Replies to post #244198 on NorthWest Biotherapeutics Inc (NWBO)

[longfellow95]

Thank you Abeta. I am familiar with the data in the graphics you provided. These variances obviously contribute to the confusion. I guess the only way we will know, at least wrt to DC VAX L, is when the trial is unblinded and we get the full analysis. Hopefully these issues will be addressed by the analysis.

I doubt very much if they will. The only biomarker readout we will get is meth v unmeth.
As I've said before, I doubt very much if molecular subgroups were even tested in this trial.
Perhaps Cognate has the facility to do such a test, but I don't even know about that.

Such molecular profiling of newly diagnosed GBM patients is simply not routinely undertaken anywhere in the world.
It is only done in research labs using genomic analysis of cell lines from long dead GBM patients.

What would be the advantage in so doing anyway?
I think the whole 'L works best with mesenchymal' hypothesis is really rather overstated on this Board.
I only believe that theory, if you make the important addition of 'compared to other therapies'..
If one really believed that L worked best with mesenchymal per se, it might imply that L should be optimally given at recurrence rather than at first diagnosis, when the tumor has shifted to mesenchymal...
Is anybody really suggesting that?

My working hypothesis goes no further than believing L can still be effective at recurrence by which time the tumor has usually become mesenchymal, whereas other therapies basically can't.
Witness Kat and the Canadian chap who derived long term survival benefit after 1 or more recurrences.

The original research by Liau and Prins that concluded that L could significantly extend survival for mesenchymal, involved just a handful of patients, and that small sample is further complicated by the adjuvant booster issue (some patients received Imiquimod or Poly ICLC at time of injection and others didn't) and the fact that that study did not control for methylation status (at least it went unreported).

And methylation status remains the no.1 consistent and reliable prognostic indicator (as seen in our interim results).
Behind that comes IDH status. And all or very nearly all primary GBM's are IDH wildtype anyway.
And nowhere did Liau and Prins state or even suggest that L couldn't extend survival in other molecular subgroups.

The molecular profiling research is extremely interesting.
And does have significant future implications.
With the emphasis on future.
One of Abeta's links suggests that TMZ really only works with 'classical'; 20-25% of all GBM's.
But those sorts of conclusions are really very provisional.

So, their BLA if and when it comes is likely to be for all of ndGBM. And very reasonably so. (Unless the data shows that there is no treatment advantage for unmeth, which is unlikely, imo.)

This table from that Liau/Prins piece of research is important; in as much as people shouldn't draw too many firm conclusions from it!

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071163/table/T1/

From:-

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071163/


My opinion