NorthWest Biotherapeutics Inc (NWBO)

[sentiment_stocks]

Thanks for the response Avii.

So with the example you cite for Cel-Sci, they received a recommendation to close the study, didn't inform the FDA, the FDA found out, complained in a letter, and then Cel-Sci responded and told the FDA the reason they didn't inform them was because they felt they had no obligation to report this recommendation. Then Cel-Sci put all that into their 10-K.

NWBO has not indicated that they withheld any such DMC recommendation in any public filings, so IF the DMC made the recommendation, then the FDA was also informed. And we agree, the company would likely not have accepted such a recommendation from the DMC. So the only one with the power to halt the trial would be one of regulatory agencies. As noted in their usual risk language:

Our clinical trials may be suspended at any time for a number of reasons. For example, we may voluntarily suspend or terminate our clinical trials if at any time we believe that they present an unacceptable risk to the clinical trial patients. In addition, the FDA or other regulatory agencies may order the temporary or permanent discontinuation of our clinical trials at any time if they believe that the clinical trials are not being conducted in accordance with applicable regulatory requirements or that they present an unacceptable safety risk to the clinical trial patients.

Administering any product candidate to humans may produce undesirable side effects. These side effects could interrupt, delay or halt clinical trials of our product candidates and could result in the FDA or other regulatory authorities denying further development or approval of our product candidates for any or all targeted indications. Ultimately, some or all of our product candidates may prove to be unsafe for human use. Moreover, we could be subject to significant liability if any volunteer or patient suffers, or appears to suffer, adverse health effects as a result of participating in our clinical trials.

And then their 2016 10-K indicated that it was the FDA that lifted its hold in February 2017... pretty much making it clear that it was the FDA put the hold on, otherwise, how could the FDA lift it?

In addition, our Phase III trial of DCVax-L was placed on a partial clinical hold for new screening for enrollment in 2015. Although the FDA lifted its hold in February 2017 as previously reported by the Company, the Company had already closed enrollment with 331 of the planned 348 patients. Since we did not enroll the last 17 of the planned 348 patients, this could adversely affect the statistical and other analyses of our Phase III trial results, and could make it more difficult to seek product approval or more likely that further trials could be required.

However, if the FDA had requested that the company to not enroll any more patients before they lifted the hold, don't you think the company would have been obligated to add that to their own 10-K language too?

Instead, the company stated they chose not to enroll any more patients because it would delay the trial too long in order to follow them. Then two months later, the FDA lifted the hold. To me it argues that instead, whatever point of contention that had caused the FDA to implement the screening halt was resolved. Kinda like period.

I think we should take them at their word:

However, at this point the Company believes that the potential benefits that could be obtained from enrolling the final 17 patients would not be worth the time it would take, as the process of re-starting and re-training the sites (including through Institutional Review Board renewals) for further enrollment would take months, followed by further months for the recruitment itself.

So IMO, it simply doesn't make sense that the FDA would lift a hold if first the company agreed not to enroll any more patients. It makes so much more sense that the FDA would just keep the hold in place to make sure they didn't enroll any more patients. Otherwise, what would be the point? You can't tell me it was to make it look like there was no longer a problem with the trial... when there really still was? I just don't see it. Besides, I would argue it would irritate the FDA if the company made it look like the FDA was in cahoots with NWBO to give this sort of impression.

Now if whatever issue existed to cause the FDA to put the halt on in the first place - and then subsequently decide to lift it a full year and a half later - especially when they act lickety-split on lifting holds when more favored pharmas kill people, how do you know that the reason the company has disclosed the reason right now is because it might cast the FDA in a bad light? If that were the case, rather than make all that nonsense public (for now), some might consider it a more strategic move to hold off and keep whatever happy relations that may have developed over the past two years of working closely with the FDA to sort out such a mess in place. That's at least a hypothetical worth considering.

You state:

The patients were not "living longer" than theorized in the new protocol).

I'm not sure what you mean by this statement?

Sure we can "theorize they were in turn disappearing" but (and here perhaps is our primary disagreement) there is nothing you can do to salvage the trial.

There are perhaps a myriad of ways that the trial could be salvaged, if PFS is not stat sig. However, you don't know if that is even the case. Perhaps signs were pointing in that direction in the summer of 2015, and perhaps it had nothing to do with what was happening.

But two and a half years have passed and so a lot could have happened to change that, if it even were the case.

Baranuuk (Bohsie) set out to prove that PFS would be stat sig in a Seeking Alpha paper, and then, however unprofessional bears may have found this, the company specifically noted we should pay attention to his findings in September 2017.

So... there could have been some cases of psPD. If it was caused by CRT (chemo/rad) then it would likely be present in both arms and so very likely not hurt the trial anyway (as confirmed by Dr. Cloughesy).

And if it was caused by DCVax, which LL and others have indicated does occur, then we don't know to what extent that it did. And so while it may have occurred, we don't know if it made it so PFS cannot demonstrate a measly 4 month difference between the two arms. And with a thorough blinded adjudication of those findings, they may likely have been able to salvage it. Again, their comments regarding Bohsie's paper strongly hint at a successful PFS finding, adjudication or not.

So if it were the case that PFS was leaning or was likely to be stat sig... why wouldn't they unblind and stop the trial if PFS was indicating a stat sig result right now? A good argument could be made that they are either wanting to support a request for AA based on PFS with strong supporting interim OS data from the blinded data (since 90% of the patients are on DCVax anyway) that is "anticipated", or that they are so close to completing the trial anyway based on OS that they have chosen to make their case for full approval.

While all dots lead to futility for you, they obviously do not for me. We'll have to agree to disagree and see what turns up - hopefully soon - to support each of our versions of the dots.

(and a respected poster here noted Furberg is no longer on the DSMB - another dot).

Oh that's right... I remember that. There could be any number of reasons he's no longer on the board, and they may not relate whatsoever to whether or not there is any alpha left to test OS, which the company claims is separately powered. Besides, there was still a lot more data to sort through if any recommendation came about in the summer of 2015 so how could they possibly determine that from what the data was showing two and a half years ago?