Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Another positive presentation. Now, 2022?
I listened and watched Christopher Missling's presentation. Once again, I searched diligently for any indications that Anavex 2-73 will fail in any of the several clinical trials underway.
Anavex 2-73 (blarcamesine) is targeted at otherwise recalcitrant or un-treatable central nervous system (CNS) diseases. Few systems in the body are more complex, more vulnerable to chemical (pharmaceutical) disruptions. Anyone watching the evening news broadcasts must sit through several minutes (several times) for "advertisements" of various new drugs.
Now, few of those target the CNS; but they do have minutes and paragraphs of stern warnings of all of the side effects that users must be aware of; including side effects that are lethal.
One pair of new cancer treatment drugs are advertised, claiming that users will "have a longer life." Of course, ever try to read the fine print at the bottom of those ads? I got up close to my 50-inch screen to read the lines of fine print. They are only on for an instant, but this pair of new cancer drugs, it was noted, appears to prolong cancer victim lives by about 3 to 5 months (as I recall, maybe less). (What do you suppose the drug costs per month of those 3 to 5 months might be?)
How does all of that relate to Anavex and Missling's presentation? A great deal.
First, before it can be approved and used therapeutically, a new drug — especially targeting the CNS — must show safety. Are the side effects so bad that they negate the positive clinical outcomes? Or, as bad as the side effects are, are the clinical results still so good that the side effects have to be endured?
Lastly, the new drug, simply, has to work. It has to reduce or prevent the targeted disease's bad symptoms to some degree.
Of course, this is why clinical trials are required, a) to reveal the extent of side effects ("adverse events"), and b) to demonstrate useful therapeutic outcomes (symptom suppression or prevention).
Anavex 2-73, once again, wins, on both accounts. No adverse events, side effects, were mentioned in any of the on-going clinical trails — because there are none of any consequence. In every one of the human clinical trials, Anavex 2-73 has been profoundly safe. Rare when treating the CNS. A profound plus.
But, what about efficacy? Are there any clinical data showing efficacy in humans with targeted diseases. Yep; very significant outcomes. Increases in cognition in patients with dementia.
Of course, those data derived from small, initial trials; insufficient in the number of patients and the duration of treatment to yet satisfy the FDA's strict conditions. For me, the keys are these.
Simply, Anavex 2-73 is both safe and efficacious. No disqualifying side effects, but profound clinical outcomes.
All of this will be formally affirmed, later, when the trials conclude. I continue to be confident in the future success of my modest investment in AVXL shares. From my start, several years ago, I could see 2023 to be the first full year when Anavex Life Sciences Corp attains full, successful operation as an expanding revenue-generating pharmaceutical.
I may have been wrong. It might well be in 2022.
Missling, Anavex, and I share interests.
So, I, too, voted for the entirety of the proposals. Dr. Missling, of course, owns a lot more shares than I do, which means he has a proportionately greater interest in getting things right.
Yes, write 'em out at the start.
We got it — significantly!
For a generalized (but applicable) understanding of the significance (good word) of the statistical term "p-value," it is as follows.
Some result appears in a scientific or clinical study. The big question. Was that result actually significant? Did it actually reflect the validity, the truth of the result? Or, were the averaged results of the study merely by random chance, not actually resulting from or being caused by the drug or phenomenon being studied?
P-values are expressed in the following range. A p-value of 1.0 means that in all cases in the study the results were random, not actually caused by the thing being tested. Universally random-chance results. Purely stochastic. On the opposite end, a p-value of 0.00 means that in every case the results were directly caused by the thing being tested, with no random chance variability. Drop a coin from one meter over a desk, and count how many times gravity fails to actually cause the coin to hit the desk. Never, ever, fails. A p-value of 0.00.
Now, rather arbitrarily, "science" has contrived to regard statistical p-values of 0.05 or greater as "lacking statistical significance," meaning that study results with p-values 0.05 or greater should not be regarded as accurate. The results of the study, as good as they might have been, are too likely to have been caused by random chance, not actually by the thing being tested.
Understand, a p-value of 0.05 means a one-in-twenty (5%) chance of random-caused, not actual factor-caused results. If a study fails to stay below this somewhat arbitrary 5% random chance outcome, it's not likely to get published; will never be recognized. Toss the study. It didn't reach "statistical significance," which is a less than a one in twenty chance of random results causation.
Ok, then, the two extremely significant (important) test results of blarcamesine in over 148 weeks of dosing, in people with Alzheimer's disease, measuring the trends of thinking abilities and activities of daily living, were both "good." Well, exceptional — by orders of magnitude. For thinking abilities the p-value was less than 0.0008. For daily living activities the p-value was less than 0.0001.
Simply, there was no chance involvement or causation whatsoever in the phenomenal thinking and daily living results in the 148-week study of blarcamesine in people suffering with Alzheimer's. Plainly, blarcamesine phenomenally suppressed the typical progression of those two untoward symptoms of Alzheimer's.
As the big clinical trial will reveal, when it concludes, we got this.
Missling (Anavex) knows!
How much will I pay, off label?
The early Rett data showed enhanced production of GABA, gamma-aminobutyric acid, which acts as a nerve impulse suppressor. My personal disease, hereditary spastic paraplegia, HSP,(in my particular genotype) has reduced production of GABA in my spinal cord. Consequently, nerves controlling various leg muscles (the adductors in particular) are continually hyperexcited, lacking normal levels of GABA.
There is every good reason to believe, then, that blarcamesine, at some yet to be determined dosage would restore normalized levels of GABA, thereby turning off the pathological hyperexcitability of my affected motor neurons.
So, if I can persuade my neurologist to write an off-label prescription of blarcamesine for my HSP, what might be the range of dosage costs? Certainly, at least at the start (late this year?), my health insurance won't cover that cost. How much might I have to personally lay out for blarcamesine? Any thoughts? (At the time, how many of my AVXL shares might I have to sell to cover this cost?)
Expression of mutations more than mutations themselves.
No idea.
But rats and people have sigma-1 receptors.
No failures yet.
No, a bad, unneeded combo.
Anavex is entirely different; and better
I'm confident.
George, thanks for posting those graphics, telling about the diversity of diseases and conditions blarcamesine may work for, etc.
I just checked, online, my bank account. I personally (dare I say) substantiated, to some degree, my Anavex contentions by digitally instructing my bank to forward to my brokerage a moderate number of dollars. They should be posted and available for new equity purchases on Tuesday.
Now, no one (I hope) is investing in Anavex or any other biotech dollars that can't be lost. Smart retail investors buy stocks with carefully allocated, discretionary dollars, the ones left over after everything else is paid for, accounted for.
What will I be posting should the Rett trial readouts turn out to be less than positive? Or, what will I be doing with my moderate AVXL position?
I'll hold on to it, waiting for the Alzheimer's readouts. Rett and Alzheimer's are, biochemically, very different diseases. I won't be betting my ranch on either disease and blarcamesine. My ranch (well, my house) is paid for. If I'm all wrong about Anavex, my life will go on unaffected.
But I don't think that will be the case. Blarcamesine will change things, for so many. I and my family will benefit, I think.
In the past, something about ice.
Oops.
Well, I take good measures to try to prevent errors in my postings. I fashion myself as an accomplished technical writer, providing useful scientific information to lay audiences.
That takes a good bit of editing; reading and re-writing before posting.
Well, I got too excited in my last posting, the one you just quoted (in blue text).
I claimed that Anavex drugs will be "Even more medically and socially significant than antibiotics in the 2th century."
Should have been "...in the 20th century."
Pretty typical. We know better.
I'm in because blarcamesine works.
I'll be voting to approval all proposals.
I've read the Annual Meeting document with close scrutiny. I find that the interests of the of the listed principals, Dr. Missling, et al.. align very closely with mine. Consequently, I'll be voting for each of the proposals, including the share increase authorization. Missling, Skarpelos, and the others desire to maximize the value of their holdings of AVXL shares. It makes no sense to presume that, somehow, the increase of available shares for the company to sell would jeopardize those values. The value of all of our shares will be protected; even potentially increased by judicious use of the new shares, if or when any of them might ever be issued. (Issuance is NOT mandated by the proposal; only allowed, if and when appropriate.)
"Yea, but wait, if the company sells or distributes those 100,000,000 new shares, that will be a per share value loss of greater than 50%."
No it won't. Missling and his corporate colleagues aren't going to arbitrarily cut the value of their Anavex holdings by a half or more. That makes no sense whatsoever.
Now, given my lack of corporate management expertise, I have no idea just how the additional shares might actually be used to increase eventual share prices for all. But given the described competencies and experiences of the listed executives, from Missling on down, I have no concerns whatsoever. In the Annual Meeting document, there is language touching upon how the additional shares might used. I'm satisfied with those explanations, particularly because we are now at a major Anavex turning point.
In the rest of 2021, Anavex Life Sciences Corp will be in the news, will be increasingly recognized as an important rising new pharmaceutical. In 2022, with the ability to sell blarcamesine probably for at least two medical indications, the company will begin to function as one of the top, major global pharmaceuticals. All AVXL shareholders will benefit, those in management, and those of us here.
Who'da thunk it?
A new study reports why "antibody treatments," targeting amyloid plaques, etc. haven't worked for CNS diseases. Simply, they cause inflammation in the brain. Pretty "adverse."
"Our findings provide a possible explanation for why antibody treatments have not yet succeeded against neurodegenerative diseases," says study co-senior author Stuart Lipton, MD, PhD...."
https://eurekalert.org/pub_releases/2021-03/sri-eaf032621.php
Isn't the "not yet" statement so definitive? No matter, antibody, immunological approaches to Alzheimer's therapy will continue to appear (then fail).
Anavex and Insomnia
Well, a new Anavex patent for Anavex 2-73, now as a treatment for various forms of insomnia; disrupted or disturbed sleep.
http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220210085637%22.PGNR.&OS=DN/20210085637&RS=DN/20210085637
If Anavex 2-73 (blarcamesine) can eventually be used to treat insomnia, what would be the economic impact in the US? Here are some metrics to consider, from an article published back in 2014:
Schwab gives a B, Outperform rating.
Schwab holds all of my AVXL shares. Today, here's their current "rating:"
Current Rating
Schwab Equity Rating: B Outperform
On a scale of A to F.
Blarcamesine and peripheral polyneuropathies.
Anavex things are turning.
Watching Anavex Life Sciences Corp is now getting interesting. I had to check to see when I made my first AVXL purchase; May 2016. I've been following the company closely ever since, perceiving its potential as I incrementally accumulated more shares.
I scrutinized two contrasting bodies of knowledge on the company. First (most significantly) were my detailed readings of the many reports of clinical trials of the Anavex sigma-1 receptor agonist (activator) molecules, in both murines (lab rodents) and in humans. As a biologist I could understand the innate, unique, powerful biology being told about. From the start, I was confident that larger, proper human clinical trials would validate the drugs, which would eventually then gain FDA approval for sales and therapeutic use.
The latter yet awaits, but that will be later in the year when the Rett clinical trial data are released.
Then, the other body of knowledge for me has been that gained by reading the many posts on this message board. A few are easily and usefully dismissed. But most tell something of the diversity of investor perspectives on Anavex. And with those, here is what's turning.
Until recently, a large fraction of AVXL postings, often in the majority, have been quite negative. Anavex naysayings, as it were. These have been by both stock-buying types, and by various professionals of putative scientific understandings. I needn't list out the reasons Anavex was going to be a failure; we've all read them. The molecules didn't and couldn't work like Anavex claimed (or hoped). The diseases the company was targeting, mostly in the central nervous system, simply couldn't be treated by any of the Anavex molecules. Etcetera.
Or, each and all of the Anavex clinical trials had deprecating defects; couldn't possibly produce results that the FDA or other drug regulatory agency could use to approve a new drug. The company was too small for any of this, and had inept leadership. They did everything wrong, it was claimed.
Well, things have changed. The AVXL share price is in the ascent. Postings warning that the mechanisms of action (MOAs) of the Anavex drugs were bogus or impossible no longer appear. An abundance of clinical data has appeared; all of which does support the drugs' sigma-1 receptor activation, with profound consequent therapeutic outcomes. The notions that the Anavex science is inoperable no longer appear. Those questioning the clinical trials have had little to say, realizing that the trials coming to conclusion will yield viable, statistically-significant data; most of which will be very positive.
For Anavex, and longs holding AVXL positions, everything has changed. The only prospects going forward now are positive. The AVXL share price trend will continue to ascend. Ever more external articles and reports on the company and its drugs will appear, favorably telling more of the Anavex story. Then, sometime this year, either in the US with the FDA, or in Australia with the Therapeutic Goods Administration, Anavex will be granted authority to sell blarcamesine. Let the reader ponder what happens then.
Several tears ago, I determined, presumed that my AVXL investments would not be delightfully rewarding until 2023. Things have changed. Things Anavex are going to be very rewarding in 2022; or perhaps even later in 2021. It's been a long wait. But things, indeed, are turning so positively. So fine, for both AVXL shareholders, and for the many patients that Anavex drugs will so successfully treat.
Mention of a new, "undisclosed" rare disease.
I noted in Dr. Missling's presentation the mention of a new, "undisclosed" rare disease in the company's rare disease pipeline, mentioned here:
Well, not only Lily, but me, too.
Thanks for the correction. I didn't see Anavex on the slide (which I had difficulty expanding to read).
--Falconer66a
The new Vivoryon Alzheimer's drug.
I wanted to learn about the new, in-clinical-tests Alzheimer's drug from Vivoryon. The drug, named PQ912, "...is a first-in-class, highly specific and potent small molecule inhibitor of Glutaminyl cyclase (QC, QPCT). In a Phase 1 study in healthy young and elderly volunteers PQ912 showed a good safety and tolerability profile up to the highest dose. A subsequent Phase 2a study (SAPHIR) revealed significant improvements in a cognition parameter after only 3 months of treatment. Based on these findings Vivoryon started in July 2020 a Phase 2b trial (VIVIAD) in Europe in early stage Alzheimer’s disease. A second Phase 2b trial is planned in the US and is supported by a significant grant from the NIH."
https://www.vivoryon.com/pipeline/
Might this new Alzheimer's drug then be a competitor with Anavex's blarcamesine? Once the definitive clinical trials of both drugs are completed, I don't think so.
Like the immunoactive 'mab drugs that have universally failed in treating Alzheimer's, this new drug also targets tau and amyloid protein wastes. But in a different way. Now, there is no doubt that the accumulation of these proteins in nerves and neurons cause Alzheimer's symptoms and are ultimately lethal. But can this new drug, with its unique mechanism of action (MOA) sufficiently stop the production of the waste proteins, or even clear those already aggregated and causing neuron and nerve dysfunctions?
The mechanism of the drug's action is rather cryptically depicted here, slide 9:
https://www.webcast-eqs.com/vivoryon20191017
My impressions are these. The drug very likely will slow, or perhaps for a period even reverse the aggregation, accumulation of the waste proteins in nerves and neurons that cause Alzheimer's symptoms. But several factors need to be quantified in clinical trials.
The first is the trajectory of the waste protein suppression. Will it be linear, progressing to a complete waste protein absence? Or, is the plot non-linear, having reduced waste protein suppression as treatment continues? Inasmuch as the drug apparently does not suppress waste protein production, merely suppresses the accumulation of those wastes, the drug very likely will have to play catch-up further into treatment periods as increasing amounts of protein wastes are generated as Alzheimer's disease advances. Again, clinical trials will determine how this plays out.
Next, there appears to be a dose-related response. Lower dosages fail to adequately suppress waste protein aggregation. It appears that dosages will have to be carefully titrated up to efficacious levels.
At those elevating doses will various adverse events preclude sufficient dosages? Clinical trials will illuminate the question.
Interestingly, dosages of blarcamesine are generally in the 30 to 50mg range. The Vivoryan drug is being administered in 100s of mgs.
Lastly, and actually most importantly, can the Vivoryan drug halt the production of waste proteins altogether, thereby effectively treating (dare we say, cure) Alzheimer's? I see no indication that the drug's MOA could do this.
Now, a comparison of the Vivoryan drug, PQ912, with the Anavex drug, blarcamesine. Not parallel at all.
PQ912 targets the Alzheimer's waste proteins during or after their formation. Blarcamesine, activating the sigma-1 receptor protein, targets the aberrant, pathogenic mechanisms that produce the wastes, in the first place; keeping them from ever being produced. Once again, the "upstream" cellular and process venue.
With that, there is a much-reduced chance that blarcamesine efficacy will taper off at any rapid rate. In fact, blarcamesine may well be continually efficacious, providing with chronic dosing chronic (time-enduring) efficacy. There is little prospect for this with PQ912. Like the other approved Alzheimer's drugs, PQ912 is likely to only slow the lethal progression of the disease. Blarcamesine, on the other hand, has the potential to remove the lethality factor; patients being chronically treated with blarcamesine will die later of some unrelated causes.
Blarcamesine's safety and tolerability are important; allowing long-term, chronic dosing, absent obviating side effects. Let's see in the clinical trials of PQ912 if that is possible with that drug. Presently, that is questionable.
I note that on the Vivoryan website, a good number of other drug companies are graphically listed as being involved in Alzheimer's drug development. All the biggies are shown. But, for whatever reason, not Anavex.
As with all candidate new drugs, run the proper clinical trials, for both PQ912 and blarcamesine, to thoroughly and definitively answer these and all the other questions. On the basis of what I've discovered about both drugs, I won't be adjusting my position in AVXL (Anavex Life Sciences Corp) in any way. I don't anticipate that PQ912 will be a competitor. The "upstream"/"downstream" factors are favorably at play, along with safety and tolerability.
Let the clinical trials conclude.
What is donanwmab's trend and terminus?
Ok, next is ANAVEX1-41.
I read the link and the abstract of the PubMed paper (Sep. 2007), entitled Involvement of the sigma1 (sigma1) receptor in the anti-amnesic, but not antidepressant-like, effects of the aminotetrahydrofuran derivative ANAVEX1-41.
https://pubmed.ncbi.nlm.nih.gov/17641675/
I didn't recall ever checking anything on this molecule. Forgot or didn't know it was on the Anavex shelf. But the paper, telling of a study in mice, told of some rather significant findings, particularly regarding the enhancement or support of memory, working against amnesia. Here's the claim in the paper's abstract:
Conclusions and implications: ANAVEX1-41 is a potent anti-amnesic drug, acting through muscarinic and sigma (1) receptors. The latter component may be involved in the enhancing effects of the drug on long-term memory processes.
Dr. Missling will be telling about the molecule at this online event in September:
https://npd-summit.com/seminar/core-clinical-trial-design-issues-that-prevent-us-from-developing-effective-transformative-drugs/
So, Anavex has yet another sigma-1 receptor agonist, one that enhances memory. Might there be a few applications for that, both in education and training, and in age-related and pathologic amnesia?
Like all the other Anavex drugs, proper clinical trials in humans need to offer their results before FDA approval can be gained. But I've found no Anavex successes in murines (lab rats or mice) that haven't, to some degree, been later validated in humans. There have been no human failures of Anavex drugs that were first studied and validated in murines. ANAVEX1-41 may be the next Anavex success.
It will be interesting to watch what develops with ANAVEX1-41. Dr. Missling apparently has some ideas he wants to share with professional audiences in September.
It's Anavex 1066.
Yes, I made an error in referring to "AV1099." A typo on my part. The profound drug is Anavex 1066. Except for the company's new patent on it, read all about it here:
http://www.anavex.com/wp-content/uploads/AV-1066-poster-November-2016.pdf
My apologies for the error.
Anavex is the real deal, by multiples.
Thanks for posting this AV1066 PDF.
http://www.anavex.com/wp-content/uploads/AV-1066-poster-November-2016.pdf
Ok, once again, the question arises, "Are the therapeutic analgesic results of AV1066 in murines [lab rats or mice] extendable to real humans?"
Of course they are. Mammals have very similar pain biochemistries. Ask any veterinarian if human analgesics work in animals. They do.
But what about safety? Side effects? The authors of the poster made this claim, "AV1066 appears to possess a favorable safety profile."
The favorable results in the study were not stochastic, merely random chance outcomes. P values were all "statistically significant," ranging from from 0.05 to 0.001.
Another Anavex winner, awaiting, now, human trials. I won't be redeeming any of my AVXL shares.
And now, it's analgesia.
Autism applications would be awesome.
I don't think so. No good reason.
Yea, potential hypertensive therapy, too.
Or, before.
Very likely.
Will have to wait.
Consider aspirin's history.