Hi Doc:
Thanks for the response. I wonder whether you had a chance to review my earlier post addressed to you regarding certain anomalies raised by the February 26, 2018 abstract I cited and which is referenced in the iHub message board intro.
By way of quick summary, the abstract provides a simple graphic that breaks down the M+/M- major groups into associated molecular sub-groups where M+ appears to be predominantly if not 100% pro-neural and M- predominantly made up of mesenchymal(MES), classical and neural. You will recall that results were very remarkable for M+ blended as per the JTM and updated at SNO. M+ is not as aggressive as M- appears to be(with MES included in this categorisation) and appears to have characteristics associated with pro-neural which, in fact, the abstract categories as being composed of pro-neural. This is in contradistinction to earlier UCLA studies that found DV VAX to have little no effect on pro-neural. Further, these earlier studies found that the vaccine was particularly effective on the most aggressive sub-molecular group, MES. The reason was that MES is more immunogenic(like, for example, melanoma)meaning a greater residual level of T cells which DC VAX boosts and a relatively lesser immunosuppressive micro-tumour environment allowing the T cells more time to infiltrate before immunosuppressive brakes are applied. I don't know the extent to which MES MGMT methylation is as a proportion of overall MES but I suspect that it is rather small especially when considering that the abstract considers M+ being at least predominantly composed of pro-neural. In any event, MES mgmt methylated would have two pathways: immunogenic as well as cell repair interference which could imply at least sustained remission if not an overall cure. The abstract also went on to say that ndGBM is 50% characterised by EGFr over-expression/mutation and is also a molecular group included in M- as classical. The blended results for this M- group as shown in the JTM were remarkable with a delta of 7 months between SOC median and blended(from surgery). At OS36, M-survival, though, was only 14.3% (as per updated SNO). This truncated survival for M-, as a whole, could mask superior remarkable longevity of MES due to the fact that the vaccine may have relatively lesser effect on classical, thus a more abbreviated survival percentage at OS 36 as well as blended median survival which is a large percentage of overall ndGBM just like MES(reported to be anywhere between 25%~45% of all ndGBM).
I believe that LL's earlier findings on the vaccine's efficacy on MES included ALL MES and not just methylated which I believe is a relatively small proportion as explained herein above.
If the abstract cited is accurate, this bodes extremely well for DC VAX as it appears to be very efficacious for M+(pro-neural and 40% of trial ITT and 45% of overall categorised group--N=293) and a significant percentage of M- due to MES. This would cover at least 50% of all ndGBM!
In addition, I made reference to PFS and the possibility that DC VAX L has the effect of slowing progression as time unfolds and the vaccine begins to manifest its growing strength thus enabling increased overall survival even though there may not be at least an SS advantage in delta between SOC and Tx. I hope that the revised SAP addresses this possibility.
I also made reference to possible lack of SS wrt Tx and control(including x-over) for OS and that this is not necessarily bad in that it could show efficacy even for "late" vaccinations. Personally, I believe that there will be significant separation as you go out on the curves.
I ask again if you could review this and my previous post and provide your comments especially on the findings made by UCLA and subsequent findings I alluded to herein. Also with respect to what molecular sub-groups are in M-/M+. Are they as stated in the cited abstract or are they(or I) missing something?
Appreciate your response, Doc. BTW, very pleased by the Duffy hire. It is a great inflection point for me!
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