, ready to pull the parachute if needed. Don’t see that in any way, just yet.
Think of Health Insurance Companies and Anavex
McMagyar, I’ve punched very similar numbers myself, using very simple entry data.
Those data are not unrealistic, should Anavex 2-73 prove to be both the prophylaxis (preventative) and treatment of central nervous system and other diseases that appear so probable, based upon both murine (rodent) and human data and experiences.
Consider, then, the involvement of health insurance companies should Anavex 2-73 prove to be so helpful in preventing and treating just the diseases Alzheimer’s and Parkinson’s, along with some others to be discovered (cardiovascular diseases and cancers, particularly, have in-the-pipeline or in-the-lab indications).
With care costs for Alzheimer’s, Parkinson’s, and the many other geriatric diseases dramatically reduced, just what would health insurance companies pay for their insured clients to take Anavex 2-73?
Would this scenario be plausible? Health insurance company X announces that its annual premiums will be reduced by 50%. But only if clients dutifully take a dose of Anavex 2-73 once a day. The drug will be provided by the health insurance company, which has cut a deal with Anavex Life Sciences Corp for x-million doses in the coming year.
With that, insurance company pay-outs to physicians and doctors plummet. The health of geriatric (even middle-aged) clients massively improve, as CNS, cardiac, and cancer diseases become rather infrequent.
This rescues Medicare and Medicaid.
Anavex Life Science Corp revenues ascend into the many billions, with dividend flow-down revenues to AVXL shareholders.
Everyone but physicians, other pharmaceuticals, hospitals, and extended-care and nursing homes benefit.
A transforming revolution in so many ways. Let’s watch it happen. We can tell our grand children (in our then healthful old age) that we were there at the beginning, that their college costs will be paid for by we grandparents from our AVXL proceeds and earnings.
Just Great
Talon, thanks for the explanation of the name. I'm not particularly familiar with that aircraft, but the name sounds perfect for it.
As it happens, in my field biology studies (unrelated to my biology teaching career) I've trapped and banded many dozens of wild Red-tailed Hawks. I've studied them from Alaska to Maine, and particularly in my Midwest home state.
I also trained and hunted rabbits with Red-tails for about 40 years. Just a great, regal species of raptor, as you've observed with your wild hawks. Their ability to maneuver in the air in the pursuit of prey is always stunning. It has been an honor to be able to work with this species in so many ways.
A neurological spasticity that set in during my latter years has caused leg stiffness that no longer allows me to train or hunt with hawks. My falconry days are over. But they were great and fulfilling. I've been rewarded with their memory.
Related to Anavex, a French scientist treated transgenic rats wherein he had inserted a set of genes that cause my condition, hereditary spastic paraplegia, and they, like myself, then walked slowly, with very stiff back legs. When fed or injected with an Anavex sigma-1 receptor agonist, the rats soon resumed normal mobility, no longer hindered by the genetic spasticity. The disease is neurological, where the long motor neurons of the spinal chord no longer function properly (mitochondrial dysfunction) and become hyperactive, continually sending tighten-up messages to the adductor muscles on the inside of the calf (among some other, lesser bad signals).
You can see, then, why I have a particular interest in the coming to market of Anavex 2-73. Should that happen (I see no reason it won't), very likely I'll be able to resume normal walking and will put away my wheeled walker. I'm too old to take up falconry again, even if I could do the necessary walking. Either way, with or without the Anavex drug, I will be able to continue my other field biology projects for a NASA contractor. Would just be nice to be able to do that without the walker.
Monday Will Be the Day.
Talon (by the way, as a falconer, love your name), I’ve been pondering my elevating powers over the AVXL market. Many planning to take (or liquidate) AVXL positions follow my postings here very closely, I’m sure, allowing my deliberations to so strongly influence the direction of AVXL share prices.
Right now, the rumor is circulating that Falconer on the Ihub board is going to take a new AVXL position on Monday, with a new buy. That, should we think, will prompt so many others to get in before the resulting price ascent begins.
So, let’s watch it happen. Share prices should begin to elevate in mid-morning, with increasing ask volumes and prices. Trade volumes will increase throughout the day, with a close at the high of the day.
After the close, Anavex watchers will want to know what caused the Monday price gain, and the secret will be out. Falconer bought some. If he decided to do that, especially in the face of the persisting fudstration on the Ihub Anavex board, something big must be about to occur. That Falconer guy really seems to be on top of the Anavex story. He makes predictions and statements that are too good to be false.
[Ok. I’ll awaken from my nap. That drink my wife mixed for me really hit the spot.]
Exactly. Will Go Forward As Described
Plexrec, you've seen things just as I have. I'll make my small AVXL purchases next week, probably Monday morning, after watching the trend, if any, after the opening. If it heads up, I'll probably jump in and make my buys. (That will very much influence the market. Just after my buy, the price --- as so often before --- will turn around and drop below my buy price. I seem to have great market influence powers. I can buy a few dozen AVXLs and rather immediately halt any price climb.)
Therefore, my AVXL buys next week should stabilize or depress AVXL prices.
But, as we both know, those are mostly immaterial to our real goal: substantial share price gains, even big dividends, many years down the road.
Tom, No Disrespect Intended.
My thanks for your detailed discourse on the matter.
My next purchase (probably my last --- have a much larger, earlier core position, to be held for the longest period) is tiny, just for some fun.
Thanks for your postings. They provide a diversity of perspectives on this board.
Gonna Buy a Few More. When Should I?
Just got a few discretionary bucks to my brokerage. When do any of you technical analysts see I should make my purchase of a few dozen AVXLs? Right on Monday, or are my odds for a lower price later in the week? Later in the month? What are the odds? I understand, none of this is solid or assured; merely technical (chart) trends. Hazy stuff, at best; but sometimes with clear directions (but not to me).
I can't make heads or tails of those colored spaghetti charts. You TA types can interpret those plots. Any recommendations? I'm in no rush, will wait as long probability suggests. But don't want to miss a big run-up, either (not that I think any such thing is imminent).
Yes, There Is.
There is no need for rats.
Missling Knows --- More Than Any of Us
Can you or someone relay this to Dr Missling, in case he might not be aware of it?
Thanks, Posters, For The New Collaborations Perspective — BIG!!
Thanks to all of you who have posted thoughts on how Anavex molecules might be mixed with existing drugs and pharmaceuticals, for two good reasons: a) to strengthen and prolong Anavex patent rights on their proprietary drugs, and b) to enhance and facilitate improved existing-drug treatment outcomes.
I’ll not comment on the patent issue. I have no expertise on that.
But your postings have prompted some conceptualization thoughts. Synergistic collaboration of Anavex and any number of drug and pharmaceutical companies, where Anavex molecules are advantageously combined with existing drugs, may prove to yield the greatest financial returns for Anavex Life Sciences Corp and its share holders (most of us here). Roughly, here’s how I now see it, beyond the substantial outcomes of eventual FDA approvals for Alzhzeimer’s, Parkinson’s, Rett, and the several other central nervous system diseases with giant circles now on the Anavex dartboard.
Consider these facts.
1. Anavex 2-73 works in small concentrations, requiring small doses.
2. It readily crosses the blood/brain barrier.
3. It penetrates nerve and other cell types, and functions in the intracellular environment.
4. It chaperones, re-arranges various cellular chemical sequences and pathways.
5. It is orally administered, without digestion or loss.
6. It has no side effects of consideration.
7. Many drugs require large doses for efficacy, approaching or transcending a side effects threshold.
8. Most drugs or pharmaceuticals, likewise, strive to re-establish normalized cell or system chemistries.
With these considerations (there are others, certainly), the following can be intelligently envisioned.
Any number of currently approved drugs with dosage, side effects, and efficacy issues might well be markedly improved by the concomitant administration of any of the several Anavex pipeline molecules. It would be synergism, where two or more disjunct factors, together, cause outcomes greater than the elements by themselves.
Take some present that drug works. A cancer drug, for example. Its dosages have to be carefully titrated and monitored so as to both attain efficacy and avoid severe adverse events. To suppress the cancer, get the patient as sick as possible on the drug, to allow it to work effectively, at the highest tolerable dose.
But in this, case an Anavex sigma-1 receptor agonist is co-administered, and lo and behold, new drug traits emerge. The Anavex molecules have normalized cell chemistries (at least to a degree), which then facilitates the drug’s innate mechanisms of action. Lower doses are needed, thereby obviating or reducing the side effects. Better treatment outcomes, with fewer side effects, with smaller or less frequent dosings.
Might that not be a holy grail, as it were, for any Big Pharmaceutical? Anavex molecules fix and improve any number of existing drugs. Imagine the market if, say, only a few cancer chemotherapeutics were so enhanced by an Anavex molecule.
Let’s see about this. I’m contending (mark my words, note this post), that research will eventually appear with sound data showing that Anavex molecules dramatically change the pharmacodynamics and pharmacokinetics of many existing drugs, yielding substantial and enduring new treatment protocols and outcomes.
The Anavex revolution in 21st-century pharmacology will extend exponentially beyond just a few central nervous system diseases. The medicine and pharmacology of the remaining years in this century will cause the medicines and drugs of the last century (where we are just now) to look as coarse and primitive as did the medicine of the 19th century to those at the turn of the millennium.
Anavex, a millennial change in medicine. Let’s watch it happen.
All Those Mutual Funds Fooled, Too, Eh?
You contend that "this board" is unknowing of the actual, disqualifying truth of Anavex Life Sciences Corp.
Be that as it may. You failed to also include the several institutional owners of AVXL shares. Collectively, they and those of us here are a pretty ignorant bunch, are we not? Most of us here have placed at risk probably but a few thousand dollars with our AVXL positions, money we knew from the start might be at risk. This is a pharmaceutical start-up. We knew and know the risks.
But what about those mutual fund and other financial institution managers, who placed on the line millions of dollars of external investors' dollars? Tell us, please, how did they get as bamboozled by the Anavex story as so many of us here? Like yourself, aren't they smarter about these sorts of things? Anavex Life Sciences Corp certainly isn't the first or only pharmaceutical they've taken a position in.
You'ya gonna believe? The continuing question for all of us.
They "Know," But Don't Believe (Yet.)
Period.
It Already Has Two Names
Anavex 2-73 already has a name; well, two, in fact.
Here, it's known as Anavex 2-73. Quite fine. There will be no need to confuse matters by working up some new, alternative name. Anavex 2-73 will work and be remembered a whole lot better than some contrived new name --- such as primoneurocongellomab. You heard that here first (and never again, I hope).
Chemically, the molecule has the formal name of tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride.
Readers are free to use which ever they choose.
Autism and Vitamin D
This is off topic. Delete if appropriate.
I do not intend this to be any sort of expanding side issue. Delete it immediately should this thread wander off.
This is not a cure for autism. But it's worth considering as a moderate treatment. In the case of children in utero or newly-born, it is very promising and important.
There is a large negative correlation between autism and serum vitamin D levels. The majority of autistic children, at least in the first formative years, have low serum levels of vitamin D, less than 20 ng/ml. Many are far below that. Parents and physicians should test for serum vitamin D levels, and supplement with vitamin D-3 (not D-2, poorly absorbed, not as effective) to attain a minimum 30 ng/ml. For young children, this would be daily intakes in the range of 2000 IU per day. Older children would be taking 4000 to 5000 IU of D-3 per day.
I'll go no further. Those interested simply need to conduct a detailed online information search on autism and vitamin D. There will be many sites that claim there is no correlation, but they are unsupported by hard demographic data, merely textbook conjectures.
(That closes the subject for me here. I have massive technical and medical files on the matter. But back to Anavex.)
Autism Hints, Yes
Might any of the Anavex sigma-1 receptor agonists provide useful therapies for any of the autism spectrum conditions?
There is no way to presently know with any certainty. But there are indications that Anavex molecules may be able to facilitate or promote favorable and normalized nerve connections.
I don’t know if there are murine (rodent) genetic and phenotype analogues of human autism. If there are, I’m certain Anavex scientists have or will be dosing those animals to assess any possible applicability.
This question touches upon the bigger, closely related question: Just what diseases and conditions might Anavex sigma-1 receptor agonists actually treat? Presently, only three are targeted: Alzheimer’s, Parkinson’s, and Rett syndrome. But the pipeline page of the Anavex website shows additional diseases and conditions being considered, for which there are apparently existing lab data. These are shown here:
http://www.anavex.com/pipeline/
But elsewhere heart disease, psychiatric conditions, and others have also been mentioned.
The spectrum of human (and animal) diseases and conditions Anavex Life Science Corp may eventually treat is broad, indeed. The unique and effective mechanisms of action of Anavex drugs, in restoring healthful cellular and organ system homeostasis, are highly suggestive.
Rett Trial Not an Anavex Life Sciences Trial
...it is also a risk! ...one that in IMO could be terminal or near terminal for the company's future.
Further Association Of Insomnia And Dementia
Here’s a report of a study linking increased insomnia and poor sleep quality with the onset of dementia. Better sleep among the aged reduced the incidence and perhaps the severity of senile dementia.
http://www.express.co.uk/life-style/health/844896/Dementia-news-good-night-sleep-disease-research
Ponder the implications of this, should Anavex 2-73 ever be approved for and used as a side-effects free soporific. Sleep problems, common and severe in Alzheimer’s patients, were absent in the Australian trial.
Will Today’s Anavex Cautions Be Voiced Later
This would be an interesting sociological study.
Determine if the skeptical postings appearing here presently and the recent past concerning the safety and efficacy of Anavex 2-73 for Alzheimer’s patients get posted in their near-identical form if and when the drug is FDA-approved and in clinical use for many thousands of Alzheimer’s patients.
In short, will FDA approval thoroughly erase or invalidate the many postings of Anavex skepticism? Will anyone be warning Alzheimer’s patients not to take the drug because FDA approval was based more upon anecdotal accounts of benefit than upon the still-questionable mechanism of action or other spurious data? MMSE and p300 data have already been discounted by some in the early Australian clinical trial. Will similar data plots be equally dismissed in the FDA approval process?
Is Anavex 2-73 a bad equity investment because it necessarily produces poor clinical results among any and all tested or treated populations; or, are the concerns presently only that enough people haven’t used the drug yet to know, for sure, if the stuff works safely and well?
Is it a testing problem, or an innate properties problem?
If the former, will the up-coming Phase 3 double-blind trial be definitive?
If it’s the later, just what are the specific innate problems with the Anavex molecules and their unique, novel mechanisms of action?
Good questions, eh?
Anavex Will Be Bigger Than Presently Envisioned
Would improving/restoring mitochondrial function/homeostasis synergistically benefit antibiotic use?
Maybe we can use a little 2-73 or 3-71 etc and a little less antibiotics in the future...
Come on, it's all placebo stuff!
"PATIENT EVENTS: THERAPEUTIC RESPONSE UNEXPECTED
101001 MORE ALERT REGARDING SURROUNDINGS
101002 FEELS MUCH HAPPIER MAKING JOKES
101003 MUCH HAPPIER WHEN ATTENDING CLINIC APPTS AND ENJOYS MAKING JOKES
AND ENGAGES WELL IN CONVERSATION
101004 BETTER HAND COORDINATION. CALMER AND MORE COMMUNICATIVE
101006 IMPROVING MOODS. READING MORE BOOKS
101007
ABILITY TO PLAY THE PIANO AND READ MUSIC NOTES AT ABOUT 9 MONTHS
INTO TRIAL. SHE USED TO PLAY THE PIANO AT AGE 5 AND LOST HER ABILITY PREALZHEIMER
TRIAL
101010 ABLE TO FOLLOW PLOT WHEN WATCHING MOVIES WHEREAS PREVIOUSLY
COULD NOT
101010 MORE COMPASSION FOR CHILDREN
101011 WIFE THINKS PATIENT IS A BIT MORE CHEERFUL
101013 ABLE TO DO MUCH MORE HOUSEWORK THAN BEFORE
101013 MORE DRIVEN AND UPBEAT LESS ANXIOUS ACCORDING TO CARER
101014
AN INTERNATIONAL ARTIST WHO RESUMED HER PAINTING ABILITIES AND NOW
HAVING AN EXHIBITION IN NOV 2016. WRITTEN A 3 PAGE LETTER TO LONG LOST
BROTHER
101015 PLAYING MORE GOLF NOW BY HIMSELF. MORE CONFIDENT AT GOING OUT BY
HIMSELF
101017 ENJOYED HER TRIP TO BELGIUM - TALKS ABOUT SOME BITS OF HER TRIP
102001 IMPROVED ENGAGEMENT WITH FAMILY/FRIENDS/OUTSIDE WORLD
102008 IMPROVEMENT IN MOOD
102010 FEELING GREAT - IMPROVEMENT IN COGNITION AND MOOD, BALANCE AND
GAIT HAS IMPROVED
103001 PATIENT REMEMBERING SOMETHING HE WOULDN'T HAVE PREVIOUSLY"
Historical Factors At Play
As a biology teacher, I taught the story of the discovery and development of antibiotics, starting, of course, with Fleming’s discovery of the mold Penicillium notatum’s ability to suppress Staphylococcus bacterial cultures on nutrient agar plates. (The species is now known as P. chrysogenum.) This discovery was by propitious happenstance. It occurred because inoculated culture plates had remained un-cleaned for a period, while Fleming was off or doing other things.
Wonderfully, he happened to note Staphylococcus-free zones around the Penicillium growths. Penicillium is a genus of rather common molds. Penicillium spores commonly circulate in the air and drop onto nutrient agar plates, contaminating them. This contamination lead, eventually, to the saving of hundreds of millions of lives — including my mother, a nursing student in WWII. She acquired a bacterial infection that quickly became very serious. The hospital she was being trained at had just received its first shipment of the new penicillin. She was the first there to be given an injected dose, and within a few days of treatment, she was cured. I would never have been without that event (before my birth).
But, as the referenced story states, it was a long and convoluted time and process before penicillin came to the market—for reasons innate to the sociology of modern medicine, and which are still at play with Anavex.
Fleming made his overt, physical discovery of the antibiotic effects of Penicillium chrysogenum in September of 1928. Penicillin didn’t come to practical use until 1942, a 14-year time-to-market period.
Not long after his discovery, Fleming presented a paper, telling of his observations. The professional bacteriology community paid no attention; a mere curiosity of contamination by stray mold spores.
He went on to extract penicillin molecules from the mold, and use them to suppress bacterial infections in mice. He either failed to adequately present this new information to the biology profession, or, they simply paid no attention. Penicillin went virtually un-noticed for a decade. Commercial production didn’t occur until 1941, after intense lab work here in the US, prompted by the onset of WWII. Infected battle wounds are major causes of wartime lethality. Allied use of penicillin was a not-small factor in the war effort.
How does this apply to Anavex’s sigma-1 receptor agonists? We hope, not so much; that a) the molecules would be quickly and accurately recognized as revolutionary medical game-changers (even more so, I contend, than antibiotics in the last century), and b) clinical treatment applications will be forthcoming, treating a diversity of human (and animal?) diseases as soon as possible, without any 14-year lead time.
With the final appearance and availability of penicillin, it quickly came into use. Understandably. Those untreated simply died in a week or so.
But such was not the acceptance of the germ theory itself. Semmelweiss, Pasteur, Lister, et al. showed conclusively that bacteria, “germs,” cause infections. But it took almost a half century for conventional medical science to fully accept the germ theory. Disease was “known” to be caused by bad and re-breathed air, not microscopic organisms in air and water.
In short, medical people have never been quick to re-think what they know and believe about the etiology and treatment of diseases. They know and believe mostly what the medical ancients wrote, and what their med school professors taught, two groups of the most intelligent and knowledgeable humans in all of history.
So, in our case, a team of scientists come along and say (a bit more forcefully than Fleming) that they’ve found a class of novel (new) molecules that restore health to diseased neurons, by formerly unknown mechanisms of action. Of course, the medical community knows better. Alzheimer’s is caused by amyloid and tau protein waste accumulations, and every one of the many attempts to therapeutically clear those has failed. This new Anavex company, we all know, simply can’t have the answer. The known science is better than that.
In the case of penicillin, it was the exigencies of WWII that finally prompted its commercial development and application. In our case, with Anavex, might it be the ever-expanding populations of us Baby Boomers aging into profuse geriatric CNS disease vulnerability?
Goose Pimples Will Give Patients the Willies
One of the greatest concerns and obviating issues of new, powerful drugs are the strong adverse events, side effects that almost universally attend such (but not yet with the Anavex drugs).
The human participants in the Australian early-phase trial did have some side effects. But they were Level 1 and 2, mostly some headaches and upset stomachs, and the like.
Didn't see the goose pimples listed. But, we gotta be real careful. Who knows what debilitating side effects Anavex might be trying to hide from us. They haven't released some other clinical data just yet, so a few here are really concerned.
They can add goose pimples to the reasons data are being withheld.
Right Company, Wrong Commentary
It wouldn’t take much with a browser search, “sig-1, Alzheimer’s,” to come up with Anavex Life Sciences Corp as the company for which someone should fork over two grand to learn about.
But what they would learn is correct as just one point, the company, Anavex. Everything else portrayed about the company is only partially correct, or altogether wrong.
This fellow, the commentator, with only a bit of explanation, lumps Anavex with all the other failed drug companies trying to bring an Alzheimer’s drug to market. He claims, quite correctly, that he has no neurology expertise upon which to base a solid recommendation, for or against, the company.
There are two parties behind this, the guy trying to suck in two-grand subscriptions, and the fellow parsing out just what company the first guy is tantalizing readers about. The first guy wants a bunch of money; the second guy is telling what the company is, and why it probably is not a good investment yet.
Therefore, I see this as but an interesting curiosity. It will generate no significant AVXL sales (if any at all), and will not affect the AVXL share price.
A mere curiosity, of which there are a multitude, of all sorts, regarding Anavex.
Dizziness Would Not Be a Prohibiting Approval Factor
Should anyone think infrequent cases of dizziness by those taking the most concentrated doses of Anavex 2-73 might keep the FDA from approving the drug, take the time tonight to watch not only the evening news on any of the three networks, but watch the many FDA-approved drugs being advertised. Listen carefully, and try to read the fine print at the bottom of the ad frames. You might wonder how these drugs ever got approved.
Almost all of these wonderful drugs can have severe, even lethal side effects. But dizziness is virtually never mentioned as a matter of concern.
The fact of the matter is this. The frequency and severity of adverse events (side effects) in humans taking prescribed doses of Anavex 2-73 are mild and relatively infrequent. They will in no way complicate or prohibit FDA approval of the drug.
It’s a Weigh the Risks Decision
...why isn't Park West or blackrock or the other growing number of large institutions and funds waiting?
But What Could Aricept Users Know
Who, in their right mind, would decide upon the efficacy of Aricept by reading the accounts of Alzheimer’s care givers with experience with the drug?
Check ‘em yourself, if you have the intellectual strength to withstand what you read:
https://www.drugs.com/comments/donepezil/
The real experts are here, on this board (of all places) . They state authoritatively that Aricept is plainly a better sigma-1 receptor agonist than Anavex 2-73, that Anavex 2-73 never has and never will surpass the Alzheimer’s treatment outcomes of Aricept.
Likewise, who would so foolishly entertain the thoughts and expressions of both treated Alzheimer’s patients and their family members down in Australia, after many months on Anavex 2-73. It is known, a priori, that since Aricept never produces such phenomenal treatment outcomes, and that Aricept is a much stronger sigma-1 receptor agonist, those Australian accounts must be simply discarded. Either hopeful thinking (placebo effect), all rare, atypical “super responders,” or a corporate contrivance to fraudulently persuade the public that Anavex 2-73 really works.
Glad that’s all resolved now.
I should sell my small AVXL position and get some Pfizer shares, the owner of Aricept. Think I’ll get greater rewards over there? They have a product of such greater therapeutic strength, as we’ve now learned.