NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

The 30% intraday drop was the day following Dr. Liau's October 15, 2015 presentation. After I learned about the presentation, long after the fact, it is my assumption that hedge funds took home the wrong message. They thought it was an admission the trial was failing because of the crossover.

To assume Dr. Bosch just yesterday somehow indirectly told us the results of the first interim analysis for the phase III trial is also the wrong take home message -- or rather, just plain wrong.

However, I will agree that the longer this goes on, the more every poster can come to any speculative conclusion they want to.

For now, here is what I think.

1. All (meaning on average) patients within the main group of the phase III DCVax-L trial are living longer than expected, and Dr. Liau has the highest standard for what overall survival she expects. (aka: 24 months)

2. It looks like the 149ers had it right, and the first interim for PFS had not occurred by October 15, 2015.

3. The trial was still blinded on October 15, 2015.

4. The double progressors survived a median of 15.3 months, and beat SOC historical by 5 to 7 months.

5. Dr. Bosch and Dr. Liau have been inferring all along that pseudoprogressors respond well to DCVax-L. They should know; because, NWBO has an expanded use group that is completely unblinded (in addition to the one patient in their information group, plus hospital exemption patients), and it has a significant number of pseudo progressives. They likely just 'keep on keeping on' when on DCVax-L the phase III protocol.

Pseudoprogressors, as Dr. Liau pointed out in her presentation, almost never progress when they live very long periods of time. So it would be very difficult with a group of 32 patients, 10(or 11) of which are placebo/soc, to even get results on all but a couple SOC PFS by this time. In other words, all one could do is compare the whole group with historical standard of care and perhaps some from the phase II UCLA trial....otherwise no data, and just think how long they'd have to wait with a crossover.

6. "Might" was the critical word during Dr. Bosch's presentation, and it's true, pseudo-progression patients respond to SOC/Placebo and SOC/DCVax-L early on. It will be the longest group to determine PFS advantage (if any) over crossover, and they may never determine OS advantage, because most patients simply keep living.

7. Conclusion.

Dr. Liau knows "all" patients seem to be living longer than expected, it appears, IMHO, all patients are eventing slower than expected as well -- from thinking long and hard about the little amount she shared. The placebo, unlike in the IMUC trial, is not active.

Let's suppose, for the sake of argument Dr. Bosch (it's now 3.5 months later past Dr.Liau's presentation) knows the PFS results (which I don't think he does), he would not use the word "might" unless there was a possibility that a fair minded FDA distilling through the information carefully could find, allowing for pseudo-progression distinctions, for accelerated approval. Furthermore, to make that distinction, I do not believe the FDA would ignore immune response, (RK found this from the old protocol):

ENDPOINT: Immunostimulatory response (yes or no). A patient will be
considered a responder if one of the following conditions holds at least one time
point in the study: a) T cell proliferative response to DCVax-L shows a stimulation
index of 2 or greater, b) a greater than 3-fold increase in CD8+ cells staining with
tumor antigen tetramers.

I agree with Evaluate, that alternative endpoints are Dr. Padzur's specialty, and he has come full circle at the FDA. The early brilliance that led him to be hired at the FDA, his theories on alternative endpoints; now, mostly because of increased safety and durability of many vaccines/immunotherapies, will/should allow the FDA to make exactly what we as humans need at this time.

If we can't adapt to what science throws our way due to human Intransigence, we may ultimately fail as a species.

Yeah, I think it's that big of a deal.