Powerwalker:

Whether or not the YE is September or December is irrelevant to the fact that the calendar YE is fast approaching, and we have yet to announce 1 fully enrolled trial. Any way you look at that, it is not a good view.

Anyway, I pasted in this article below that I read before about a company (ProMIS) that seems to be scientifically approaching CNS in a similar manner to Anavex. The article mentions the potential for partnering with several large biotech companies in the future. I highlighted that statement in particular in bold type.

So, while we await news from Dr. Missling, it appears the rest of the science community is not sitting idle in its approach to targeting and treating CNS. Thus, the reason why it is imperative to get these trials fully enrolled ASAP.

Business
ProMIS Neurosciences issues Chairman's update memorandum and white paper on Alzheimer's disease
CNW Group CNW Group Thu, Oct 24 3:00 AM EDT
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New resources detail positive impact of aducanumab pivotal trial results and recent progress of ProMIS pipeline programs

TORONTO and CAMBRIDGE, MA , Oct. 24, 2019 /CNW/ - ProMIS Neurosciences, Inc. (PMN.TO) (ARFXF), a biotechnology company focused on the discovery and development of antibody therapeutics targeting toxic oligomers implicated in the development of neurodegenerative diseases, has issued a memorandum, compiled by its Executive Chairman of the Board, that provides context for the company's recent program progress as well as a white paper analysis of Biogen's October 22, 2019 decision to submit its amyloid-beta (Aß)-targeting drug candidate, aducanumab for Alzheimer's disease (AD) to the U.S. Food and Drug administration (FDA) in early 2020. The new resources detail how each development demonstrates strong momentum across the company's preclinical programs.

ProMIS Neurosciences Inc. (CNW Group/ProMIS Neurosciences Inc.)

On October 22, 2019 , Biogen announced that the conclusions from aducanumab's interim analysis for futility, disclosed on March 21, 2019 , were incorrect. Biogen also announced that analysis of additional trial data now indicates that aducanumab is effective in patients with longer term, high-dose exposure, and that they plan to file a marketing application with FDA early next year.

"We believe that over the coming months there will be a greater recognition of the likelihood that Biogen's aducanumab will be the first ever approved disease modifying therapy in Alzheimer's, although with a modest clinical benefit," said Eugene Williams , Executive Chairman, ProMIS Neurosciences . "It will change the thinking about amyloid generally, and more people will understand the growing body of scientific literature showing that the toxic oligomer of amyloid is the critical target. Selectivity for the toxic oligomer, as demonstrated preclinically with ProMIS' candidate antibody therapeutic PMN310, will increasingly be recognized as a critical differentiator, the basis of 'best in class'. Those expectations could be very positive for ProMIS."

In October 2019 , the company announced significant progress on several of its antibody programs demonstrating the unique ability of its drug discovery and development platform to rapidly and cost-effectively discover, predict and validate antibody candidates that are highly selective for neurotoxic misfolded proteins. Each of these programs, briefly updated below, is the object of ongoing partnering discussions with several large pharmaceutical companies.[color=red][/color]

Parkinson's disease (PD) and Multiple System Atrophy (MSA)—preclinical in vitro studies, announced October 8 , indicate that antibody candidates targeting toxic forms of alpha-synuclein, a root cause of PD and MSA, bind strongly to toxic alpha-synuclein aggregates derived from MSA-affected brain. The antibodies also protect cultured neurons from alpha-synuclein toxicity and spreading (propagation).
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)—new data, announced October 22 , show several antibody candidates demonstrate selectivity for toxic, misfolded intracellular aggregates of TDP-43, a root cause of ALS and FTD, with no binding to normal TDP-43 located in the cell nucleus.
Alzheimer's disease—new data, announced October 17 , show several antibody candidates bind toxic forms of tau, a protein that can misfold and play a major role in disease progression. The antibodies also inhibit propagation of neurotoxic tau in a cellular model.

For access to the Chairman's Update please click on: http://bit.ly/ProMIS102319
The white paper is available by clicking on: http://bit.ly/ProMISWP102319

To learn more about the role of amyloid beta in Alzheimer's disease including evidence implicating the toxic oligomer, tune into Saving Minds, at iTunes or Spotify.

About ProMIS Neurosciences
ProMIS Neurosciences, Inc. is a development stage biotechnology company focused on discovering and developing antibody therapeutics selectively targeting toxic oligomers implicated in the development and progression of neurodegenerative diseases, in particular Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). The Company's proprietary target discovery platform is based on the use of two complementary thermodynamic, computational discovery engines – ProMIS and Collective Coordinates – to predict novel targets known as Disease Specific Epitopes on the molecular surface of misfolded proteins. Using this unique precision approach, the Company is developing novel antibody therapeutics for AD, ALS and PD. ProMIS is headquartered in Toronto, Ontario , with offices in Cambridge, Massachusetts . ProMIS is listed on the Toronto Stock Exchange under the symbol PMN, and on the OTCQB Venture Market under the symbol ARFXF.

Visit us at www.promisneurosciences.com, follow us on Twitter and LinkedIn.

The TSX has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. This information release contains certain forward-looking information. Such information involves known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from those implied by statements herein, and therefore these statements should not be read as guarantees of future performance or results. All forward-looking statements are based on the Company's current beliefs as well as assumptions made by and information currently available to it as well as other factors. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Due to risks and uncertainties, including the risks and uncertainties identified by the Company in its public securities filings, actual events may differ materially from current expectations. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

They haven’t announced full enrollment in any of the 3 trials (Rett, PDD, ALZ), which I believe is a significant headwind to any significant SP appreciation. I can understand why ALZ may not be fully enrolled yet, but Rett & PDD should be fully enrolled by now. We're a few weeks away from another quarterly report, and only 9 weeks away from Year End.

What is taking so long?

Canton s/b Cantor

I just finished listening to the Canton Presentation, and also agree with many on this board that it was, BY FAR, the best presentation that DM has EVER given about the overall company.

He made a compelling case for why the investment community should at least put us on a "watch list" of CNS stocks to own in a portfolio. For the first time in a long time, I feel very confident in our company's future prospects.

Well done, DM. I am hoping that between now and December 31st, we get all 3 trials fully enrolled (execution) so that 2020 can be a year of results.

If Missling has an Achilles Heel, it is in accurately projecting the timing of trials.

I agree with you that since we are not yet fully enrolled in PDD, there ism’t enough time left in 2019 to get any data readouts.

the Parkinson’s and Alzheimer’s trials are not yet finished.

Isn't it hard to finish these trials when they haven't been fully enrolled yet?

It would sure be nice to get a PR come Monday stating that PD has been fully enrolled.

I'm thinking this is what may also be holding back more SP appreciation.

I’m pretty much tapped out at 20K shares, so perhaps someone else has the “ dry powder” to enact your plan.

At this point, I’ve got more skin in the game than I am comfortable with given the lack of trial enrollment news. Oh well, hindsight is always 20//20.

Do you think by the time he makes this presentation in December we'll have a trial fully enrolled in any CNS indication?

It's wonderful news that we are starting yet another trial, but I think the market is dismissing this news because we have yet to fully enroll trials that have been started over a year ago.

Just an observation, but based upon the anemic SP appreciation of 3 cents on this news, it seems to be an accurate one.

The only condition A2-73 is not effective in treating is an ineffective CEO.

Is Dr. Missling's "speed dial" broken? Why have we yet to announce ONE fully enrolled trial? It's almost September.

Great job, Doc.

Your concerns haunt me as well. It would be more practical and prudent to stay focused, rather than keep adding on more indications when we have yet to prove any efficacy in human trials.

Get the trials fully enrolled, Doc! You should make this priority #1. You should not be allowed to attend any more conferences with free donuts and coffee until you achieve 100% enrollment.

I left one out from the CC. When the question was asked about why expenses increased, DM gave an answer about "an accounts payable accrual", without explaining what the payable was for.

Who gets away with these vague answers on a CC? Why, DM does.

This is sloppy, folks.

This is what happens when your CEO takes longer than anticipated to fully enroll trials.

I'm surprised this didn't happen on Wednesday and Thursday. I guess logic finally caught up to the share price.

Other than the H.C. Wainright analyst, the other 2 analysts on that CC were "in the tank" for Misssling.

"Oh, Chris, thanks for taking my question"

Give me a break!! How about a tough question--for once. Why the shelf? Why is enrollment taking so long? How much DOES it cost for a Rett trial patient in the US versus Australia? DM gave a BS answer that Australia reimburses 40 % of the costs, without giving the actual cost per patient.

This is sloppy, folks.

Do you find it convenient there is no mention of the Shelf?

DM had an opportunity today to really knock it out with news of fully enrolled trials, but once again stubbed his toe.

You’d think by now I’d be used to this, but on behalf of the shareholders and patients it is a kick in the gut.

In the 4+ years that I’ve been following the company, the answer is no.

What a disappointment. Despite this, I’m sure they’ll all get their performance bonuses. What a joke. Where are the company’s priorities? Going to conferences and touting their PM and showing 5 year old data? Maybe they should have put more focus and energy into getting trials enrolled.

“Advancing nicely” and “as scheduled” are euphemisms for the fact that the company has yet to fully enroll ONE trial.

This, and no mention of the shelf, explains why we are at $2.37 a share.

So much for “connecting the dots.” Unbelievable—what is taking so long?!!

When DM announced the shelf on July 3, the SP was $3.90. Today’s. close of $2.22 represents s $1.68, or 42% decline in 1 month.

Talk about shooting yourself in the foot. Ouch!

Hmmm....aren't we trying to help those who suffer from AZ? Yes

Hasn't our esteemed CEO said that "early detection" is critical? Yes

That is how it relates to Anavex.

Does the article mention Anavex? No

Not every article that is posted here has to specifically mention Anavex in order to educate the masses.

I just read this article about how research scientists believe they have developed a AZ blood test that is 94 % accurate in diagnosing those with early brain changes that eventually lead to AZ.

Hopefully you'll be able to read the link that I have provided:

https://www.yahoo.com/news/alzheimers-blood-test-proved-94-200043240.html

“This has become one pig of a stock.”

Correction: It has been a pig of a stock for quite some time.

I don't concern myself with whatever games WS plays with the SP. We can only control what we can, and that is making sure we are executing the timeframes set forth in DM's plan.

What I am concerned about is whether our CEO is achieving milestones towards these trial enrollments. Seems to reason you cannot report top line data on a trial that is not 100 % enrolled.

Some have suggested that we'll get results of Rett & PDD before EOY 2019, which seems to only be possible if we get a fully enrolled trial.

Trial Enrollment Updates?

We’re a few days away from August, and still no confirmation that we have any trial 100 % enrolled.

Disappointing and unacceptable. Thus another reason why we’re stuck at $2.50.

Yes, I thought the word “rapidly” was an interesting choice for a word as well, given how long many of us have been waiting for some news.

How about letting us know about trial enrollment?

I agree that only results matter, but 100 % enrollment needs to be communicated to investors so that we know that things are progressing—albeit at a snail’s pace.

Management doesn’t seem concerned about SP at this time, so this PR news should be made public once this milestone has been achieved. I believe even DM informed an analyst on the most recent CC that this would be made public once achieved.

Waiting until results are available from these trials (PDD & Rett) would just create tremendous uncertainty & nefative speculation about the company’s inability to fully enroll a trial.

Having said that, nothing (and I mean NOTHING) this company does surprises me anymore. I feel like I’m on a sailboat without the rudder.

I was referring more to just knowing when the trials are 100% enrolled—we can’t even start the countdown to trial readouts until the trials are fully enrolled.

We have to walk before we can run. Right now we’re crawling.

No, it sure doesn't, Mike. Nor do we have a management team that seems interested in promoting the company to the public--you need an "Anavex Decoder Ring" in order to understand the subliminal messaging that our esteemed CEO apparently is sending out to us. This decoder ring will help you "connect the dots."

I'm really hoping that things change for the better--and soon. I'm tired of hearing about how great things are going to be 6 months, 1 year, or whatever time period out into the future.

After hearing this for 4 years, it rings hollow. As a long term investor (yes, the IRS considers stock ownership of over 1 year as a long term investor--so I'm this times 3!!), this stock has been a horrid investment. I'm glad that I never recommended this to any friend or family member, as I would have probably not have many of them speaking to me by now.

Have a wonderful weekend, everyone. Get out there and enjoy some fresh air and nature! Maybe DM will finally get his act together next week.

Or he can just string us along for another couple of weeks and release it as part of the Quarterly report.

My vote is for whatever takes longer, so it’ll probably be 2 more weeks.

What is your one sentence message to our beaten up retail shareholders?

I'd love to hear what his answer to this question would be, since the overall financial market continues to appreciate while we languish.

My own wish is that he would try to improve upon communicating and reaching milestones in a timely manner--way too much time transpires between meaningful communication from the leadership of this company. And we have become too accustomed to the many delays that have plagued this company--whether it be to design better trials or just not properly executing a business plan.

While it is admirable that some on this board try to "connect the dots", this really should not be necessary if we had more effective communication.

10 weeks should not regularly pass by without any kind of update (other than PRs about Preferred & Shelf registrations). It gives the appearance of a small biotech money grab. Considering all that "should" be going on with these trials, more timely communication is a must. If not for quarterly CCs, we might not hear even anything for much longer time periods.

This needs to change, and soon.

I am not as convinced of this as you are.

I have maintained that the cabal DOES NOT control when DM has achieved 100% trial enrollment. If/When we announce this news AND the SP goes nowhere, then perhaps I may start to see your point of view.

Until then, this SP malaise is as much, if not more on, DM than anyone or anything else.

The price declined nearly 75 cents AND volume increased within the past few weeks. It would stand to reason they were able to convince quite a few people to part with their shares.

Some quick math: SP declines 75 cents within 2 weeks, then “rallies” 20 cents. Folks, we’re still DOWN 55 cents. Lastly, can this EVER hold an early morning “rally?” It is almost a guarantee this will give back most of what it increases as the day goes on.

We need an open that is +$2 and climbs throughout the day—not slowly retrenches.

Very frustrating....where are the trial enrollment updates, Doc!?

Up 4 cents in pre-market!! Be still my beating heart!!

Word must be getting out about our firehouse & iceberg!!

Don’t forget about the icebergs!!

Can we hold off on all of this “Missling is a genius” banter until he actually does something that moves the needle beyond $4 a share.

Geez....

When you apply and get accepted for a credit card, does your personal wealth increase?

Same is true for a company using a shelf.

Agreed, DMs actions lately have all the hallmarks of a shady CEO using shady financing.

I wish I could ignore some of these tell tale signs. DMs behavior contradicts what he has said during CCs, about having enough money to run these 3 trials—then filing a 250M shelf registration on the eve of a holiday, more or less trying to sneak it through,

Enough of his BS—he needs to get these 3 CNS trials 100 % enrolled quickly. He seems too focused on printing free money with Preferred's & Shelf. I’m sure he is preparing an alternate plan if A2-73 fails, which is why he did the Shady Shelf. He’ll try to convince whoever is left if A2-73 fails that A3-71 is the golden ticket.

Hopefully I’m wrong....

I totally agree with your summary.

Based upon your analysis and the SP decline, I think the message is clear. DM needs to stop presenting inconclusive or “massaged”data readouts, stop asking for more money (Preferred's) on top of more money (Shelf), and instead FOCUS on achieving 100 % trial enrollment. If he is so “confident” about his iceberg, the rest of this is just a distraction.

Period.

OK, valid point about the length of this trial, but the number of patients in the trial is not a statistically meaningful amount for most statisticians to make any valid or meaningful conclusions.

Despite what DM says he needs to make statistically meaningful statements (I believe he said only 3 patients!!), I believe most mathematicians would refute his statement.

Most would want an N approaching 500 to 1K from a diverse pool of patients, so even the trials that we are (trying) to enroll now will be initially questioned for statistically meaningful results, given the smaller N in the trials--precision medicine or not.