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Which happens randomly to be all associated with high blood plasma concentration?
Thank you for PM from you know who you are, which I don't have access to answer privately.
However, it is worthwhile to share the gist of it, as I read it, which was that Anavex is not the first or only company to take the Sigma-1 approach and therefore it is worth being cautious.
In one recent PR: “FUJIFILM Corporation (President: Kenji Sukeno) announced that the company's Alzheimer's Disease drug “T-817MA,” did not meet its primary study endpoints of cognition or global clinical function in its Phase II clinical trial conducted in the United States on patients with mild to moderate Alzheimer's Disease (AD). There were no significant differences in secondary outcomes. In exploratory analyses, change of the cerebrospinal fluid (CSF) biomarker phospho-tau (p-Tau) benefited from the higher dose treatment while hippocampal* volumes decreased less in the lower doses group with statistical significance. Post hoc analyses also suggested T-817MA treatment with shorter duration of illness and symptoms was associated with better cognitive outcomes with statistical significance”.
http://www.fujifilm.com/news/n170719.html
I seem to remember we have been here before perhaps even regarding FUJIFILM, that is; all Sigma-1 receptor compounds are not equal. This, among other properties, is borne out by the fact that A2-73 was granted a now expired patent as a novel Sigma-1 receptor agonist and now granted a patent in combination with Donepezil. In fact Anavex themselves have a portfolio of compounds with Sigma-1 receptor affinity, but with different chemical strutures e.g. A3-71 also with a granted patent.
The chemical structure of A2-73 looks like this:
https://pubchem.ncbi.nlm.nih.gov/compound/46932299#section=Top
whereas,
The structure of T-817MA is:
https://pubchem.ncbi.nlm.nih.gov/compound/11338749#section=Top
http://www.alzheimersanddementia.com/article/S1552-5260(15)02741-7/abstract#/article/S1552-5260(15)02741-7/abstract
"T-817MA showed the highest binding to s1 receptor among other central receptors. s1 receptor is reportedly involved in oxidative stress resistance and neuritogenesis, and therefore implicated in neurological and psychiatric disorders."
T-817MA is classified as a Neurotropin. I don't know much about chemistry and biology, but as I can understand it T-817MA is not the same class of compound as A2-73.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465887/
"T-817MA, a neuroprotective agent, prevents Aß-induced granule cell loss in the dentate gyrus of the hippocampus [149], and improves the motor and cognitive impairments owing to inhibiting neuronal degeneration in P301L tau transgenic mice [150]. The Phase II trial has been completed for its evaluations on safety and tolerability. Figure 10 & Table 6 list the main neurotrophins promoters."
The whole S1 affinity versus efficacy debate has already raged ad nauseam on the forum and not worth me going into.
Either way, your research on T-817MA shows that so far that compound was less useful than A2-73 still appears to be. One reason for that is that the not fully understood method of action of the two compounds is different.
Instead, in my simple view on the current situation the analysis boils down to:
1) Is Anavex at this point an investment opportunity with an attractive risk/rewards ratio based upon the science, data, financials, management and near term catalysts?
2) if your answer is no then don't invest or exit, but if yes then:
3) Await the next batch of trials and monitor how things evolve.
4) If/when the $AVXL share price climbs prior to trial readout, considered locking in some profit by selling a proportion of your position. The proportion depending on your circumstances and risk appetite combined with your assessment of changes in the risk/reward ratio along the way.
I am excited to follow what happens next in the Anavex story, the potential is there for a truly amazing breakthrough in the treatment of CNS diseases.
Inclusion/exclusion criteria based upon KEM analysis extended by DNA/RNA profiling along with gut biome data.
As a PR bonus following CTAD perhaps Part C longitudinal data and update on how the patients are doing now. As extra bonus more concrete information on trial start.
What have I missed or what else could it be?
The longer we wait the more correct you will be, until hopefully one day you will be proven wrong.
Actually they are selling to me
I can only suppose you mean this as some kind of joke.
If all what we know about A2-73 holds up in trials, it truly is amazingly good news!
Just out:
Press Release: Anavex Life Sciences Announces New Data Related to Multiple Sclerosis Presented at 7th ECTRIMS-ACTRIMS Meeting MSPARIS2017
Anavex Life Sciences Announces New Data Related to Multiple Sclerosis Presented at 7th ECTRIMS-ACTRIMS Meeting MSPARIS2017
ANAVEX(R) 2-73 Shown to Protect and Repair Myelin Forming Cells
NEW YORK, Oct. 27, 2017 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (Anavex or the Company) (Nasdaq:AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental diseases including Alzheimer's disease, other central nervous system (CNS) diseases, pain and various types of cancer, today announced additional data from a preclinical study of ANAVEX(R)2-73 related to multiple sclerosis. The data was presented in an oral presentation by lead investigator, Robert Lisak, MD, Professor of Neurology at Wayne State University School of Medicine, at the 7(th) Joint ECTRIMS-ACTRIMS Meeting MSPARIS2017.
Oral Presentation Details:
Session: Remyelination: from biology to clinical trials
Title: Sigma 1 receptor agonists as potential
protective and reparative therapy in multiple
sclerosis
Date: October 27, 2017
Time: 2:52 pm ECT
Location: Hall B, Le Palais des Congrès de Paris
2 Place de la Porte Maillot
75017 Paris, France
"A unique feature of ANAVEX2-73, compared to another sigma-1 receptor agonist we studied, is that ANAVEX2-73 accelerates the maturation of oligodendrocyte precursor cells (OPC) to oligodendrocytes (OL)," said Dr Robert P. Lisak. "This is an important feature since OPCs can replace lost OLs by maturing into new potential myelin-producing cells. In other words, ANAVEX2-73 might promote remyelination. Further data also demonstrates that ANAVEX2-73 provides protection for OL, OPCs, as well as central nervous system neurons in addition to helping repair by increasing OPC proliferation and maturation in tissue culture."
"These findings provide additional evidence for the neuroprotective and neurorestorative effects of ANAVEX2-73, as well as further validating the mechanism of our target," said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex.
All good, but with this:
Guess what else that describes perfectly? A company raising capital via an ELOC agreement!
Perfect thank you!
Ok thanks. A cautious guess might be that we will see an increase in short interest...
Despite hopes that short interest would be easing based on the catalyst PRs that should see an increase in share price.
So because shares yet to settle could be a relatively large proportion of the data it can be misleading in terms of understanding short sale volume.
But 2 days hence shares are settled leaving a clean short sale volume figure. Do we assume that the chart is not continuously updated 2 business days back to truly show short volume?
I really just want to know if short selling is accelerating or if we are instead in a cover short interest phase.
Do we conclude that we must await the next twice monthly nasdaq short interest update to know for sure?
I am still at a loss to understand. If it doesn't represent shares sold short, then what does it represent and thus why is it useless?
I am looking to understand what data drives the chart and it's source.
Could you explain what Short Volume from that site is, rather than what it is not?
The short volume has been climbing over the last 10 days, but comparatively a declining proportion of overall volume.
https://fintel.io/ss/us/avxl
So, if I read the chart correctly, accumulation seems to be going on. If we do get major news over the coming days, covering increasing short interest could become expensive.
Shame that short interest data is lacking two weeks behind.
True, it is probably about 16 years ago I worked on projects for HypoVereinsbank in Munich and those guys scrutinise everything you say and wants every detail documented. That is a big reason I am confident in our Bavarian Chief.
Yeah and guess who paid for it!
Had to steel that one before somebody else.
When I look across biotech stocks today they mostly behaved very similar AVXL.
The science and near term catalysts haven’t changed and we have a picture today of a confident looking Bavarian chief.
Indeed biotech has headed broadly downwards the last few days with the rest of the equity market wobbly too.
Meanwhile Anavex science and near term catalysts remains unchanged.
I am holding and expect in due course the lows will be forgotten and meaningless, but admittedly at present I do feel royally screwed - not that I have any reference experience to draw on.
And all done by algorithms?
Cannot be excluded, but I sincerely hope not
I'm looking at the filings list that appear when viewing posts, where the latest purchase is 10/19. Perhaps it is elsewhere on the site?
Yes, but you are missing the point about large orders and minimising price impact using high speed computers and low latency connections to markets.
IMHO, $AVXL is not a stock that fits algo trading. If you have invested in the quants, programmers, computing power and low latency connections, you would not spend it on a stock like $AVXL.
We agree that there appears to be orders, buying and selling that looks like 'manipulation'.
But, as for the algo stuff let's leave it there and agree to disagree.
Good old Wikipedia https://en.wikipedia.org/wiki/Algorithmic_trading
There are no consistent large orders volume in $AVXL (yet) to chop into bits by algos in order to minimise price impact of execution.
A stock like $AVXL, in my view and understanding, is simply too volatile and erratic and on low volumes to represent valid learning material for an algorithm to be worthwhile. There are much better stocks to spend the compute time on.
But what do I know, I've only spent some 30 years of my life on financial systems.
A lot of folks here talk about Algorithmic and High Frequency Trading, but I suspect without really appreciating what it means and how it is applied.
Here is quick overview https://c.mql5.com/forextsd/forum/168/high-frequency_trading_-_better_than_its_reputation.pdf
I doubt that many super computer time cycles are expended on a stock like $AVXL.
No need for Algorithmic and certainly not High Frequency Trading here, which are both geared towards high volumes while avoiding much impact on price. It is an arbitrage of small trades at high speeds extracting small gains just a little bit higher than the cost of execution, but with a statically acceptable certainty.
If there is 'manipulation', which is more than likely, then it is just a couple of dudes or dudesses playing at low volumes to snatch and accumulate either for themselves or clients. And why, of course because they too understand and expect, based on the science fundamentals, that Anavex is an investment that has potential to rocket on upcoming catalysts.
I make it that about 65% of the outstanding AVXL shares are on retail hands, or least not institutions and insiders.
I doubt the proposal that the vast majority of those 65% Anavex investors have no clue about the science, but instead just randomly and blindfolded put some money towards a stock like Anavex.
Think about it, overall for a long time much written about Anavex on retail hangouts has had a negative sentiment based on anything but the science, with just a few science minded writers digging deeper and explaining why A2-73 might work and is different from the 99.8% attempts at Alzheimer's that so far failed. Anavex is not a cult stock like $AAPL that everybody invest in, some just because everybody else does.
Judging by the posts here and some other of the more civilised message board hangouts, I get the sense that AVXL retail investors are savvy by experience, curiosity and education or combination thereof. It doesn't require a background in a relevant science to be an investor, you just need to not be a fool and be curious, interested in researching and learning and of course to be careful.
GLTA
Re. short positions days to cover.
http://www.nasdaq.com/symbol/avxl/short-interest
The table is up to date as of 13th October and since then the average daily volume has been 375,845 shares. At this volume it will still take a couple of weeks to cover the about 4M shares shorted!
Unless most of us are delusional about the next couple of weeks, Anavex will most likely issue several price moving PR's. We must assume Shorts, as much as they might not like it, are aware that it is time to cover.
Watching Level 2 yesterday, there was a significant gap between trading and the next levels down on the bid/ask. Trading was some 20 cents below the next bid/offer levels. In other words just a few parties playing ping pong on very little 'artificial' volume to drive down the price, while desperately snatching up any small bit of real volume dripping down from stop losses, day trading and perhaps a few chicken investors.
So again, unless Missling has himself, the SAB, insiders and about 65% retail ownership deluded about the data, trials starting and funding for them, then there is a 4M shares short squeeze on the horizon!
Now just close your eyes, stay long and look back at this post in a month - will it be heads or tails?
All of course just IMHO and not investment advice! For that I would listen to the kind protectors of unsophisticated investors.
How come iHUB is still not showing Missling's latest $375 purchase?
$375 is a popular amount.
I believe the thanks should really be directed to Einstein.
Predictions are difficult, especially about the future.
Somehow I don't think the shorts will make it home and dry before more great PR sweeps them off the ground to dizzying heights. The action today indicates to me that they know it.
Btw. tomorrow is Thursday, Missling's favourite PR day.
L2 has big price gap between the top and next bid and ask in the stack. Someone is clearly playing with themselves.
Is there a sarcasm flag I can use as appropriate with some of my posts?
Just in cases where it isn’t clear to all.
Yes by now Missling has probably realised that he shouldn't have held a special conference call about the PK/PD and Ariana findings. After all the old Corp. presentation he is used to giving in his sleep, whereas the other new science stuff would just bore folks to death.
The market overall down today with NBI down 1.51% and IBB 1.56%. When that happens small and assumed more risky Biotechs are hit hard. No doubt further exploited by those with an interest in lower prices.
In fact it looks to me like overall the markets could be about to turn south after a very long and strong upturn.
Can great AVXL news soon muscle through a downturn?
Thanks. Either way it is a mute suggestion, unless Missling is repeatedly lying.
Yes I forgot that and F1ash promptly posted the terms.