I suspect that's right.

I think holding Anavex to the politicking standards of Biogen and Lilly is a bit unrealistic. Anavex will ultimately let the regulatory decisions speak for themselves.

What conspiracy theories are you referring to?

Given your description of blarcamesine's merits, the advancing regulatory process in Europe, and Anavex's strategically strong cash position (~ 4 years of runway against a year or two of waiting on regulators), why are shorts significantly increasing their already heavy position in the stock? And why are they -- so far -- getting away with driving down the stock price to this rock bottom level?

In a rational market uncorrupted by gamesmanship, we shouldn't be seeing this combination of circumstances. What is the shorts' exit strategy? Do they simply refuse to believe that a small biotech with a unique drug platform can have any chance of a regulatory approval -- or are they trying to force a lowball buyout?

To the extent that Missling has from the start, and unconventionally, built up Anavex's finances and low share count without resorting to help from an investment house or a partner, he has placed the company alone in the marketplace without a strong institutional defender against organized shorts. Of course, choosing the conventional route would have come at a high price to retail stockholders like us -- much greater dilution and a loss of control against a buyout.

Either of Missling's early financing choices came with a price. Unusually, he seems to have picked what turns out to be the high risk/high reward choice. It bespeaks Missling's firm belief in the science and in his ultimate ability to deliver drug approvals. (I don't think many CEOs could even have carried this option this far without having had to resort to much greater dilution.)

So Missling is partly responsible for setting the preliminary conditions that allowed this game of chicken to develop, and the hedge funds attacking the share price today are also clearly responsible. What is missing is a belief by the general market -- conditioned to failed AD drugs -- that an unknown drug by an unknown pre revenue biotech has any chance of success. It would be too good to be true.

No, that isn't a material event. Just answering.

Anavex used the preclinical reference because they did not want to explicitly claim that the 2b/3 showed "a potential to halt and/or reverse the course of Alzheimer's disease." That would be an overstatement that could get them in trouble. Of course, the drug doesn't need to have done that well in order to get regulatory approvals.

You aren't familiar with the retail base. And an offer like that to the BOD wouldn't even get to the shareholders. If this is your premise for being in the stock, you should move on.

The company is not buyable for such a low price. Missling and other BOD members will reject that, as will a very dedicated, rather large retail base. The company has legal anti takeover defenses in place and plenty of cash to keep operating.

The company is not yet at a stage where they need marketing staff. Missling is careful with money, and he won't waste it on paying staff he presently doesn't need.

Missling seems to have built a diverse workforce, which is a better strategy than limiting the talent pool to just white guys.

Why do you think Anavex is being blinded from its unblinded AD OLE?

All the SAVA claims presently rest on unblinded data.

Anavex is in the pre-application process for an MAA.

If the FDA were to involve itself in ending trials for efficacy, as you suggest, it would requires orders of magnitude of greater resources. This is not going to happen.

He also posits that the benefits of Simulfilam evaporate after 18 months, so don't get carried away.

I am really getting tired of your bad faith arguments, especially considering you just claimed to have bought more AVXL.

A new statistical analysis by Anavex of the same underlying data does not represent cherry picking the data. And its dosed arm of 338 is significantly greater than a post hoc subset of 90.

Furthermore, in light of the emerging FDA approach to early AD trials, Anavex is simply using the ADAS-Cog endpoint as its sole basis for seeking FDA approval. This puts the company in an excellent position to file an NDA to go along with its regulatory progress with the EU, since the gatekeeping p value reverts to .05, which has been easily met by the 2b/3 AD cognitive p value of .0226.

And the reason I accuse you of bad faith is I know you understand all this, yet continue to post your BS.

ANVS reported on a subset n of 90 using criteria that had not been pre-specified. So no, not pivotal, and not analogous to our 2b/3, either.

I just watched the presentation last night, and was struck by a couple of asides.

First -- and this shouldn't have been surprising -- Missling has abandoned the combined .025 standard for both ADAS-Cog and CDR-SB that Kun Jin adopted in favor of a straightforward .05 p value standard for ADAS-Cog alone. With the FDA draft guidance abandoning the ADL co-primary endpoint, the multiplicity issue has disappeared. So, going forward, we see that the small, 508 n Anavex AD 2b/3 is not squeaking by on p values; instead, it's a convincing win with a cognition p value of .0226 blowing past the .05 gatekeeping figure. (Not to mention the biomarker support.) In other words, if you have the goods, you no longer have to have designed an 18 month AD trial, let alone a trial with an n that's triple the size. Keep that approach for the weak and relatively dangerous mab drugs, though. Those trials need the extra power to show results.

Second, Missling made almost a throwaway remark that some patients had their brain volume loss "reversed." It's hard to imagine he meant they gained brain volume, so I will assume these patients had pathological brain volume loss stopped. In either case, I have cause to doubt my earlier calculations of an average ~20 percent reduction in volume loss as being too low.

Finally, Missling made reference to upcoming updates. Here's one I am watching for: We are coming up on the time in the EMA pre submission process (perhaps as soon as a month away) when Anavex might announce its intent to seek a request for an accelerated review. If we don't see this, no big deal. But if we do, take that as a sign of strength and a sign that it's likely to happen.

Frrol has long displayed reading difficulties with material he doesn't like.

Draft guidances can be informally governing, so long as they fall within the range of an Agency's discretion and there are no outstanding rules to the contrary. I have written a draft guidance that was applied in this circumstance, as well as a proposed regulation. Both were procedural.

Conspiracies? Underpowered?

You have a reading problem.

The question of a filed MAA and an approved application are distinct, and are separated by about 15 percent.

I still haven't seen a reasoned post explaining why Anavex will not file an MAA.

I guess you are one of those people who believe in a fully rational market for all stocks at all times. I think that belief is ridiculous.

I don't know how you come to your conclusions about the Anavex trials.

1. The AD trial prospects are looking better than ever, given (1) the CHMP go ahead for filing an MAA; and, (2) the draft FDA guidance pretty much obviating the need for an ADL endpoint win, validating Kun Jin's .025 ADAS-Cog/CDR-SB choice.

2. The Rett trial was not a drug fail; it was a trial design fail. Not good, of course, but not at all a repudiation of 2-73's efficacy in this indication.

3. As for schizo, we are dealing with a 3-71 trial.

Whatever your perception of other people's perception, the Anavex clinical program is very much alive, with a solid cash position for the upcoming AD regulatory season.

Missling has indicated it has been accepted, but of course the time line isn't working.

I would consider this a more critical matter if CHMP hadn't already cleared an MAA.

See next message.

If they are legally incompetent then a guardian will make the decision.

I have yet to see a reasoned post explaining why Anavex will not be submitting an MAA -- just the usual disgruntled mutterings about Missling.

The study is inpatient at a facility in New Jersey.

I think I have seen somewhere that a proposed drug's European trade name is disclosed in its MAA.

It means the summer of 2024.

I guess they've fixed the Three Gorges Dam. Or maybe the media you watch has stopped talking about. Good news for Anavex!

I'd worry more about Miami slipping away than NYC.

I'm not quite sure what you are asking, but on my computer you can see poster names when you hover the cursor over the icons. I don't know how to work this on a phone, which doesn't use a cursor.

I have to admit the discussion of the peer review has been confusing. While the entire process can take quite some time, as you have noted, the great majority of that time is spent in the journal's peer review evaluation process, i.e., whether to publish the submittal. Once it has survived peer review, the remaining process should be brief.

We were told in the last few months of 2023 that Anavex would provide the full data for the AD 2b/3 trial before 2024. Then, however, that deadline was lifted when Missling said that the timing was out of his hands because the data was going to be published in a journal. So that's all good.

The problem is, we are still waiting well beyond the normal time for publication after a proposed article would have passed peer review and the minor editing/formatting that follows.

I can only imagine a couple of possibilities: First, that the authors and the journal are still discussing the scope of what will be published (perhaps because of late breaking additional data), or because the journal has on its own some unusual internal delays. Someone with experience in this process will have greater insight. But I believe, based on what we've been told, that we are past the normal, lengthy peer review time frame -- but quite where we are is a bit of a mystery.

I think it's the overtime.

No.

I don't know what your definition of "we got this" is, but it doesn't match mine. I have never said "we got this."

As for "statistical finessing," I am old enough to remember Doc himself conceding that the Kun Jin .025 test was legit support for the claim that the 2b/3 AD trial succeeded, although saying it required further validation for purposes of regulatory approval. Since then, and without further information, he has managed to convince himself even the .025 test here can't be true. Confirmation bias, I guess.

As I and others have explained to you, you have nothing more than your opinion to challenge the fact of the 85% EMA stat and, frankly, your bias is on display with every post. You have even reached the point of persuading yourself of a significant CHMP "validation" hurdle upon filing an MAA, for which there is no evidence whatsoever, while ignoring that Anavex has already received CHMP validation through its green lighting of an MAA several months ago. CHMP didn't do this without first seeing all the relevant trial data. Do you think they didn't read the critical few pages of the SAP for context?

With the exception of his earlier misstep regarding conceding the validity of the .025 test, Doc has missed no opportunity to take every adverse inference he can find. Even today's questioning of the brain volume data, for example, which is really a stretch, given the reliability of MRIs and the clear import of retaining brain volume in AD. (If I recall correctly, the weakest Anavex p value stat there related to the parietal lobe which, as it turns out, is less affected than other brain regions during early stage AD. A weaker -- but still stat sig -- p value for that lobe is therefore consistent with an inference of blarcamesine's clinical effect on the course of AD.)

In older posts, Doc has noted (1) his expertise in MS (a Biogen speciality), as well as clinical trials; (2) his personal acquaintance with the former Biogen CSO (before he was fired for his role in the Aduhelm scandal); (3) his willingness to use Aduhelm in his clinic (before Biogen withdrew the drug); and, (4) the opinions of his peers on the specific length and n of a recommended second 2-73 AD trial (certainly not a Facebook group, my inference being that they are a competitor's expert group). The Biogen connection seems apparent.

I think Doc believes what he says, but I also think he is professionally anchored as an Anavex opponent; I don't believe he will ever change his opinion of Anavex's research and trials. And this is a familiar phenomenon: As Max Planck famously said, science advances one funeral at a time. (I expect in this instance we won't have to wait quite that long.)

A great deal of the arguments against the legitimacy of the Anavex claims involve the extended time lines we are experiencing. The unstated premise is there is only one possible schedule in which every CEO can proceed in drug development, and a failure to conform to that schedule demonstrates a drug has failed.

This is a behavioral analysis, and perhaps an historical analysis, but it is not a form of scientific proof. Missling clearly does not fit the mold in his communications; he really says very little compared to other CEOs. This could be from personal preference, his history with shorts in 2015, his choice of advisors, or his perceived need for initial concealment when challenging scientific orthodoxy.

On the other hand, if Missling were conducting a fraud he would not invest in and be able to produce supporting research, attract legitimate scientific talent such as Sabbagh and Jin, or maintain good financials. He would not have been able to get any form of CHMP approval. He would do much more in the short term to pump up the share price (which has been conspicuously lacking).

My conclusion is that the company understands what it is up against, both in the challenge of demonstrating fundamentally new science and overcoming entrenched old guard opposition. It therefore must take the time to marshall all its evidence -- certainly, including the almost completed AD OLE.

The curtain is about to be pulled back on the data, and much of this scientific controversy will be resolved. In the relatively near term, we will get answers from regulators and we will know the fate of the company. Meanwhile, as Steady likes to say, the rest is entertainment.

As investors, we need to weigh Kun Jin's judgment against Doc's. We also know Kun Jin has seen everything.

Remotely possible. Let's say, perhaps, 15 percent.