Replies to post #471132 on NorthWest Biotherapeutics Inc (NWBO)

[Hansm7777]

Love Love Love it FeMike !!!!! Lets get it stickied on the wall. Great Job.
Thank you,

[Red_Right_Hand]

great explanation, thanks!

[Mionaer1]

Chapeau Mike. Well done!

[exwannabe]

#1. PFS failed

I have no issue with the position that PFS failure did not indicate DCVAax-L did not work. Hell, AVII77 said it would be a reason to suspect it DID work.

#2 Endpoints changed post hoc

You think being changed prior to unblinding makes it OK. Wrong. What is an issue is changing them based on information from the trial. And that did happen as NWBO knew whatever went down in 2015 and almost certainly that meant they knew PFS failed.

#3 The RAs will not allow ECAs

They will allow ECAs. No argument. But they require a lot of care to be defined and executed well. In addition to the above consider this. One key in a trial DESIGNED for ECAs is patient selection. In randomized trials, one can do what they want. But for ECAs, they must be careful to allow a match.

In this trial, they only enrolled patients with intent for near complete resection. The comparisons did not match that, and it is a very real factor.

#4 Trial treatment vs placebo

The OS in the blended population was better than the OS in the treatment population. You can spin as much as you want, but that is simple and clear.

[Sojourner55]

Mike, great job !

[hoffmann6383]

Appreciate the explanations Mike. #4 is what I found most interesting as I also didn't quite wrap my head around it at first. So, what you are saying is that the misleading bear argument is including cross over patients in their survival numbers and thus these are not true placebo (SoC) patients?

[CrashOverride]

Knocked them out of their first class seat!

[pgsd]

Thanks for sharing.

[chees]

Self-proclaimed biotech guru still doesn't understand by 2018 the trial became virtually single arm trial, yet this random bear argument is succesful in creating fear.
What a world we are living in !

[ilovetech]

Love it. But would it hurt to have the company do a fraction of what investors do to debunk FUD, as quickly and as thoroughly?

I just don't understand the lag? Amarin was famous for this. After every bear - crickets. If it's too tough get someone else.

Jeez
ILT

[Nonlinear]

Regarding Bear Argument #4:

Another explanation for the reduction in percentage for the 36 months survival is that the Kaplan-Meier curve (2018 publication) does not represent all 331 patients.
About 64 patients in that plot are censored meaning the were either lost to follow up (small number) or had not yet evented (majority of the 64).
If those 64 had a worse prognosis (outcome) than the other 267 that were represented in the 2018 Kaplan-Meier curve and were part of the treatment arm then consequently the survival percentage would be lower in the 2022 Kaplan-Meier curve.

[extrooper]

Great job Mike! How is it that you are so well versed in this topic? It is like you wrote the book.

[sentiment_stocks]

Brilliant, Iron Mike… thank you for posting that!

[sukus]

Wow. You answered the most difficult question from the presentation. The short took the opportunity to do what they did best. But you had provided the answer why that happened. I guess now longs and shorts have enough to digest. And on point #4, it is just simply amazing. Suddenly wow two birds with one stone? Never occurred to me that this vaccines would work for placebo patients that crossed over. Simply amazing creative out of the box deduction. Thanks Mike.

[extrooper]

This needs to be pinned to show truth.

[dennisdave]

Thank you Femike

Okay, so here we have an estimated 36 month survival rate of the placebo group of 34%! Wow. This particular individual even made a joke about this, saying maybe they should be running a trial on whatever placebo this is. Haha. It's funny, because it's ridiculous. A placebo is not going to boost survival that much, obviously. This was my first tip that something isn't adding up. So let's back calculate where these numbers came from.

Placebo in GBM cancer is utterly meaningless. Shorts should first prove that in any GBM trial placebo did anything better than SOC ever. We know from other biotech trials such as for rheumatism and depression drugs that the placebo effect play an important role and should be considered when calculating the outcome of the trial.

But not with GBM. So exwannabe please show me a GBM trial where placebo did anything to PFS or (m)OS. If you can prove that then you can make some sort of a point, but there isnt

[BWIS]

Great Mike. Did Clinical trials .gov ever show the updated SAP endpoints like overseas. If not then isn’t af correct that the primary endpoint is still pts?

[dmb2]

FeMike, agreed, the recurrent performance was very impressive and consistent with the strong performance against significant residual disease and when one considers that the vaccine was not refreshed by the recurrent tumor, the results were even more impressive. The level of knowledge that will be gained from this study is tremendous and the results across the board certainly give physicians and patients much more hope to combat this awful disease. The combination of DCVax-L against the original tumor and a recurrent tumor as needed appears to be a far superior set of tools than current SOC, The upcoming publication should add more clarity. Approval of DCVax-L for GBM is now in sight.

GLTA, much more to come here

[meirluc]

Outstanding post FeMike. A higher percentage of crossover patients than early DCVax-L recipients became post 3 year survivors (and probably post 5 year survivors). Yes, DCVax-L works for all patients.
Can't wait for this to be confirmed by the TLD and publication.
I am also very eager to see the results of the UCLA combo trial. I am wondering about the possible magnitude of life extension for recurrent GBM patients who after progressing are treated with their autologous vaccines which are directed against their mesenchymal antigens rich tumors. Also hoping that keytruda will be the icing on the cake.

[cfoofme]

Excellent summation Mike correcting massive misinformation. Bears may be out of winter hibernation but they continue to wander around half asleep.

[biotrade49]

First, one should point out to the bears that the 2 curves they are comparing are not the same. The data for the unblinded survival curve is plotted from date of surgery while the TLD survival curve is plotted from date of radomization.

[Cheesey12]

FeMike,

I’ve been waiting to read something like this. So thank you! This is a really important post I think most should read. Something just didn’t fit….about their argument. Now we know.

[biotrade49]

FeMike,

The other problem with Bear Argument #4: Placebo outperformed the treatment group is that they are comparing apples and oranges.

The 2018 paper measured survival from time of surgery while the TLD survival data was from time of radomization. If you cut out the 1st 3 months from the 2018 survival curve and slide the curve backwards to zero then you get a curve that declines much faster because during the 1st 3 months no one dies. This gives you a curve from 0-33 months. The trend is very well established at 33 months which allows you to extrapolate the curve out 3 months more to 36 months. This gives a 36 mo survival of ~20% (not 28%) for the entire population.

Whether, the Bears are knowingly being deceitful or just sloppy in their research is unknown.