CLEAR SUMMARY:

1. ADAS-Cog: Treatment difference of 1.85.
2. CDR-SB: Treatment difference of 0.42.
3. ADCS-ADL: Treatment different of 3.5

Is it as clear and indisputable as above?

Was it "manipulation" though? What exactly do you think it was all about?

IMO -- it was a "perfect storm" of buying frenzy. Nothing illegal/objectionable about it. Thus, I wouldn't consider it "criminal" or objectionable --- and similarly, for the crazy down days. Thats the point.

What is manipulation?

Was the spike to $30 a manipulation? Sure seems like it now. Stock has no business to be in $30s then. Were those buyers manipulators and criminals?

You guys find the sellers over the last 2-3 days as shorts or MM/manipulators. Would you think the same if the stock were to indeed crash to $5 this week? Wouldn’t these sellers be considered way smarter than us, then?

POINT: In the market, there are sellers and buyers. People who trade against you (Ie sell, if you are buying or holding) aren’t criminals or manipulators. In most cases, they are smarter than us — that’s why we aren’t billionaires yet.

Your job is to make money — in spite of all the “manipulators” in the market. I don’t believe in manipulations — even if they do truly exist. To me that’s just selling for their own purpose (which could be shaking the tree, eg).

Missling seems “happy” — that’s my fair assessment of his state of being.

Would “mixed” results make him happy? I seriously doubt it!! He has wanted this trial to be PIVOTAL.

I think “mixed” results in my eyes is failure.

Now if only one primary endpoint is met (but the other is not net) — then it’s a success …. Since it could form a basis of submission.

Very balanced article from Edmund I on seekingalpha.

Are we confident that the TLR are not leaked? (Ie, not known to any who has had any impact on the share price yet)

Looks like you weren't around for PDD release …

Do I attribute AVXL’s success (if any) to Missling? NO.

I do admire his perhaps sincerely, simplicity, and scientific expertise. But, yes, I am disgusted by his inability to communicate accurately — he should have hired someone an expert at such matters.

How silly. You want to wait for 12-18 months (time to get Rett approved with voucher) to file an NDA worth 10s of billions — so you can get a 3-month review advantage??!! That too when Rett AP proviso is not guaranteed??

No, no, Missling may be a great scientist, but he’s a terrible — most terrible — communicator (PR-releaser).

1. Do you remember the absolute drivel PDD-trial data release PR and call? Completely incomplete and confusing, at so many levels. Not to mention that he took 6 months (!) to release that!!!

2. Ditto for the Rhett syndrome trialS. Compare that to the competition’s PR. He never released the RSBQ data yet on Avatar (after making the switch to RSBQ-AUC). Just two numbers — Sumit Roy asked him multiple times!! It’s just TWO NUMBERS (baseline and post-treatment, RSBQs). Had he released — it would have quashed all the negativities associated with AVATAR. Missling just doesn’t get it (as if he’s a scientist who is completely dumb about WS-communications))

3. I can guarantee you he’s going to do the same on Thursday. Just dish out some INCOMPLETE and/or confusing results!! He doesn’t have the guts to be transparent (in failure).

As you can see — I’m very upset at him — for consistent multi-month delays and confusing/incomplete PRs on TLD/R. Terrible.

I hold a boatload of shares since 2015, have added recently too … it’s like a lottery ticket for me .. so I’m being patient.

How can you possibly distinguish between short sales and sales?

Fundamentally, they are the SAME — except that shorts need to be covered later.

Whats TGD? I feel silly asking -- but I give up! :)

Thanks for correcting me.

Perhaps. But, you should know -- that stock market is hardly a machine (much less, a calibrated machine) --- and it is known for overreaction. So, one can't judge how much of a drop a certain issue justifies. IMO -- Monday sell-off's reason related to a combination of things makes sense -- chief among them being the 3-month Rhett delay. Just my opinion/assessment/imagination. Who knows the reality! :)

Thats exactly I was thinking -- that a large fraction of big money is betting on AVXL (at this point) for its Rhett drug being commercialized soon. Any delay on that front is going to be have a big negative reaction. Perhaps, the sell-off was a combination of Rhett-1Q-delay, Biogen's death, AD-readout jitters-and-FUD.

That's my best guess.

I still am mystified why AVXL has delayed TLR till now .... this can only mean "mixed" results, in my disappointed imagination.

FDA (full) approves a drug only if there is “substantial evidence” for efficacy.

Now what is efficacy? Best definition is “clinically meaningful benefit”.

FDA has explicitly said that they don’t mind if the benefit is “small” (but clinically meaningful) — but the evidence for it still needs to be “substantial”.

Safety is not really a stringent requirement (but efficacy is) —- but the benefit/risk ratio (judgement call) needs to be favorable.

In our context of AVXL, the benefit needs to be statistically significant AND high enough (since it’s only a single trial). Else, forget about approval. Don’t expect “unmet need” to soften FDA’s stance — you have no idea how hardened FDA was wrt SRPT even though the Congress begged for it (but yes, eventually approved after a lot of in-fighting and resignations).

No, it is the law. Two trials, or one compelling trial. Listen to SRPT’s AdCom (FDA presentation) if still not convinced.

What I’m saying is that safety is insufficient for approval (FDA will never approve and let insurance companies and pts decide; NEVER).

The LAW requires TWO trials that show “substantial evidence” of efficacy, or one trial if the trial’s evidence is compelling.

Of course, a company can always submit — but generally don’t. FDA can also refuse to FILE an NDA if data is very premature.

Now — regarding SRPT. It wasn’t that FDA approved without efficacy. But what happened (in very short) is that Janet Woodcock used her intuition on amount of dystrophin expression required to “reasonably predict clinic benefit” and pushed for approval against most other FDA staff. The phrase under quotes “reasonably … “ is in the law, so some uncertainty or intuition was allowed PER LAW.

Nope, that’s not how FDA works. They need substantial evidence for efficacy.

I know SRPT saga extremely well.

Does anyone know is single example where the results were PR-ed after 4+ months?

Second Q: A single example where positive TLD/R of a PIVOTAL trial were first disclosed in a conference?!

Oops. CEO certainly knows this )that attendees will have the abstracts). Then, how can this strategy be a good/fair idea.

Haha. Do you know the law of the land?

Can shorts sue the longs for manipulation?

Since when does CTAD has the presentation? BTW, CTAD management is certainly disjoint of Wall Street, but also unlikely to leak to stock market players. It would also count as insider trading crime — which now is scary enough that no one sensible/rich will risk it!

Irrespective:
I also find it very unlikely that the results are stellar/success. If the endpoints were met, it would be hugely silly to wait for 2-3 months just to be able to present in a conference something that’s worth 10s of billions.

My summary of CC:

Most/only positive quote: “We think we are in good shape”

Negative quotes: “I think it really depends on the data” [difficult to use these words if you know the data is great]

Time will tell! I’m ignoring todays action (well, it hurts though).

Thanks. I had gone yo SA and checked Avxl “news” … hasn’t found it. But with your reply I went to “earnings” and found it. Thanks.

Possible to email me the transcript?
anshu248 is the id. Yahoo.

When does Chris say the below? I have listened to the CC a few times -- but can't find the below. Can you let me know the exact time in the CC?

====================
Chief Executive Christopher Missling is upbeat about the upcoming results. “….we just have powered the study according to our knowledge from previous clinical trials. So we think we are in good shape. I would recommend to wait for December 01,” he said during the earnings call.

“… we think we are in good shape…”. We will have to wait and see how if that turns out to be true.

There is no approval mechanism (other than AA) which is subject to an additional trial. AA is a very unique concept. It requires a surrogate/biological market or an intermediate end-point --- neither of which may be applicable to AVXL's drug.

Point: Either AVXL's ad drug would be approval or not. There is nothing like approval conditioned on an additional trial (except for AA, which is very likely not applicable here).

Why the 4-5 months delay in releasing TLR?

Other than CTAD, what could possibly be a reason to delay release of Alz trial results? AVXL did the same for PDD trial results -- and when they did release the results, they completely botched it (as they did with Rhett trial data)! As if they don't know how to PR results.

I'm sure some (including me) think that they are taking the time to do some data engineering/mining, when the primary/secondary have not been met fully. Who knows.

Can someone give me some good argument(s)? OTHER THAN CTAD (which itself as a reason doesn't make sense -- but I don't want to get into that argument yet).

Thanks! (I have a big position in AVXL since the early days .. 2015 I think .. waiting for a windfall one day ... ).