NorthWest Biotherapeutics Inc (NWBO)

[meirluc]

Thank you HyGro for the article which I will reread again more thoroughly.

However, I do have some initial comments..

1. The authors comment that no other study has abandoned the primary endpoint is meaningless because no other study had used after radiochemotherapy (that can also cause pseudoprogression), an agent like DCVax-L which unexpectedly also frequently caused pseudoprogression. Therefore, none of the other trials had to scrap their PFS as the primary endpoint because their treatments did not cause a second unexpected PsPD.

2. I never read that tbe DCVax-L trial was limited to patients with tumors in only one hemisphere.

3. The orthodox exclusion of rapid progressors in the DCVax-L trial while perhaps more extensive than the exclusion of rapid progressors in the comparator trials, was matched by a more extensive exclusion of radiochemotherapy induced pseudo progressors in the L trial than was the case in the ECA trials. The overall result of those exclusions was a wash and that is shown by the almost equal mOS results of the unmethylated GBM patients in the DCVax-L and ECA trials.

4. Despite the fact that the DCVax-L trial did not differ from the ECAs with respect to the mOS of unmethylated GBM patients, demonstrating an absence of cherry picking in the DCVax-L trial, the methylated GBM patients in the DCVax-L trial had a far superior survival record than the methylated GBM patients in the ECAs. This can only be due to the ability of DCVax-L to increase longevity of methylated GBM patients.

5. How can one explain that in the DCVax-l trial, the 92 patients that included 64 crossover patients but also the remaining 29 patients who never received DCVax-L, had a combined mOS of about 24 months. With no real difference effected by the trial exclusion of the DCVax-L and the ECAs trials (witness the unmethylated GBM results), the only reason for the survival capacity of those 92 patients is DCVax-L.

6. Despite the similar mOS of the unmethylated GBM patients in the DCVax-L and ECA trials, an unexpected 8 of 131 unmethylated GBM patients in the DCVax-L trial (6.1%) survived 5(+) years whereas very few if any unmethylated GBM patients in the ECAs, were in that category.