Apologies if already posted.

Stunning proposal. Obvious cynical, unethical play by the amyloid lobby.

It would also multiply the Stage 1 Alzheimer’s market by tens (or hundreds) of millions overnight.

If only there were safe, preventive care.


https://news.yahoo.com/inside-plan-diagnose-alzheimers-people-110032560.html

Well… when even the shorts are saying that a buy-out will double the stock price… I guess that is a good day for my investment. Lol

Good luck to all

Cheers

Mycroft

Bwahahaha.

Thank you. I needed that ridiculous argument to give me a belly laugh.

Cheers

Mycroft.

That beats me...but i am close behind you with my initial purchase.

Best of luck to us all!

Cheers

Mycroft

Re: Doc Analysis

Umm.. huh?

By your own analysis:

and



So you give 1-2% chance that Anavex both 1) pre-specified a primary endpoint of 50mg vs placebo and that the 2) resulting benefit (which we don't have but know the overall mean is high) is sufficient for Accelerated Approval?

I do appreciate your analysis on this board, but I don't think I am being a Polly Anna when I say that this assessment seems unnecessarily pessimistic.

Cheers

Mycroft

Thank you for your analysis, I replicated your number for ADCS-ADL.

We also need to factor in the pre-specified Sigmar1 gene into the analysis. 20% of the population should be a lower responder than wildtype.

That means the numbers may be even better than they appear.

Cheers,

Mycroft

Absolutely. Otherwise there would be no value in showing a lower dose drug response curve.

But showing a drug response curve is the foundation of small trial precision medicine. The 30mg dose showing less response than 50mg proves Anavex understands their compound better, not worse.

Cheers

Mycroft

Re: SAP

I am having trouble following your argument.

You say:

But you also quote Missling saying:


It says prespecified. But you arguing that Anavex did NOT submit the SAP plan to the FDA in advance of the study and one would be "stupid" to think he did?

Please explain.

Cheers,

Mycroft

Yes, as I recall from the literature the ideal combination seemed to be as a helper to S1 as opposed to a lead or sole target.

Cheers

Mycroft

Funny, that was my first thought as well. The NPV of Rett should shift based upon this output.

Let us say that A-273 gets approved for Rett in July of 2023. How does that impact your analysis? Do you consider the possibility of off label use?

Cheers

Mycroft

Re: 12/5 call

Your analysis seems fair.

My Notes:

Positive:
-Great news that they plan to aggressively talk to regulators in multiple regions. This is the key thing we want to hear.

-I am very happy that they stand behind their original numbers, as expected.

-I was happy to have Perry on the call. His presence is more symbolic than anything else but it gives his imprimatur to the authenticity of the calculation methodology.

-Directly comparing aduhelm and lecanemab was a great idea and well done. It cuts through confusion for new investors by giving an apples to apples. This should put to rest some (but not all) of the methodology pearl clutching that has been going on.

-Interesting he also mentioned working with patient advocacy organizations. CEOs often avoid mentioning this until they are sure they have a strong hand of cards to avoid appearing to pressure regulators. Hints that they may have started to stir up grass roots support to help get this on the regulatory radar.

-the direct comparison of once a day oral therapy with no real side effects vs the IVs and MRI to check for brain swelling is a good point that should be made more often going forward. Biogen found out that approval of an expensive drug with harsh side effects and dubious benefit will be rejected by the market.

Less Positive
-Conference call quality was poor. I've spoken to many CEOs who are frustrated by this exact problem. I assume the barking dog came from one of the guests like Perry. lol

-It would have been nice if the presentation was more polished, some additional prep would have helped this.


Neutral
-I did not expect additional detail or the 30mg vs 50mg comparison. I did not expect them to change their data methodology for this call. I am yearning to dig into that data but I would rather they take more time with the data than put out rushed numbers.

-I had hoped for better questions from professional analysts. They were slightly better than neutral for me.


Side note for investors new to pre-revenue bio-techs: Stock price is indicative of how close revenue may be. If the Street thinks you are 6 months away from revenue they will find another place to put their capital for 4 months. That's why the stock dropped with the Rett news being moved to Q2.

But small investors like us don't have the luxury of being out of the stock and then jumping in right before revenue is confirmed.. at least, not if we want to maximize our returns. So let the funds work their strategy and you work yours.

Dollar cost average your buys over time, hold the stock, and if you wish, trade 10%-20% of your position on the swings. If you have a big enough position and don't like to trade, learn how to sell calls for a little side income.

Just my two cents. Best of luck to all.

Cheers,

Mycroft

Yes, Missling seems correct in the calculation of the numbers as stated. To subtract the group averages (as some were doing) is not compatible with how Anavex stated its results.

Also, one wonders if Ananvex had sat on this material information to do more data work if critics would applaud or pivot the complaints.

Cheers

Mycroft

RE: Missling is correct

Missling is correct here. For individual patient outcome (which is how they stated the improvement in their presentation) this is the proper way to compute these numbers.

It doesn't mean that either method is “wrong”. They’re just measuring different things.

LINK to full text

Cheers

Mycroft

Re: Upset

There is so no reason to get upset. Emotion clouds analysis.



Did the companies that fail use Precision Medicine and a 'fail early' strategy to safeguard against wasting investor dollars? Because as an investor I very much like the Anavex approach.



Can I ask how long you have followed this company?

I have followed Missling for many years now. I must say that, if anything, he has been too understated in comparison to other non-revenue bio-tech CEOs.

I respect and understand his anti-hype strategy but at times selling the vision becomes necessary and his tendency to under-sell is not my preference.

That is what made this presentation so startling, they finally just stated the results in clear terms. I respect that very much. I also respect them having a meeting on Monday to walk us through it.



That CEO has my respect but not my investment dollars for his science.

Thank you for your analysis of the slide numbers. I plan to dig deeper into them over the weekend. Best of luck in your investments.

Cheers

Mycroft

That seems a fair analysis.

M

It is easy to win every long shot horse, my friend. Just bet on every long shot horse in every race.

You won't be profitable... but you will win every long shot.

The art/science is eliminating enough of the losers so that the long shots are actually profitable when they hit.

Edit: I'd point out that there are several people on this board who are ALREADY 100x at least on part of their investments in Anavex. That is what finding gems in the Pink Sheets will do for you. I wasn't in at .22 like some here but I did pretty well.

Cheers

Mycroft

Re: Paradigm shifts

Your point is well taken.

But in the case of the amyloid hypothesis, the market at large still hasn't thrown in the towel. There needs to be a paradigm shift.

Ditto for precision medicine where even people on this board still clutch their pearls over trial size and duration.

On the other hand, I'd say the market already embraces the idea that upstream "preventive cell health" is a worthy goal.

That is how my usage of the term differs from your own

Cheers

Mycroft

Re: Returns

Several... but that is the wrong question. The real question is how many investments failed in order find the ones that succeeded.

At a 10-to-1 return and if I wager $1... I need to pick a winner every ten investments in order to break even (every nine investments to turn a profit).

This is what poker players call cash odds vs pot odds to ensure you have a positive expectation on your bet.

There are all kinds of ways to invest. My risk profile is to create a fund of high risk/return ventures where any single winner will pay for the losses on the rest.

I am invested much more heavily in Anavex than a typical risk play because there are multiple ways to win big... e.g. 1) amyloid is flawed, 2) precision medicine is groundbreaking, or 3) both are true.

Best of luck.

Cheers

Mycroft

RE: AD Trial Results

Fireman,

It is hard to imagine better news than what we received last night. I haven't seen anything from the naysayers that stopped me from adding substantially to my position today.

The results speak for themselves. But what is more important to me is the understanding of the Method of Action (MOA) behind the results.

Across the Anavex trials we have seen that (1) genetic profile and (2) dosing level are key predictors of success.

So my first reaction to last night's PR was... sounds great... but does it confirm our MOA story that proves we know how this compound actually behaves in the human body?

After all, this is not some Big Pharma, 5000 person trial where the goal is: "throw a drug against the wall and see who doesn't have too much brain swelling".

This is precision medicine. I underscore this fact because I don't think the market has fully digested the paradigm shift (and investment opportunity) that this represents.

Thus, the hidden gem for me in the PR was the line that confirmed (1) genetic profile:

We don't have the detail data yet but reading between the lines it looks like we also confirmed (2) dose response curve.

If the AVERAGE response of people on the drug is +4 points... ye gods, how many points did the high responders go up? 6 points? 8!?

If those high responders are predicted by dose and genetics (as they certainly seem to be) then that's the ball game.

The rest is just silly FDA bureaucracy and Big Pharma financial games.

My rule of thumb for biotech investing is that you can only get a 100x return from a major paradigm shift where you are right and the market is wrong.

In this case, there are TWO major paradigm shifts. First that the amyloid hypothesis is deeply flawed and second that precision medicine is far superior to the historical 5,000 person trials that seek to find a +.5% response.

Anavex continues to be the embodiment of both of those major paradigm shifts... and 100x * 100x is a very big potential return indeed.

So I continue to accumulate at these 'firesale' prices and watch the emerging data with great interest.

Stay Frosty My Friend.

Cheers,

Mycroft

Indeed. Your analysis is not unreasonable.

The trouble with analysis of this company is even using the most conservative parameters you quickly get to absolutely absurd projections.

Here’s to the absurdity of life.

Cheers

Mycroft

Thank you my friend, to trade pre-revenue bio-techs you DO need nerves of steel like a professional poker player… or a fireman!

Congrats and hope all is well.

Cheers

Mycroft.

An honest trader is hard to find.

I might have sold calls going into this as well if I had the free time, especially after the Rett moved back to Q2.

I usually hedge those bets with way out of the money calls to guard against the big move.

You’re Old Guard and glad you’re still here.

Cheers

Mycroft.

Anavex stock still listed as halted on nasdaqtrader.com with no resumption datetime set.


Cheers

Mycroft

Please God may you be right. Because I would really, really love to buy 15k more shares tomorrow pre-market.

Cheers to us both.

Mycroft.

McFarlane says Anavex received the locked data yesterday and he received the slides in the previous hour before the presentation. Lol.

Cheers

Mycroft

Congrats all. As promised, first round is on me at the board after-party.

Cheers

Mycroft.

A most excellent and cogent analysis. Well done!

Cheers

Mycroft.

The data was Sketchy with a capital “S”

I attended the conference where they tried to sell the idea of efficacy from their dubious data results. It went over like a lead balloon with about 1000 scientists in attendance.

Cheers,

Mycroft

“Maybe the poop analysis will bear fruit.”

Haha! Got me with that line. ??

Cheers

Mycroft

Thank you my friend.

Still long as can be and awaiting the data.

You have to love the quote from the article I posted:

“Forsayeth says the amyloid hypothesis became “the scientific equivalent of the Ptolemaic model of the Solar System”, in which the Sun and the planets rotate around the Earth”

That macro falsehood is what we have known all to well on this board for years.

The dam may finally be crumbling.

Making money is great. But there are very few joys as sweet as the Contrarian who is finally proven to be right.

Cheers

Mycroft.

Wow. Not sure if this has been posted yet but worth a read.

https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease


Cheers

Mycroft

He is indeed a well known short attack henchman. Look for accumulation and upward movement. It is the second movement in this piece.

Cheers

Mycroft

Exactly my initial assessment confirmed by the author. This is a buying opportunity created by market overreaction.

Cheers

Mycroft

News Out:


In addition, prespecified patients with WT SIGMAR1 in the clinical trial demonstrated a clinically meaningful and statistically significant 14.5-point (p = 0.009) improvement over placebo in the RSBQ total score, the trial’s key efficacy endpoint. This magnitude of the improvement with ANAVEX®2-73 compares favorably to published data currently in clinical development, which reported an average difference of 4.4 points in RSBQ total score versus placebo, despite an advantage of higher dose and lower age compared to ANAVEX®2-73-RS-001 trial.[3]

The RSBQ demonstrated balanced improvements across all the instrument’s subscales during the trial period of 7 weeks, including general mood, breathing, hand behavior, repetitive face movements, body rocking, night-time behavior, fear/anxiety, walking/standing.

The Anxiety, Depression, and Mood Scale (ADAMS), which is a measure of anxiety and mood symptoms in individuals with intellectual disability, [4] has been clinically validated for use in Rett syndrome [5] and in Fragile X syndrome, [6] demonstrated clinically meaningful and statistically significant 12.9-point (p = 0.005) improvement for ANAVEX®2-73 treated adult patients with Rett syndrome vs placebo in prespecified patients with WT SIGMAR1.
The ADAMS also demonstrated balanced improvements across all different subscales during the trial period of 7 weeks, including manic/hyperactive behavior, depressed mood, social avoidance, general anxiety, obsessive compulsive behavior.

“The biomarker-driven clinical evidence is very exciting and opens the possibility of successful treatment for both adults and children with Rett syndrome and early interventions for modifying the course of the disease,” commented Walter E. Kaufmann, MD, Principal Investigator and Chief Medical Officer of Anavex. “The outcome of this trial is very promising in terms of both safety and clinical improvement. Despite the challenges of the older age of the cohort (patients were on average 24 years of age) and the relatively low dose (5 mg daily), ANAVEX®2-73 demonstrated clinically meaningful improvements in outcome measures evaluating multiple impairments, which are supported by correlations with objective biomarkers.”

Glad you’re still here and a special toast or all of the fallen

Cheers

Mycroft.

Indeed. I made a bit of money trading BIIB this past week. Corruption at the FDA just seemed (sadly) too easy a bet to pass on.

But that doesn’t solve the AD problem and AVXL still has a critical piece of the puzzle.

I’m out of BIIB BTW and (after a long shower) feeling good and am still very long AVXL

Cheers

Mycroft

Best of luck.

I myself am seriously considering moving into the hedge fund space using blockchain & smart contracts to open that world to ‘smaller’ investors.

Perhaps a crypto/blockchain which allows one to easily buy into the SigmaR space which would include Anavex and other companies with the Sigma target.

It’s a world of opportunity

Cheers

Mycroft

I would advise hold but not if over-extended.

Hell hath no fury like a wife surprised by a margin call. Congrats!

Cheers

Mycroft

Remind me some time to tell you my idea of a ‘short squeeze’ blockchain investment fund based on smart contracts where everyone is locked in and everyone gets paid when a trigger is hit.

If Anavex got a large block of steady hands the short squeeze would be tremendous.

Cheers

Mycroft