Replies to post #132950 on NorthWest Biotherapeutics Inc (NWBO)

[dpinvest]

That explanation makes sense, thanks. So tempting to add shares, but the management story remains so strange.

[sentiment_stocks]

Thanks for your analysis Dan. If the following were the case, do you have any ideas as to what or who would have brought this issue...

that the trial may not be an "Adequate and Well-Controlled (AWC) trial

...to the attention of the FDA;
thereby causing them to then implement a screening halt?

The reason for the nagging question regarding the hold of screening may be simply the FDA's question about whether the trial had been an Adequate and well-controlled (AWC) trial raised in Summer 2015, after "once again" change in screening conditions in Germany, thus the hold of new screening.

[flipper44]

Dan, kind of similar to my final theory for the halt I gave back in December of last year.

My final speculation on the partial halt.

I have strongly persuaded myself at least, LOL, that the remaining 17 enrollment spaces were specifically intended to be used if a human equivalency study had been needed for commercial production approval.

Now back up.

If that is true, there is no way in Hades, if I had been CEO, that I would have explained that uncertainty along the way to shareholders until the issue was either resolved or became moot. Both to protect trial integrity and to allow uninterrupted discussion between CROs and NWBO.

Anyway, if I'm correct, it tells us the trial did not randomly end on 331, instead 331 was written into the protocol to stop enrollment exactly at that point unless a human equivalency study was required for commercial manufacturing approval. It's a very proactive trial if that was the case. NW said the halt was part of trial protocol. Since the new trial protocol was written, they apparently planned all along to have 75% events of 331 enrollment to complete this trial regarding the primary endpoint, with one caveat.... -- under this hypothesis.

So, under this possibility, what does it tell us when they say they are not going to enroll those 17 enrollment spaces?

To me it means they either demonstrated equivalency for commercial manufacturing, or they have decided human equivalency can't be done within the trial at this point because the trial is too far along to add more patients, or what I think, commercial manufacturing is approaching approval, but the trial, for better or worse, will not be used for any human equivalency study.

In other words, I think the screening partial halt was because they effectively reached full enrollment (aka: enough patients in the pipeline to get there) but for any possible requirement that a human equivalency study was needed, actual enrollment was reached October 30, 2015, imho, according to clinical trials.gov.

This trial is old, and as I once speculated, the regulators probably wanted to make certain NWBO was working promptly toward proving commercial production viability, which is one of the hallmarks/requirements of an adequate and well controlled study. My guess is whether they rely on new legislation (more than just the Cure's Act), or regulators ultimately directly approve commercial viability, this will shorten the time to approval by at least a year. I think, imho, commercial validity is sewn up if trial results demonstrate to be approvable, otherwise regulators would have required 17 additional enrollees for an equivalency study quite some time ago.

[Astavakra]

This is an interesting theory, but I have one problem with it. Paraphrasing a comment made by Linda Powers after the halt was made public, she basically said, 'They're trying to turn good news into bad.' I can't make a connection between that comment and your tempting theory. Can you or anyone?
A theory that I'm more comfortable with is that either the DMC or some member thereof or the FDA saw what appeared to be an unusual amount of early progression and concluded that that meant failure of PFS. This would be the bad news. What the company were aware, and becoming more and more convinced of due to numerous data that were becoming available, was that immunotherapy can and often does cause inflammation of the tumor due to necrotic tumor tissue, infiltration of T-cells, etc., and that inflammation causes imaging to show an increase in tumor mass which would, according to measures established for SOC, otherwise indicate progression. This would be the good news. Inflammation=immune response. Wouldn't DMC be aware of this? Perhaps, but if the protocol was written in such a way (remember, it was created a few years before this time when a lot less was know of the effects of immunotherapy) that mandated assessment of tumor growth via imaging, then inflammation (i.e., immune response) would be reported as progression of the disease.

I know that there are differing opinions regarding the incidence of apparent pseudo-progression due to DCVax. That there are significant numbers of cases of treatment-induced enlargement is my conclusion.
And, getting back to Linda's comment from that time, I find it interesting wording. I am fairly certain that she said, 'They're trying to turn" good news into bad. Who are They? And, if they are trying, doesn't that mean some intentional activity? The question remains open. However....