Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Perhaps. The potential will be much better reflected in the stock price — if CM is replaced.
Could FDA accept OR metrics as basis for approval (assuming that they were indeed pre-specified)?
I doubt it. Is there a precedence? I don’t know if any. If there is no precedence, what argument can FDA have against it (if let’s say # of improved patients is sufficiently high)?
One thing at a time, JKS. I am not at p-values yet.
1. Is it possible that OR outcomes was the intention all along, and they were specified as such in the SAP?
2. If yes, would FDA find these measures sufficient for approval?
Which part is impossible? That there is no SAP? There certainly is, as per CM in the CC.
Is it possible, that CM has been telling the full truth? Ie, the OR measures were truly the outcome measure intended all along (Ie in SAP, communicated to FDA, not necessarily approved).
I’d say it’s possible. And, if that’s the case — would FDA accept these for approval? I don’t have a strong argument against it.
One shouldn’t preclude the above possibility. There is no reason to believe it’s less likely than the currently prevailing presumption.
Every single PUBLIC company can be taken over.
So, a CEO should delay start of trials — so as to maximize the speculative impact on share price?! Wow.
Anshu i disagree with your valuation for buyout. There is no way if even 20 percent improve on drug that this will only be worth 2 billion.
Confirmatory trial HAS to be a well-controlled trial. OLE will never work for it.
You think the CEO does any better?
Appended to the post.
Every question must be answered, every data point a stunning masterpiece of clarity. No equivocating
No, I seriously doubt that CEO gets it.
TLR may be released — many times — but would it really clarify matters? Would it be presented like most credible companies do? Would it leave the market only all the more confused?
If the upcoming TLR really makes things crystal clear — whether good or bad — I’ll be stunned!! But, very happy.
Which side do you want to be?
Negatives:
1. CEO goofs up TLD releases, possibly, even twisting the truth, hiding key data points, changing endpoints. THREE times.
2. FDA may require P3 for AD.
Positives.
1. Just based on what is publicly known, the company can be bought out for $15-20, IMO.
2. Considering ADs drug failures to date, FDA may give AVXL a chance to file and review based on P2b/3 results. CDR-SB and Cog endpoints were certainly positively met. Upcoming data details may be positive. If FDA is open/sympathetic, AA can’t be ruled out.
3. Rett data’s positives are difficult to dispute (I also believe Avatar’s RSBQ-delra was very positive, even though CM didn’t disclose). So, post-excellence, approval should be on the cards.
I’m stuck on the long side; hoping for the positives, infuriated by negative #1.
I seriously doubt it!!
Yes, positives noted. But, have you completely missed the point of the negatives — which really need to be repeated over and over again (here, media, analysts, everywhere) until the thick-skinned CEO gets it!!
Yes, but for safety reasons the drug should have been used on sufficient many patients across trials. I don’t think that’s an issue for 2-73.
AD drugs typically use very large trials because they are expecting the difference in effect to be small — in which case you need a larger trial (to get low p value).
How is it that CM is the only one in the whole wide world who think’s differently? Listen to his reply to S Roy in the CC. Unbelievable—he thinks the whole world is a fool.
Why not short BIIB then?
Awesome update.
I hope CM gets it right this time!
Do you realize that showing mean-change if ADCS-ADL takes 5 mins, and this is something being pointed out by everyone relevant as conspicuously missing?
What do you assume the reason to be — except that CM is making a fool of everyone else (but actually himself).
BioChecker: I feel your energy is being uselessly wasted in your posts. I know you are frustrated and upset. I was too — but am better now. Do you think it would be more meaningful to instead do something about the frustration?
The only thing I can think of is to write a letter to the board. Do you think that’s a meaningful exercise? We could pool in together to write — but perhaps, we need numbers (number of people or total number/length-held of shares) to make impact?
Agree, high-level. However, you can’t deny that CEO’s job is also to communicate effectively with the investors — they are indirectly providing the funds to run the company.
A few weeks or 1-2 months of delay is not going to change anything .. neither would I consider it much if a miss.
Is there a material deadline that AVXL has missed significantly .. ie 3+ months .. for reasons internal? I can’t recall.
That WS/investors don’t believe his claims.
Sincere Q.
Is it really possible that the Board “gets it” and fires CM?
I really doubt it.
(1) CM’s -ve performance is only about communicating to WS, and not science or screw-ups with FDA (small delays are minor).
(2) Board has likely been fed CM’s reasoning — which is likely that if the data is bad, why reveal it and crash the stock … better to just hide it.
(3) Whoever got fired for similar reasons before.
BTW, to quote my favorite example, CG of SRPT was fired in 2014-2015 because of his not-so-polished/persuasive dealings/communications with FDA pre-approval (common perception, and my reading).
The WHOLE world is saying exactly the same thing (see below) — and CM still doesn’t get it. It really is a shame on his pedigree —U Munich and Kellogg. I’ll never look at Kellogg graduates the same way again.
https://www.fiercebiotech.com/special-reports/fierce-biotechs-rotten-tomatoes-2022
Ok. I feel confident that it’s very high (much higher than Acadia’) and in-line with the previous trail, and with low p value. But, yes, we won’t know.
CM answered the question about delta-RSBQ in conversation with Sumit Roy on that day. He estimated the delta RSBQ to be very high — based on other endpoints.
I really believe that delra-RSBQ was high enough in Avatar. That’s why I’m astounded as to why he didn’t release it.
CEO lying doesn’t mean the stock goes to zero. You think AAPL would go to cash value or so, if its CEO were to lie? You may just be finding excuses to justify your theories.
I only asked a Q. What possibility do you imagine? I NEVER claimed that he is lying — at most I have said he’s telling the half-truth or twisting or maybe lying (lying is very unlikely).
He will!
Two times on Rett?
Read the 1st Dec Press Release again.
Then, realize that the pps is $8.71.
What does that mean?
Not many possibilities. Only one.
Yup, the market CERTAINLY thinks that he is either lying or hiding or twisting about the data. And he very likely is.
Frrol: My understanding of odd-ratio was correct -- its straightforward.
If X out of Y placebo patients, and A out of B treatment patients show improvement, then the odds ratio is (A/B)/(X/Y). Yes, it can range from 0 to infinity.
Thanks. Yes, I always had a little bit doubt of OR -- but didn't go to the trouble to reading up on it. Thanks for clarifying.
Thanks.
Actually, saying "85% chance that one can improve over placebo" is very meaningful.
But, OR says something else -- its says "if x patients improved on placebo, then 1.85x improved on treatment" (here, improvement is defined by say -3.5 on adcs-all).
The first statement is very meaningful. The second statement (OR) has much less meaning because x can be very low. And, if x is high, it doesn't say much either.
How do we know that? (wrt ADCS-ADL measure)
we do know that the "others" ON AVERAGE did no worse than placebo
Why OR is a terrible measure.
Consider an example of a drug and disease, wherein (1) no person improves on placebo, (2) 10% of treated-people improve, and (3) 90% of treated-people deteriorate much more than placebo.
Wanna guess what the odds-ratio will be? It can be arbitrary high because of (1).
Should FDA approve such a drug, or even look at the odd-ratio measure? No, absolutely not -- and the OR really doesn't mean anything. The company needs to design a new trial focussing on the 10%-type of patients (in some sense, OR is a sub-group/adhoc analysis).
Let me give you another concrete example from Sarepta, since I know the case so well. In Sarepta's Etep trial of 12 boys, 2 of the boys lost their ambulation RIGHT AFTER the trial start. Since the drug was only for ambulatory patients, Sarepta excluded these 2 patients in their functional-benefit analysis -- since it argued that these 2 boys lost ambulation even before the drug had a chance to work. FDA never accepted that -- since you can never preclude the possibility that the drug harmed those 2 patients and caused the patients to lose ambulation. (Eventually, FDA approved based on the biomarker expression -- wherein exclusion of these 2 patients was less relevant).