NorthWest Biotherapeutics Inc (NWBO)

[Pyrrhonian]

Hi Doc. Something I wrote a while ago:

"I read some debate as to why now no mention of method A vs B. I think the most entertaining apologetic is that the company does not want to hurt the feelings of those who would suspect they were given Method A and not B, even though no one has gotten any DCVax Direct injection in quite some time now. These 39 have been long done.

So if that is spurious, why no longer mention it? And this doesn't just apply to Linda P's talk but also they removed the mention of "two different activation methods used" in the list of variables in slide 19. It's completely gone now.

Well, knowing a bit about these this management team's public relations campaign tactics, I think the most logical reason is that as data matured, method B no longer looked as compelling compared with A. And possibly also they realized (with all of the lawsuits coming at them) that they may want to be more careful with misleading statements.

If the protocol change occurred sometime part way through enrollment whereby they accepted ECOG 0 and 1 patients only and stopped accepting ECOG 2, and perhaps allowed more stage III patients than stage IV, and according to batch manufacturing practices used Method A for the first half of patients and then Method B for the latter half, then the Method B patients would of course have the better prognoses. So trying to draw a comparison between the two as equal groups would be inaccurate.

But even still, let's assume they don't care about that, the main reason then become the numbers no longer flatter meB vs meA so well.

The Feb update showed 50% of meA patients were still alive and 86% of meB were still alive. But what wasn't disclosed was the range of each group's survival. Of course if half of the patients were treated with meA, and then the back half treated with meB, that would mean the range as of Feb 2015 of those still alive would be 13-18+ months for meA and 9-13 months for meB. Well, then once those of meB reached the 13-18 month range their % alive would definitely be below 86%. I have perhaps figured out the range and % alive for each method assuming the first 18 enrolled were given meA and the latter 22 were given meB (18 vs 22 meA vs meB are number NWBO supplied before):

-9/18 patients given meA were still alive in Feb 2015 from 13-18+ months.
-18/22 (which is 82% of all meB, 86% of those evaluable) patients given meB were still alive in Feb 2015 from 9-13 months.
-12 patients had died at 9 months or less in Feb 2015
-Therefore as of Sept 2015, of the additional 8 that died (20 total), 6/8 were meB patients (passed at 13.5 months or earlier) and 2/8 could have been meA or meB (passed at 16 and 18 months). The one who passed at 18 months could have been meB because a number of the 13 month survivors were meB under the above scenario in Feb and that was 7 months ago.
-Theoretically all 8/8 who died since Feb could be meB, but 6/8 must be.

Therefore:

-if 6/8 who died are meB, the breakdown is 7/18 meA or 40% still alive and 12/21 meB or 57% still alive
-if 7/8 who died are meB, the breakdown is 8/18 meA or 45% still alive and 11/21 meB or 52% still alive
-if 8/8 who died are meB, the breakdown is 9/18 meA or 50% still alive and 10/21 meB or 47% still alive

I think that says it all for why meB vs meA distinctions disappeared. Data no longer flattering."


Also I think meB was just their super duper awesome patented method of GM-CSF alone with no IL-4 and meA was the normal diff of PBMC into DC via the standard GM-CSF + IL-4. Probably now meB looks similar to meA, or not different enough to mention it anymore in a special slide. This is a great example of how NWBO pumps data. They only mention what can be made to look flattering and ignore all else. Then if something changes and that thing is too difficult to make look flattering they simply drop it.

Ps, They stopped accepting ECOG 2 around 6-20-2014:

https://clinicaltrials.gov/archive/NCT01882946/2014_06_20/changes

increased karnofsky from >60 to >70 too.

GL out there.