Replies to post #214468 on NorthWest Biotherapeutics Inc (NWBO)

[Umibe5690]

Correction: proneural is a component of M+ not M- as I have mis-typed.
Sorry for any confusion. Typing on iPhone is a challenge with fat fingers.

[longfellow95]

Umibe.
It is highly unlikely that the subjects in this trial have had tumor samples tested for transcriptional subclass. Such testing requires facilities only normally found in a specialised research lab.
One suspects that all the tumor material obtained from surgeries would have been used to create the lysate.

I hope, as indeed NWBO surely does, that the unblinded data will show benefit across the board, albeit to a greater degree with methylated. Certainly the TOP 100 data would suggest that this might be the case, with only 8% having the combination of all three main positive prognostic indicators.

[Doc logic]

Umibe5690,

Most of what I recall comes from Dr. Linda Liau's post mortum tumor sample analysis of earlier phase clinical trials and other research papers. Methylation has been noted to occur in mesenchymal but much more rarely. Early on, GBM research of biopsied or resected tumor tissue helped identify the prevalence of tumor genotypes and phenotypes. Once Dr. Liau realized how important utilizing all of the resected tissue was she stopped pushing for tissue for ID purposes so that important tumor antigens might not be missed in lysate preparation. I remember spending quite a bit of time early on to distinguish potential benefit based on groups like methylated MGMT and mesenchymal subgroup. Hyper methylated patients is also another small separate group that does well even with just SOC. I think these best performers are also highly likely to be pseudoprogressors, which are expected to do well with treatment and we're put in a separate group. So perhaps they were minimized by inclusion criteria so much in this trial, which seeks to mainly determine the impact of treatment on the middle group of patients, that they were not pointed out. The add in of pseudos at the end of the trial for analysis to get a look at the big picture is important because this group and unmethylated seem to be 2 reasons for mentioning home runs. Methylated MGMT patients are doing better too but appear to have a lesser percentage of improvement noted compared to historical than seen in unmethylated so far. Best wishes.