NorthWest Biotherapeutics Inc (NWBO)

[sentiment_stocks]

Thanks for responding... I honestly did want to get your take.

Regarding A) Tumors 4,5,6 and 7.
In the article, the authors state,

While the IL13BB?–CAR T cells were being manufactured, the patient participated in an investigational clinical trial (ClinicalTrials.gov number, NCT01975701) at a different institution (Fig. S2A in the Supplementary Appendix). However, the disease progressed rapidly during treatment, with the development of multifocal leptomeningeal glioblastoma involving both cerebral hemispheres (Figs. S3 and S4 in the Supplementary Appendix).

You can see from the visual below (which is Fig. S4), that it includes tumors 4, 5, 6, 7. The notes listed in the visual above indicates the location of the T1 - T5, although in the notes, there's no indication that 4 and 5 are new, and while they note that 6 and 7 are new, there is NO indication that T8 is new (which was really what I was primarily focused on). Still, you are right that the authors do note that 6 and 7 are new. But it does seem like the authors are trying to push a narrative that tumors 4, 5, and 8 were all there previously (especially with T8).


Regarding the quote that you cited, they do cite that all of those tumors progressed, but they do not indicate that 4 and 5 were new, only that 6 and 7 were.

During the six weekly intracavitary infusions (cycles 1 through 6) (Figure 1A), the treated tumor in the temporal–occipital region (tumor 1) remained stable for more than 45 days after surgery without evidence of disease progression (Figure 1B). However, MRI revealed that nonresected tumors in the left temporal lobe (tumors 4 and 5) and new tumors (tumors 6 and 7) near the resected lesions 2 and 3 were progressing (Figure 1B).

Response duration:
We agree that the response began around Day 130 (I had Day 133) and that by Day 190, all the tumors (when combined) had decreased by 77 to 100%, which is great. But between Day 190 and Day 228, four new tumors were present. And you can see from Figure 2A on the Intraventricular Car T-Cell Doses schedule that no MRI was done until Day 233 (although the article notes that the four new tumors were found at Day 228).

Unfortunately, this patient’s disease eventually recurred after cycle 16 (228 days after the first CAR T-cell treatment) at four new locations that were distinct and nonadjacent to tumors 1 through 7 and the spinal tumors.

So while tumors 1-8 either did not return or were reduced significantly, which is arguably very good, four new ones were growing - surely even before Day 228 or Day 233 when they were quite visible on the MRI. Had an MRI been done earlier, one could hardly argue that this was a complete response lasting 5 months, and really, even the two months I'd argued is questionable, given that four more were growing during that time between Day 190 and Day 228. I guess you could say that the CR was 5 months for the older tumors, but with 4 new ones growing, how could that count as a CR or even as no progression?

The mystery spinal lesion (#8)
So it seems we agree, somewhat, that this tumor showed up after the initiation of Car-T. It certainly seems as if the authors do not want to cite it as "new".
"Or maybe they carbon dated it" - haha... :)

Thanks for giving me your take. Feel free to respond to what I've written here as I do value your opinion, on this topic. :)