Replies to post #214641 on NorthWest Biotherapeutics Inc (NWBO)

[longfellow95]

Umibe.
On the original reporting of the Liau study about a greater treatment advantage conferred to Mes patients, I viewed things similarly, even in terms of potential 'cure' for Mes patients. But research findings have moved on and diversified somewhat, I believe. And personally, I would never use 'cure' and GBM in the same sentence any more.
It has now been found that intra-tumoral heterogeneity sometimes exists, with different expression profiles existing within the same tumor.
Along with that, some research has indicated that certain treatments including RT and Bevacizumab can encourage a transition from one genetic profile to another, with the shift always being towards Mes.

I don't think methylation status is tied to proneural profile.
I think it is represented across all the profiles at least to some extent.
I don't know what graphic display you are referring to. I certainly haven't seen it in JTM.

There is though, an association between secondary gliomas, younger patients, IDH mutation, proneural profile and better outcome!
But 90% of GBM's are primary tumors.
Then you also have proliferative, as a fourth subgroup, mentioned by some and not by others.

At least one group have identified what they call molecular clusters, which they believe are more accurately predictive, than the previously proposed proneural, classical, and mesenchymal.


So all in all, I now view it as a much more complex and confusing field. And that I think is the nature of GBM. There are no simple, persisting intrinsic subgroups, excepting perhaps the IDH mutation/proneural link. But even with that there is the tendency towards a mes transition with certain treatments.

I believe that DCVax does have an 'across the board' benefit however, with the extent of benefit clearly greater with meth. Though we know that there are at least some unmeth patients in the 'TOP100'.
I think that is how NWBO sees it it, with the stress they have given to only a small minority in the TOP100, having all the favorable factors.

It is not only in GBM that biomarkers are imperfect.
The PDL-1 expression biomarker for ICI response for example is far from perfect.

http://cancerres.aacrjournals.org/content/69/23/9065.long

https://www.futuremedicine.com/doi/full/10.2217/fon.14.86

[Doc logic]

Umibe5690,

I think longfellow95 did a good job of explaining the current situation. IDH status carries a strong link as does methylated MGMT vs unmethylated MGMT patients, both of which seem to respond well to DCVax-L longer term. Unfortunately for investors the blended mOS of 23.1 months, which is very close to what Dr. Linda Liau said was a common mOS being seen in various trials in her October 2015 presentation, does not afford investors any great confidence in and of itself. The 28.2% living 3 years or more is the real hope that if combined with pseudoprogressors could push the envelope significantly on 4 and 5 year data and that would be very gladly welcomed. Best wishes.