Replies to post #682576 on NorthWest Biotherapeutics Inc (NWBO)

[exwannabe]

Senti, take a look at table S3 when you draw up your timeline. My read of that differs from yours. I see tumors 4-8 maxing out around days 108-130.

[flipper44]

Senti, in the Car-t trial you are analyzing, when they say “all” tumors regressed (starting day 133), they were not talking about tumors 1, 2 or 3, I think. They believe those sites remained stable after 100% resection.

They are counting tumor stabilization to extend their 7.5 month “dramatic” response claim.

That makes this paragraph by them a bit disingenuous, because it lumps in stabilization with tumor response.

This dramatic clinical response was sustained for 7.5 months after the initiation of CAR T-cell therapy, and none of these initial tumors (tumors 1 through 7 and spinal tumors) recurred.

They are actually strictly talking about 4, 5, 6, 7 in addition to spinal tumor 8. They refer to “table S3”, and upon reviewing, only “tumors” 4, 5, 6, and 8 are discussed there.

I will bring up a peculiar anomaly. The mri and pet scan scheduled for day 156 (an important time) was cancelled due to lack of product?

The backdrop of this case report is that no other GBM patients that were in the 65 patient trial had a response.

I think your best argument is that the authors clearly overstated the length of response.

[flipper44]

Car-T study: Ok, finally, by the way, the authors concede that the reason Car-T likely failed in that patient is that tumors 9, 10, 11, etc, did not have cancer cells with the antigen the car-t was targeting.

In other words, in one of the 75% GBM patients, in a 65 patient trial*, tumor escape occurred within 7.5 months of car-t treatment initiation, two months of which included a complete response (in five tumors) before treatment failure via tumor escape.

The cause of this tumor recurrence is currently under investigation, with preliminary results suggesting decreased expression of IL13Ra2 (Fig. S8 in the Supplementary Appendix).

*no other GBM patients in that trial had a partial or complete response.