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Thank you, Investor, for this research link.
Also, Merry Christmas to you.
Quote from the link:
Taken together, our
findings support the idea that synaptic dysfunction is different between males and females.
Quotes:
7. CONCLUSION
The overall aim of this thesis was to understand how Sig1R sex-specifically modulates AD
pathology. As the population ages, the number of AD patients, who are mostly women, is expected
to grow exponentially.
…
Our findings support the idea that synaptic plasticity is different
between male and female mice, which may be because of distinct molecular mechanisms.
…
Our data
is also in agreement with the mounting evidence indicating that sex is an important factor in AD
phenotype and severity. “
- from your link
Biostock commentary:
Based on these conclusions, one should surmise that S1r’s should be different between males and females (mice, and if applied to humans…) but should not be widely different between regional groups of males and females across the planet.
In other words, a female S1r is different from a male S1r in susceptibility to AD and treatment activating S1r but females S1r’s would exhibit the deficits to males, mentioned here, consistently throughout the species.
A question arises from this:
What accounts for varying degrees of prevalence of AD within different countries? Should be approx the same worldwide…
Here are a couple of links which I find exciting in exploring the progesterone theory as an explanation for the underlying discrepancy:
JAPAN - Low dementia rate among developed countries:
“Among developed countries, Japan has the lowest prevalence of both dementia in general and Alzheimer's disease in particular.Jun 25, 2014”
https://www.ncbi.nlm.nih.gov › pmc
Global Epidemiology of Dementia: Alzheimer's and Vascular Types - NCBI
“After decades of debate, the pill was finally approved for contraceptive use in Japan in June 1999, 40 years after it was approved in most Western countries. The Japanese Ministry of Health and Welfare had long been reluctant to approve the pill as a contraceptive.May 1, 2001”
https://www.guttmacher.org › psrh
Knowledge of and Attitudes Toward the Pill: Results of a National Survey in Japan ...
“Today various types of birth control in Japan are available to women either in drugstores, online, or through visiting a clinic. About 80 percent of married women in Japan prefer condoms as their choice of birth control.”
https://en.m.wikipedia.org › wiki
Birth control in Japan - Wikipedia
INDIA - Alzheimer’s prevalence:
“And in India, with increased life expectancy and an ageing population, it is estimated that over 5.3 million people live with dementia (a syndrome in which memory, thinking, communication and social abilities deteriorate), of which Alzheimer's is the most common cause.Nov 21, 2020”
https://www.thehindu.com › health
Note: 5.3 million dementia in a country of 1.5 Billion (emphasis)
India and the pill:
https://m.timesofindia.com/the-pill-is-50-but-india-still-undecided/articleshow/5908264.cms
The discrepancy in prevalence among different countries with different policies and cultural practices should, in theory, have no effect on a fixed truth such as: S1r’s differ between males and females.
So, the reason for different rates of AD manifestation across the globe will have me continuing to dig for explanations - and hopefully, scientists will be as curious and excited to uncover what’s behind all of this.
Thanks Inv2014,
Biostock
Nothing better this time of year than:
Bikes
Gingerbread houses
Old mice who are just fine:)
I’m dreaming of a “Pink” Christmas
Listen to those clocks ticking down…!
Merry Christmas, tradherpete and all,
You already know what I think!
Alzheimer’s is a mystery with 2 prominent clues for detectives wishing to solve its “crime” element:
First, there’s physical evidence: the presence of amyloid beta. - That’s like a hammer at the scene of the crime. It’s there but we can’t account for its presence…is it the cause of death, the murder suspect, the murder weapon, or the motive, or just an innocent bystander?
Second, there is this incredible pattern which science doesn’t appear to be including in reasoning the solution to the puzzle/ mystery.
The first thing a detective would do when trying to determine sequence of events at multitudes of “serial kills” (in this case, AD) would be to look for a pattern used by the “killer” or “killers”. Is it random or can we narrow the “suspects” down based on the victims’ circumstances?
Yeah, we’ve been over this before. Whatever causes Alzheimer’s must not only impair brain function (cause of death) but must also have a selection chauvinism for females to the tune of 2:1 when compared to males (gender calibrated at birth, sorry, no identity proclivity games here, can’t fool Mother Nature).
Science/Big Pharma got this wrong for 30 years by looking at the physical finding and trying to pin the blame on it and make it the cause. Bosh!
Detectives and deductive reasoning will get closer: work backwards from the “victims” - MUCH LARGER CLUE than the high drama surrounding amyloid beta…(if Amyloid Beta is the Lee Harvey Oswald of CNS victims, then, Biogen is Jack Ruby, and the FDA and the Alz advocacy groups are the Warren Commission - it’s THAT obvious).
Ask yourself the litmus question when considering cause of disease as a drug-able target for treatment/cure MOA in AD:
Would this account for the gender disparity?
P. Gingivitis and other bacteria would be candidates in my book if the sponsors of the trials testing the drugs which treat these (bacteria/viruses) can show the correlation between females carrying the bacterium/virus (plural, if there are many brain infections causing the inflammation) TWICE as often as their age correlated male counterparts. Everything I have read suggests that women, in general, practice superior dental hygiene to males as a habit. If not superior, at least equal to males, which would give this “suspect” a reasonable/plausible “alibis” for not being the culprit in these serial crimes…we can’t account for them being in 2/3’s of the victims’ mouths/systems at the time when Alzheimer’s begins to develop in brains and that predates the manifestation by decades. Really? An infection taking that long to become virulent?
Contemplate the soundness of the timing…people can have p. Gingivitis throughout life, even young adults/middle age, both genders…why do predominantly old females manifest neuronal death/impairment and dementia at twice the rate of older males after an infection which needed to be increasing plaque buildup for decades?
Get that answer and you get the prize (unless you’re Biogen…in which case the “prize” for discovering the Holy Grail of CNS diseases turned out to be loss of share price, loss of employees (looking at you Sandrock, and coming layoffs), expert neurologists denouncing your drug’s efficacy on the national stage, Congress and Fed govt (US) investigating your approval path, lot of bad press - scandals for FDA - Medicare, Medicaid walking away like it’s a live grenade…hell, even the VA turned this down - someone in Vegas got rich betting AGAINST Biogen. Warren Buffett dumped the stock, Europe and Japan declined (not even politely) and it now looks as though Biogen will NOT be able to carry out the confirmatory ph 4 because they can’t get 1600 participants willing to pay - and that’s at half price.
Yes, LLY is announcing their intent to apply for approval of another plaque remover, as is Roche, but that’s to increase current share price. They have no intention of filing - that’s the second half of the 1-2 punch and is for suckers…it (filing and approval) drains the gains made off the announcement(!) to file)).
You can’t get to dementia from gum disease, sorry CRTX, you’re about to hang an Innocent Man.
As for SAVA’s MOA - filamin A malfunction causing amyloid plaque build up from misfolded proteins, let’s have the gender connection. What causes females to have this expressed at a staggeringly higher rate in old age when compared with males or young folks? I find nothing that can lawfully implicate, let alone convict, the filamin A.
As for the Sigma 1 receptor, we have already discussed the fact that the most potent inhibitor of the S1R, on the planet, is progesterone. Since there is a correlation between females using contraceptive pills (beginning in the 1970’s widespread, so females around age 20 average in 1970’s would now be women in their 70’s) and the current population afflicted with Alzheimer’s. Contraceptive pills contained much higher doses of the hormones when they began (orders of magnitude) versus today’s BCP’s.
Add the correlation between countries who approved use of “the pill” and today’s Alzheimer’s population and one can see a perfect map overlay of where our “killer” was at the time of the crime.
Add in the fact that countries which never approved use of “the pill” have statistically significant lower AD rates today.
Include the knowledge that countries where diets are rich in turmeric (India and Southeast Asia) have lower rates of AD today as well - significant. It’s noted that turmeric inhibits progesterone.
Compounding evidence: Women who have had five or more pregnancies are at increased risk for AD. Fact. But, pregnancies happen when you are young… and progesterone is produced to thicken the uterine lining, endometrium, as a nurturing environment for the embryo to best develop into a fetus.
So, when pregnant, a woman’s progesterone level rises from 1.2 ng/mL to 300+ ng/mL. During the pregnancy, a woman could have her S1r’s inhibited for 9 months. Five or more of these extended periods, where S1r is substantially inhibited, appears to increase the risk of Alzheimer’s later in life. So, shutting down the S1r for extended periods multiple times during childbearing ages can be the culprit at the right place and the right time to create the conditions for proteins to misfold and demonstrate increased cognitive impairment later.
That’s not just a random pile of facts or coincidences and it’s certainly not magic or conspiracy. But, it does help explain a correlation between the S1r and the gender difference of Alzheimer’s population we see right now.
Then, turn your attention to chromatin and look for gender discrimination there. Outta time for now - you got this!
Can’t promise that S1r agonists will cure AD but if so, the gender “mystery” will have been solved (to my satisfaction). With other treatments - just not seein’ it.
Healthy, happy, prosperous, 2022 to all.
Wish that Benny were here to usher in a new year with us.
A 12/31 11pm toast to the AVXL demons, rascals, and merry makers - aces, all! will be offered and in memory of those we lost.
Raise a glass wherever you are in solidarity:)
And, at midnight, drink to those whose afflictions might see some relief in the coming year(s) as soon as possible
2022 - a better year for all, I hope
Cheers!
Biostock
PS: FTR, I know, it’s not a crime scene nor detective series, and they are all just biotechs doing trials and trying to develop drugs which pass trials which is a tricky business (got that tattooed) and promise I will be very careful, once and F’r All!:)
If the dosage of A2-73 presents “tricky navigating” and has the potential to “trigger” an “anti-effect” beyond certain threshold, etc. etc. etc., recall that Anavex has a patent for an intermittent dosage scheme pertinent to A2-73.
The fact that the dose is a single strength in the AVATAR study (versus placebo) and that the dose has not been disclosed (other than higher than US trial dose) should have invited questions regarding the possibility that it is being administered intermittently.
Dr. Missling stated on the latest cc for the company that the US trial for Rett administered “A2-73 low dose once daily to patients”. He made no similar statement (once daily) when referring to AVATAR, although he mentioned it was a higher undisclosed dose.
If there is intermittent dosing going on with our drug, for any or all indications, now(!) would be a good time to elucidate any potential drawbacks to daily high doses - before releasing the results which may include an intermittent regimen.
In the interest of this investment, pertaining to IP longer term, it’s fair to note that a manufacturer can produce a generic once the drug is off-patent but they cannot infringe on your use of intermittent dosing which would be in effect and prove advantageous thus making genetics unusable beyond the threshold of drawback.
Good luck to all
Hail 2 Pitt!! ACC Champ contenders kick off 8pm EST, shout out to Pickett!
H2P!,
Biostock
“2-73 and 3-71 come at it (AD) from different angles and could be complimentary…” (paraphrase)
That’s what I heard Dr Missling say on the cc.
I did not put this up as a possibility, the CEO did. He never mentioned a combo drug - just trials which include both drugs separately. (Relisten to the call?)
I simply pointed out that such a prescription regimen would double the AD market.
You suggest we won’t go down that route, but our CEO said this recently this afternoon. Time will tell.
Have a good holiday /
Bio
The possible combination of 2-73 with 3-71 doubles the market for AD for Anavex and some partner.
Used to think in terms of one drug supplanting another - doubling is a very powerful metric in a market with NO efficacious drugs.
Nidan,
Don’t spool up over this. Study the board!
Keep calm - check
Return fire - how’s this?:
The House and senate will now hold investigational hearings. (Very publicly, whether kabuki theater or not. They need to be seen “acting busy” doing the work “of the people, by the people, for the people”).
I disagree that nothing will change. One thing is certain - Biogen’s approved Aduhelm was sent up as a proxy/ sacrificial lamb to put the actions of our fearless leaders in the limelight.
Ok, so they kill exactly ONE very controversial drug on their watch on behalf of the citizenry - Aduhelm. They will discuss the ineffective nature of the amyloid drugs in treating impaired cognition and rendering their surrogate endpoint not of clinical benefit.
Ok, watch this next move - will not take long AT ALL:
If Dr Missling has ever even so much as looked at a chess board in his life, he should do (already initiated) an interim look into the AD patients.
Release those results DURING the hearings.
Include a price estimate below $15k per patient (based on Bourbon’s work up, or just under $10k per patient from George’s estimates) in the PR along with superior efficacy and no harmful effects.
Not many things will feel quite as good as landing the one, two punch of: killing amyloid theory (cutting Biogen to its knees along with clear message to all of the “me too” drugs) and having our company’s name and MOA bandied about on the floors of Congress. Can you say instant price per share explosion (without approval needed?) and interest from plural white knights?
That approval was too blatant and too controversial to be real. Was a poorly disguised head fake to move the political football to price gouging and make FDA/BP’s villains and politicians heroes.
C’mon, such a move was more than meets the eye. It insisted upon itself.
This has turned around in less than 3 weeks from the whistle. In the beltway? Seriously?
Dado - great call, you were on the right side of history. Look at the chess board. The Adu theory is in full swing.
If the second quarter deadline is missed, it will be because the goods SHOULD be released during the hearings, imo.
Our stock price will increase as Senators/Congressional Reps mention “other drugs which may be more effective and cost less” (the entire biotech sector AD space will ignite, as it should). If companies are mentioned by name, we will fare very well (even if they only use SAVA and ANVS as examples - but if interim results are released simultaneously, the media will have to wag tongues).
Keep calm, return fire.
As to the Chantix scandal now hitting the FDA (curious timing, lol), I mentioned that after the FDA statement that other drugs have been approved with worse data, we should all run to our medicine cabinets to see what we have been taking.
Could this have only referred to oncologics approved through accelerated approval (not blockbuster sales drugs for something as common as antidepressant and smoking cessation)? The Chantix announcement makes that unlikely.
Watch that chess board, players. We sure wouldn’t want to wreck our new bikes -
Have a beautiful summer weekend!
Biostock
Nidan,
Don’t spool up over this. Study the board!
Keep calm - check
Return fire - how’s this?:
The House and senate will now hold investigational hearings. (Very publicly, whether kabuki theater or not. They need to be seen “acting busy” doing the work “of the people, by the people, for the people”).
I disagree that nothing will change. One thing is certain - Biogen’s approved Aduhelm was sent up as a proxy/ sacrificial lamb to put the actions of our fearless leaders in the limelight.
Ok, so they kill exactly ONE very controversial drug on their watch on behalf of the citizenry - Aduhelm. They will discuss the ineffective nature of the amyloid drugs in treating impaired cognition and rendering their surrogate endpoint not of clinical benefit.
Ok, watch this next move - will not take long AT ALL:
If Dr Missling has ever even so much as looked at a chess board in his life, he should do (already initiated) an interim look into the AD patients.
Release those results DURING the hearings.
Include a price estimate below $15k per patient (based on Bourbon’s work up, or just under $10k per patient from George’s estimates) in the PR along with superior efficacy and no harmful effects.
Not many things will feel quite as good as landing the one, two punch of: killing amyloid theory (cutting Biogen to its knees along with clear message to all of the “me too” drugs) and having our company’s name and MOA bandied about on the floors of Congress. Can you say instant price per share explosion (without approval needed?) and interest from plural white knights?
I really wasn’t typing to “hear” myself type. I have better things to do - this is the play.
Watch things play out.
That approval was too blatant and too controversial to be real. Was a poorly disguised head fake to move the political football to price gouging and make FDA/BP’s villains and politicians heroes.
C’mon, such a move was more than meets the eye. It insisted upon itself.
This has turned around in less than 3 weeks from the whistle. In the beltway? Seriously?
Dado - great call, you were on the right side of history. We see the board. The Adu theory is in full swing.
If the second quarter deadline is missed, it will be because the goods SHOULD be released during the hearings, imo.
Please, investors - wake up and see this move. I know the theory sounded unbelievable. Do you see it now?
Our stock price will increase as Senators/Congressional Reps mention “other drugs which may be more effective and cost less” (the entire biotech sector AD space will ignite, as it should). If companies are mentioned by name, we will fare very well (even if they only use SAVA and ANVS as examples - but if interim results are released simultaneously, the media will have to wag tongues).
Keep calm, return fire.
As to the Chantix scandal now hitting the FDA (curious timing, lol), I mentioned that after the FDA statement that other drugs have been approved with worse data, we should all run to our medicine cabinets to see what we have been taking.
I was assured that:
This only referred to oncologics approved through accelerated approval (not blockbuster sales drugs for something as common as antidepressant and smoking cessation). Well, this announcement was the pawn guarding my piece. The oncology defense was a blunder in hindsight.
Watch that board, players. We sure wouldn’t want to wreck our new bikes -
Have a beautiful summer weekend!
Biostock
The pull effect from duped patients and families might be a factor.
But, as to Corruption has no boundaries, same applies to lawyers*
*(No offense to any lawyers present)
Med mal waiting in the wings…they already have expert witnesses who have stated this drug is not statistically effective nor safe. Easy cases - lot of press and money. I feel sorry for the families/patients but I believe most will be VA victims.
Of course there are more ripples to come - this is a huge hot button topic now and probably much longer to come.
We should fare well.
ATH,
I’d like to see a BANNED IN AUSTRALIA label hit the press in this pile on re Aduhelm’s media attention.
If other countries step up…I’ll buy the drinks!
Nice,
Bio
I agree Steady.
Was just pointing out that we are in fact associated with the Holy Grail preferred dogma of anti-amyloid - just upstream.
The FDA could sell that or buy that if needed to save it’s ass.
But, in effect, it would be riding 2 horses at once for awhile as we would still be acknowledging the amyloid plaque theory as the root until a crossover can be published extensively discussing that people walk around with plaque and have no dementia and the clearing doesn’t restore cognitive function on its own so - zero correlation.
Thanks for adding to the discussions always /
Bio
Power,
Excellent post (even in light of our different views!)
I believe that the FDA has put there foot in it with this decision and the media and advocacy backlash. Now, add in Congress, Medicare, private insurance companies and prescribing doctors.
I believe that our biomarker will be a guarded move on the board even though it is not purely amyloid clearing. Please don’t forget our drug is amyloid preventing(!) upstream.
The FDA could pivot from amyloid clearing to amyloid prevention on a dime if outpouring of heat.
That’s our pawn guarding the move: the press, advocacy groups, doctors, payers.
We can take our finger off the piece, imo.
Thanks for your valuable contributions always, especially regarding Benny recently. He’s still with us on this journey.
Peace,
Bio
Agree raja,
It (Au early enrollment completed) was the threat which had the FDA pinned into having to make a blunder move.
Australia forced the unpin. It’s all in the big post and I commend the plan (no trials in US and give Adu et al enough time to be completely written off before we gain the space. Timing right and 2 pawns to the wall precede with at least one giving us revenues to sustain).
You got it. Indeed, Rip Van Winkles must be awakened - napping for too long.
Well done, thanks,
Bio
That’s the ticket!
It’s not what you don’t know that gets you - it’s what you know for certain that just ain’t so
That’s wisdom, Red.
Thanks, Tom.
Here’s what Congress will be saying to FDA and BP via the hearings and subsequent enactions:
58% of physicians say they will not prescribe Aduhelm.
(Ditto dado’s info from the front lines)
The ball has moved over to Congress. Read what will be discussed in the hearings: clinical effectiveness tied to drug pricing. Ask: does this help or hurt Anavex, if it becomes policy??? Helps us/ hurts every other company out for a quick SP boost with talk of submitting BLA. Most will wait until after hearings and not even submit - it’s a spotlight pump (never let a controversy go to waste).
https://endpts.com/senators-call-for-hearing-to-examine-how-medicare-will-handle-biogens-new-alzheimers-drug/
Here’s Lilly latest:
https://www.google.com/amp/s/seekingalpha.com/amp/news/3709766-mizuho-enthusiasm-for-eli-lilly-alzheimers-drug-tempered-after-talk-with-company
Not sure they will submit; not yet aligned with FDA.
This is all just in one day. They are riding BIIB’s coattails for quick SP boosts…window dressing for 2Q?
What will be left after the dust settles? Sadly, the VA is a captive audience and they will serve their country once again as they are put on the “token” approved med to be sacrificed at the altar of amyloid failure. Medicare will pay the minimum and the most vulnerable (of the approved subset of “clinical effectiveness” as determined by Congress(!!!!!!??? ) will be the new thalidomide generation. Babies and old folks.
We could not have gotten to the point of hearings without the approval(s). Now, laws can be enacted to stop price gouging for very bad medicine. That’s a needed thing.
When Janet Woodcock stated that drugs have been approved based upon less statistical ground than Aduhelm - how many of you ran to your medicine cabinets? We don’t know what(!) we have been taking. And that’s straight from the horse’s mouth. Scary as heck. Have to fix this.
Perhaps, the FDA will reveal how many disaster drugs there really are now that we have a drug which could improve many areas safely.
In chess, sometimes a move which looks like a capture is a trap. Keep an eye out for those, doesn’t become obvious until rear view applied.
Meanwhile,for Anavex, appropriately priced, effective drugs should fear not the coming of morning - we are not marked to die in this battle. The day is ours.
Thanks for remarks and input, dado. Just a matter of time/patience and the knowledge of what we have.
Watch this develop.
Biostock
Boopka,
My gut feeling is that Anavex will test the waters of AA with Rett first (as stated in the PR of meaningful clinical outcomes.) No surprise there.
If that flies…I would do the interim AD and stay afloat (well!) with Rett revenues until the AD trial completes. By that time (48 wks), Adu will have had enough rope to be frowned upon and other competitors will not be as advanced as we.
But, if Adu is clearing a path for us, as Bourbon suggests, let them get the acceptable price range and sticker shock flak, and the nasty side effects, etc.
I think we go for the full completed ph3 trial with biomarker and endpoints stat sig and apply for AA. If Adu is leaving a void, we should have favorable pressure after success in Rett and interim look…should be a putt. Also, our sigma one receptor MOA should have gained wider acceptance against a cause of AD as opposed to symptoms. Baby steps to get the new order widely accepted.
A year to get on the green and let dogma get off the green (penalty strokes…just put them down for max on that hole.)
That’s AD. If Rett doesn’t fly with FDA AA, as Missling - I go directly to AU for SAS use and approval.
GLTU / valuable input always,
Bio
Nice reference, Talon.
We gotta pressure cooker going here but my money is on the one who developed the most pieces and has taken away so much real estate from the opponent, Anavex.
Thanks to moves such as castling, and occupying a lot of squares, Biogen had very few open squares left. We truly outflanked them.
The queen advantage they enjoy at present will be short lived. The gambits worked snd will own the day.
Thank you Talon - an officer and a grand master!
Bio
Tradeher,
Yes, that was a great post - you were correct and timely.
I think Dr Missling had enough time to think about the impending decision but there was more to this entire set up than meets the eye.
Missling could not have maneuvered the overseas trials at the point in time when Biogen submitted their BLA. That would have been impossible.
The likely explanation is that he has been aware of the hegemony in the AD space since he came on board Anavex and before. He knew the need for end runs, sweep arounds, gadget plays, and audibles from the beginning.
He knew how many people saw our little posters at the big conferences and how few audience attended the oral presentations. This awareness led him to take detours and alternate routes.
I give him credit because as you state the odds on favorite was dogma. He had to device a way to beat the house (nobody beats the house), or fight City Hall, or, as you put it - play the away game. We were on their turf.
That makes his moves more impressive because they were disciplined and shrewd (everything from the hires chosen to the neutral turf for the trials). He took heat but he proved right (so far).
It takes fortitude to play small ball. Manufacture each run (no big hitters - war chest like BP, heck that’s easy…an idiot’s job). We had to raise funds creatively through partnerships and endure neglect from press and small venues and so forth.
He understood what he was up against further back than most here.
Consider also that the FDA might have gotten a little tired of doing BP’s dirty work. Every time a BP said “Crap”, the FDA started grunting. Perhaps, there was a bit of liberation in their decision to pull the curtain back?
We may never know what finally influenced them to approve Adu. I just maintain that if this were business as usual they would have done it much more secretively (at least gotten some of the Ad Comm members to give a thumbs up). The blatant aspect is my point of incredulity. Especially, knowing this would dominate the media and leave a mark. They did it anyway. That just isn’t how corruption works. And, again, it could have been down prior to this if they were in the tank for dogma.
Thanks for ALL you great posts / not just that one / you rock!
Fog lifting…let’s pronounce Adu approval a good thing (like sliced bread).
- Bio
GL, Steady.
I should say so…if another shoe drops in the data rich quarter - you should be looking at…Daddy needs a new pair of shoes…lucky dice:)
For the sake of all, we hope you get a nice spiffy pair!
C’mon lucky 7! (not SP…craps!! Lol)
I believe that is his intent - which is a strategy in the “good to best” range.
Nice call, boi. Let’s hope these dominoes where were carefully lined up fall neatly and…soon? :)
Bio
Investor,
I was not following the rare disease non approval, however, I would consider whether any sort of dogma had controlled that space for eons. My bet is - no. And then, too, consider the economic burden which the disease presents. If small, well, squeaky wheels get grease.
Finally, the FDA makes edgy calls both ways, imo (and with context unknown - corruption? Incompetence? No idea really). But, if a company knows that’s how the game is played, they become aware that you must put the proverbial gun to the head to succeed. Australia nearing a possible provisional approval was our proverbial gun.
I never thought you were motivated by a partial investment loss in questioning the decision. I know that you are a top notch investor who is keenly aware of the DD on your portfolio. Credit to you!
I can just say that if extraordinary measures are required, a company needs to be aware and act accordingly which I see that we did.
GLTU (your posts are brave as a skeptic, but respected as such - thanks)
Bio
In a post prior to the Adu approval, I stated that the interim results only require a nod from Missling. He was non-committal when answering questions regarding whether we would or would not take that step.
I mentioned that if Adu were approved and I were Missling, I would NOD!
He should NOD.)
GLTU/A
Bio
Agree, Jon.
A threat can come from a pawn and be effective on a higher piece. It only needs to be in place.
Regarding the effectiveness of the threat:
Not a day goes by without dismal press for Biogen/Adu. Continued calls for this to be axed from every stakeholder in the chain. They are blockaded and will be fortunate to escape with any semblance of a reputation or market share.
Meanwhile, Anavex is getting positive press almost daily in equal proportion. And, I believe that is no accident. The pivot has to swift and aggressive to be permanent. Old science has to give way to understanding of new science. I believe that is happening swiftly.
If you can believe your eyes, believe that what is taking place is a real paradigm shift in Alzheimer’s space and CNS. We are at the epicenter of that shift.
Even the FDA made it part of the official approval announcement that this should open the door to new theories and approaches to treating this disease as various drug candidates are progressing.
Thanks for the opportunity to share this continued confidence in our plan for success. Let’s let the moves play out. GLTU
- Bio
Bourbon,
Reread my hypothesis.
The chess references are probably obscure I’ll admit, however, the FDA had no choice…Missling “pinned” them with his move to Australia. With the threat of Australia, the FDA had to kill Adu by approving. If they had denied approval, then they would never have been able to approve A2-73 without additional trials.
It really was a two step process. We activated the process for approval based on a single trial via Adu, then watch them die by a thousand cuts and we advance our queen. Mate.
My written piece might not have been as well understood as sports analogies but this was a pin - zero choice. And Missling was ready with the appropriate moves. He played it like a master.
Thanks for opening up this discussion for the additional clarification. You are astute! We all see it now. This should be book moves (especially with our pawns to the wall) Mate.
Thanks Bourbon - valuable!
Biostock
infitvest,
Not being stingy with the targets/nuggets -
It would not benefit anyone giving or receiving the nugget information as the knowledge of upcoming “giraffe and a half graphs” coupled with resulting activity (human behavior algo) would invalidate the projected outcome.
I think Heisenberg has been discussed.
Having said that, I will add that we have no interest in stocks without flashover potential and we are holding Anavex as well as guarding the projected price target from disclosure (so as not to change a thing!)
Draw your own conclusions. This compromises nothing -
Wishing all investors bountiful days,
Biostock
Sokol,
Thank you for these follow on comments - spot on, imo.
For clarification, I never suggested that the FDA acted selflessly, only that they were now able to capitalize on the “bribe money” or “pay offs” or “kick backs” which they never succumbed to with any of the previous plaque attack drugs.
I believe that I specifically stated that the FDA was now free to get their “take” for approving a reprehensible drug as long as they did it out in the open to demonstrate the wholesale graft and rule bending that it would take - regardless of how unseemly, simply because they knew that another drug and possibly others will follow which actually have merit in the fight against Alz. The game board is open for all the useful drugs which may come along as the old guard will not be heard from again.
I believe that was misconstrued due to lack of sufficient assiduity in keeping one’s eye on the ball.
…and in that sleep of death what dreams may come, ay, there’s the rub…
I think the rub came from “dreams” of what I postulated, as opposed to reality.
Equal esteem for the insightful posts you always contribute - thank you for your time.
Bio
Respectfully,
Kowtowing to lobbyists is usually considered scandalous and shameful and those things are done with as little fanfare as possible.
This was done akin to the Macy’s Day Parade…
How do you reconcile that? The blatant aspect -
Thanks I’m advance,
Bio
I had considered all angles. If this were continued hegemony, my Occam’s razor says it would have been done in a different time slot.
Occam's razor can have serious consequences as it can lack firmness and consistency when applied to complex ideas or phenomena, Occam's razor is more commonly seen as a guiding heuristic than as a principle of absolute truth.
This was a complex real life situation. Occam’s razor does not apply to dismantling unexploded live bombs - the more obvious of the two wires should be cut? Seriously?
The Adu Post
Why this happened;
Dogma (never have used the word cabal). Dogma is simply one track thinking which is relentless and obsessive in nature which when coupled with power (people who control committees, boards, publications, teaching) pins itself to certain ideas and fosters nothing but those in an irrational fashion. It is insidious, intolerant/dismissive of new approaches, and continues to teach and indoctrinate successive generations (like the monkey banana experiment) until no new thoughts are developed/conceived/permitted to be brought forward. This is dogma and when it enters an environment it is like a parasite which envelops a host - no cell left unoccupied and nothing new can grow as long as dogma stands (political scientific investment/business whichever arena). Dogma never dies, it must be killed.
The notion that the FDA is corrupt and would be bought/paid off in order to approve this drug is the group of moves which in chess are referred to as The Scholar’s Mate: 4 move checkmate. This (Adu approval) was no Scholar’s Mate. Here’s the compelling reasoning why that’s not a logical explanation: since when has any BP NOT possessed the resources necessary to buy the FDA? They could have coughed up 200k$ going as far back as the first amyloid plaque mab if that were the necessity.
Ask yourself why the FDA could approve a completely failed drug in such a blatant open reprehensible way now, today, as opposed to former days in the life of the amyloid theory when the prevailing winds were more favorable?
In order to kill dogma there must be a successor which is not part of the dogma. In the dynasties, it’s “meet the new boss, same as the old boss” (credit, The Who). Kim Jong Un…not unlike all the “Kim’s” before him. Nor will the next one be. Much like the Caesars - it’s simply a new name to learn but the dogma remains (Just Around The Corner Came Nero: Julius/Augustus/Tiberius/Caligula/Claudius/Nero - your mnemonic for the day).
If the FDA approved the dogma prior to Adu, or not, every drug which came after would have to have been a plaque mab. The end of civilized medicine for Alz as we know it.
Why could they take the bribe money this time? When they could never quite bring themselves to take it before??? Scruples? No. Valid evidence? F No!
Because they now have an heir apparent waiting in the wings which represents a new regime? Hell Yeah!
And now dogma must die. But how do you kill it?
Expose it. Exposure kills dogma like light drives away cockroaches. Someone has to expose it and show people that it is a failed theory so that it can be seen for the repulsive instrument it has been all these many years.
In broad daylight, run it up the flagpole where it will be saluted or refuted. Look at the renowned credentialed professionals coming from all directions to refute this. It’s over. The theory is only spoken of as non-efficacious, serious side effects, expensive and unconscionable.
Exposure. It’s why Mamie Till left the casket open. People would forever say that racial bias was “just a fantasy” and “a bogeyman” and “all in your head” if they never saw it with their own eyes. The body of a disfigured youth, not even recognizable, deprived of life, had to be seen to be believed. It was.
Saddam Hussein, had to be seen dead. Mussolini was dragged through the streets. Announcers had to intone, Elvis has just left the building. Some people thought Elvis, Michael Jackson, Princess Diana, were still alive in hiding somewhere. The human mind needs a free body or a trial to detain/imprison that body if grounds are found (habeas corpus let us have the body - until proven guilty - the cornerstone of our legal system down from Rome - Latin phrase). Tell a person there are billions of stars in the sky and they’ll believe you. Tell him a bench has just been painted and he has to touch it to make sure.
The concept of amyloid plaque was intangible, as the stars in the sky. The trials are real, as the bench. Folks must see this theory die tangibly before they will accept the death knell.
Once the dogma has been cleared, it opens the chess board for other players and pawns (theories) to advance and attack the REAL target. The target has never been Biogen, BP, FDA, or Amyloid theory. The enemy has always been Alzheimer’s - that’s the king, overshadowed by the queen (incorrect amyloid theory causal connection) all these years.
The FDA did what Bobby Fischer did when he was 13 years old and playing a grand master in the match of the century. He made the sacrifice of the century: sacrifice queen. Not exchange queens, or trade for a lower piece, he gave up his queen. Why? To checkmate the king.
FDA finally saw that it had to play the hand up/open and show this theory to the world. If it took graft and complete rule breaking to “approve it”, and that is known, and more media expose how poor a choice this was / worst in recent history…etc, and if the drug is monitored closely and can be revoked, other theories can come to light.
Anavex filled that void instantly after approval was condemned and sank in. Our MOA has now stepped up. There’s an order to how the pieces must fall. We are employing the correct order to effect a strategic outcome - dictator regimes don’t just tumble themselves, you know.
The transition must be swift and permanent.
Pawns to the wall: Rett and PDD equals 2 queens and new regime ushered in along with the peer reviewed article.
If Adu had not been approved (to fail) it could never have set up for an Anavex move forward on the board. Gained real estate and very soon material (pieces i.e., $$) Along with control of the strategic center squares and tempo; recipe for the win. If Adu had not been approved, more plaque drugs would have kept advancing. It’s done. It will toll its own bell.
Interesting things to think about:
Dr Missling said we have had interest from other companies but he wants to maximize shareholder profit.
In chess and business, the plays which end the game and determine the winner/outcome are:
When you sense you may be in danger of losing but not sure, you offer the opponent a draw. If he/she accepts the draw, they weren’t confident of the outcome either - draw. Fair.
If he/she does NOT accept the draw, she is confident of the outcome (which you both should see) and you resign. That’s the honorable play. The exception is in the case of a young prodigy who has played brilliantly and is close to mate - you do not offer a draw, instead, you play to mate and allow them the full victory, not a resignation. That’s chess protocol - show posterity the progress of play down to the victorious Mate.
If Missling is not quite sure how our human trials will turn out, he must shake hands and accept that draw (offers which he has mentioned). If no offers are made, he must resign. Since he did neither he is confident that he sees a clear path to mate.
That’s good enough for me, though I intend to watch. This is the dawning of a new age. ( Cue: Theme from 2001 A Space Odyssey)
Elvis left the building on June 7, 2021.
The sigma 1 receptor MOA which is used by Anavex states, among other things, that as we age expression of the S1r is decreased. And more so in AD patients. Although it is not necessary for approval, I would feel more comfortable if our MOA could account for the gender difference in the disease. That would tie this up with a neat little bow and in fact it should be accounted for in there somewhere to make the case not simply compelling (folks respond so that’s the aim) but airtight.
Let’s see what the age factor looks like:
US female population is slightly larger than male to begin with (more girl babies born than boys - Dado is an outlier - all boys, 3 - as am I 2-1).
The Vietnam war killed 53,000 young male US military soldiers in combat, 17,873 non-combat, and 159,000 wounded according to US VA statistics. Additionally, it is postulated that later war casualties from various non-combat related issues, as well as PTSD and suicides, substance abuse casualties could have put that number closer to 2 M veterans dying from war related causes.
That was an event 55-60 years ago which decimated (literally reduce by one-tenth) the male population which would be facing AD due to age related loss of S1r decrease about a decade ago and continuing.
We only need to add the average life expectancy for females slightly higher than males (now that childbirth is no longer a young female population thinner and war still claims young males), as well as the Progesterone Theory (copyright Biostockclub) to account for the AD female chauvinism. The MOA was compelling and my theory provides further evidence of it being related to the cause. That’s why I brought that piece into play early in the game - still standing and defending. If it helps the cause at the end - just recall I planned that move in 2018. We will get this!
Additionally, BIIB has 9 years to prove efficacy/clear safety over and above everything else. Our IP patent on AD expires 2030 (I believe) which is 2021 plus 9. Hm. If we are stalled and forced to perform another big trial or 2 big ones…IP expires…Biogen et al can use our formula for AD - how about that Morphy Defense as a reply? But, with Rett and PD pawns almost to the wall and other interested BP’s we will not let this slide, chance of that happening: very slim.
The reason this happened is because
one can’t prove a negative. If Amyloid theory is never tried it can NEVER fail…trade off - must fail the negative first (amyloid/Aduhelm) in order to open up the board for new theories which will be effective.
Today: further confirmation - Public Citizen calling for FDA heads to step down or be removed.
In either case of the Adu decision, Anavex had the FDA pinned (chess, immobilize a player pinning it between king and threat of check) with threat of TGA P4 approval. Had to move a “pawn” in between to unpin the threat of check. I believe the offering up of the amyloid theory by approving in order to kill it was the sacrifice FDA made in order to have Anavex approved for Rett in US followed by accelerated approval for AD - since that “trade route” has been pioneered by the soon-to-be-revoked Aduhelm. I hasten to add: with very different press coverage surrounding this one and Ad Comm unanimous support. Throw in the advocacy groups and you’ve got a winner out of this gambit - worth all the preceding moves.
If denied accelerated approval, we have Australia ready and waiting with the SAS provision to demonstrate the side by side (Pepsi challenge) between Adu and Blarc. The walking dead vs the Waking dead - no contest. I discussed this clear and apparent showdown in a post prior to the Adu approval. Lot of moves on the board. We still control the center and have plenty of real estate and material guarded (patents) to see the opponent concede…it’s THAT obvious.
Don’t let me ever tell you there’s no chess game going on. Each decision every day of your life involves some form of strategy (think: crossing the street, random walk or timed maneuver? Anyone over age 9, unaccompanied, who doesn’t employ the “right moves” will not go long.)
I know of some fairly quick studies who still fall for the Scholar’s Mate e-v-e-r-y d-a-y o-f t-h-e w-e-e-k - that’s WEAK.
At least learn to Think about bigger vision than tunnel vision if you are looking to get wealthy, healthy, live well and long. The 4 move trap belongs to lower echelon evolutionary species. Not mammalian brain - can’t see beyond “broad generalizations” e.g. “horoscopes are for housewives”. Taunis, I’m a Leo and my horoscope every single day says: This is your f’in day! I stand with you in not tolerating gender discrimination. (Most men feel the same, imo.)
Use your cerebral brain to ask more questions: why would the FDA halt trading at 10am (bicoastal attention) to announce the most blatant ass-chap decision in my lifetime when they could have done it after hours? Why? Seems kind of next level attention grabbing shit, no? If it’s a scandal, it’s usually done in the dark. Not a scandal/corruption/broken system. The fix was in - this WAS the FIX for the broken system. The only way to fix it. Don’t stand under a heavy branch which is half broken / far less dangerous to saw it off. Saw it off! Now, it poses least danger and a new one will grow.
So, they disagreed with and lied to an advisory committee. They disregarded statistical measures of clinical benefit (set by them), shifted endpoints after assuring they would not, acknowledged serious side effects but weighed the (non) benefit and found it ok if kept under further monitor, and now face backlash about resignations, payoffs/contributions/bad press - get that exposure!/ calls for more heads to roll, in broad daylight, market hours, all eyes focused… recall when the discussion was about black swan events? This is a magnificent black swan - it is never seen. There is a reason. White swan (queen, well Knight(!) making an appearance soon)
There was a reason I saw the SAS move in September as well as the 1.5B$ MC by June.
It pays to think ahead - never be afraid to do that - it is not a daydream or fantasy (if so, why are my daydreams coming true? And I’m about to step up my fantasies…)
Dr. Missling is a dreamer who can execute the dreams of checkmate by making the rational, clever moves he has been making, at the correct time and backed by legitimate science. I’ll wager my AVXL balance that he would not be taken in by the Fool’s Mate. Neither did any of you wayyy back when we were at 1.95/sh and I quoted W. Churchill that This was our finest hour. For those who held…it was. Thanks to that endurance, we have today. And shout out to Bennyboy wherever he is. (Personal note: I prayed for him at a grotto yesterday and a butterfly landed on my shoulder. Take that for what it’s worth.)
This was no Scholar’s Mate - this was Ruy Lopez open, Morphy defense reply, Marshall Attack…wayward queen response…she’s a rogue of mayhem (past 30 years…the devastation in CNS…lost real estate/material (captured pieces)/ but the kiddie-counter defense works on wayward queen and she is eventually captured.
You have all heard the expression not to pay for the same ground twice when doing work. Don’t move things which will have to be moved again - just move it once to the final destination. The FDA has had no other choice but to pay for the same ground over snd over for 30 years (plaque attack). Again, there is now a new sheriff in town. Cool. We now move to new ground / at long last/ pay once…Higher ground.
We got this.
My views respectfully submitted,
Bio
SAS after hours PR?
One step closer to check mate…
Thanks for the generous invitation, kevli - it’s not complicated but I will compose a piece describing the situation as it stands and as I see it moving forward.
Will shoot that to you when completed.
GLTU
Bio
We have a milestone in our midst today:
Bob Dylan - 80 years old!!
Here’s a tribute to all of his contemporaries, with and without neurodegenerative diseases - this is for everybody!
We already know, as we finish each day, the times are a changin - so please keep the following in mind and heed it!
Enjoy! - and spin your fave Dylan cut today!!
Thanks for the link.
Here’s one affiliated with Dr Rudy Tanzi at Mass Gen Hospital.
“The higher prevalence of AD in females was largely assumed to be due to their longer life spans compared to men but recent studies are beginning to paint a more complex picture.”
https://www.nature.com/articles/s41598-018-25377-w
Guess these differences have yet to “fill the gap”?
Bio
“Not to mention Anavex only diluted 551,068 shares from 2/12/21 - 5/11/21”
Quote
Recall, Institutions bought roughly 2M shares during that same time period.
Whether they were managed funds or indexes...the significance is that, if Missling knew the indexes had to buy in at these prices, or, if he concluded that they chose to buy, the strategy tells him that either way...they are “in” at prices in the elevens to sixteens and he has institutional base at a higher floor when he needs to raise capital in future.
He DIDN’T dilute sooner than necessary. That’s a hat tip. He sees the board...
(Royal fork)
He also knows how we intend to play things. Example:
When asked on CC what he intends to do with the pediatric voucher - assuming it is achieved - he answered, “We haven’t thought about that yet.”
Hahahaha! That’s a perfectly elusive answer - He sure as Hell has thought about that! And not even a hint...
Silence is so accurate.
Thanks dholmes,
Bio
Their website (Annovis) is fairly comprehensive for a small company, agreed. Thanks to those who provided links.
Also, Dr Rudy Tanzi has posited a theory for the cause of Alzheimer’s Disease (his latest in a long line - but a very complex disease.)
Thanks for that post.
Additionally, Cassava is attempting to zero in on the cause and treatment of AD just as Anavex Life Sciences is.
Here’s what I believe is the unanswered high priced question:
Why are 2/3 sufferers of AD females?
Ok, neurotoxicity of the axonal transport should not affect females at twice the rate, nor has it been shown to. Missing piece, imo, and this should have consequences.
Dr Tanzi claims that sigma 1 receptor when antagonized stops Abeta build up.
But we have evidence that the S1r antagonist Haldol makes dementia patients worse - it worsens their dementia even inducing dementia when used for other purposes.
Cassava has not accounted for why their compound can address the insult to females which is occurring at twice the rate of males.
Anavex’s sigma 1 receptor agonist (not antagonist) has this going for it as regards the elusive piece female/male ratio (detectives and puzzle solvers make excellent scientists as they are not fully satisfied until all pieces fit together):
According to Dr Tangui Maurice, progesterone is the strongest inhibitor of the sigma 1 receptor. Females have greater progesterone acting to inhibit the S1r in their bodies for the majority of their lives.
If Dr Tanzi’s theory were correct, a greater number of females should be protected from developing Abeta plaque and Alzheimer’s Disease (shutting down the S1r endogenously much more than males). Does that not add up?
But, since this is NOT the case, and Anavex works in reverse, the case for Sigma 1 receptor being a factor in STOPPING or PROLONGING the onset of AD if working properly, is NOT a theory. It is the EVIDENCE which we must work backward from in order to “make every piece fit”. Women twice as much is not a theory. This is fact. Evidence. The clue, perhaps, to the whole problem?
As things appear now, until further notice, I stand by my very initial attempt to understand Who, What, Where, When, How...Why.
The story may not be over, but, for now, if an explanation is needed, that’s the most directly correlated scientifically documented one to fit.
Please submit a more convincing one as that would help solve this for a great many men and women.
Respectfully. Thanks for all the alternative contributions,
Bio
Agree - sticky the ENTIRE statement (not a subset)!
Speaks directly to the use of the terms “objectives” and “endpoints” as defined and used by the FDA and published and explained by that organization.
Here is the part which has been debated regarding PDD’s trials - and is missing from this excerpt but is found in the linked statement.
Ray, you, yourself, have stated that meeting objectives is not meeting endpoints and therefore PDD did not meet endpoints of PDD because Dr Missling used the term “met objectives”.
What’s this?
“First, we underscore the significance of a well-designed clinical trial when evaluating whether a medicine is safe and effective for a particular use. Well-designed trials have specific objectives, referred to as “endpoints”, “
- From the statement by FDA
OBJECTIVES, REFERRED TO AS ENDPOINTS. Direct quote from FDA
Debate appears to have swung in favor of these two being synonyms. Objectives = Endpoints
Ergo
Endpoints/ objectives of PDD met
Your move -
Biostockclub
Thanks, dholmes.
The credit goes to TTT for the post I saw earlier! He’s always on the leading edge of company info -
I just quoted the passage for my response.
No borrowed glory, here!
Thanks for the repost though for those who might have missed -
Shout out TTT - well done always!
Thanks dh,
Bio
Thank you.
Useful information for Anavex and in conjunction with prior privileged intel in an off-topic investment.
Muchas gracias!
Bio
Interesting comments, Boi, thank you.
Certainly food for thought. Short on time (the refrigerator repair guy is just finishing up here) and long on DD and posts - so, let me see what I can dig up to run through the thought processes to achieve maximum word count for a future post topic! Lol (groans heard all the way to the ‘Burgh!!!*)
Ok, looking forward to the long pricing strategy post now on my to do list:)
Folks - blame Boi!!! Hahaha!!!
All in jest - good to think about, thanks, Bud!
Bio
Thanks Doc.
I feel the $12,000-25,000 range is in line with a drug which performs modestly, but, if the recent statements made by Dr Missling that emphasize the halting and reversing ability more pan out, I think the price would be ranged up to get into the $30-40K area. We may differ a little, but I think that should be reasonable without excessive for a reversal or permanent halt.
Let me know what you think if that seems to mesh? We appear to be very close in the “moderate” performance designation.
Thanks much,
Bio