Replies to post #293141 on NorthWest Biotherapeutics Inc (NWBO)

[Doc logic]

Lykiri,

Really good find! I have said for a while that I believed that the wait we have endured is at least partially related to comparing German data with data from the rest of the trial. I came to the conclusion that the Germans became convinced that at least the low absolute lymphocyte patients were responding, perhaps with pseudoprogression, and then perhaps finding total clearing of the tumor in some of the patients. Since patients were not being screened by tumor subtype, and certain subtypes were perhaps obviously responding very well, then the Germans would not allow any SOC/placebo patients into the trial knowing that a statistically significant correlation existed. Is it just a coincidence that IDH-1 status has been added in at the end of this trial or that mesenchymal patients might tend to do better than normal? The science tells me no and the "screening hold" might just be in support of the science ie good news turned into bad. Best wishes.

[flipper44]

Gem. Thanks.

[sukus]

Aha. This is one point of heated disagreements between longs and naysayers that caused the price to drop precipitously. Glad that happened and accepted in Europe. I believe cell cultures machines are still improving as we speak. 5 years latter who knows the machines are much sophisticated than today’s technology. Are DCVax going to be stuck with old machines? No right?

[exwannabe]

Yes, Bluebird did overcome a late process change. I was discussed with RAs years ago. It was disclosed to the public and came with post approval / pre-launch requirements. The launch was delayed about a year for this.

https://www.fiercepharma.com/manufacturing/bluebird-bio-s-delays-zynteglo-launch-as-manufacturing-trips-up-another-gene-therapy

OTOH, you have MNKD and DSCO which faced many years and additional trials on this type change.

So agree that changes are possible, but do carry risks.

[flipper44]

Lyriki, one of the possible alternatives myself and a few others tossed around some years ago was that the last 31 were being used as a bridge study to possibly confirm any optimized manufacturing process. Your find shows how such a methodology was publicly accomplished with another company. One of the clues that might lead us to this speculation with NWBO was the attention drawn once 300 patients were enrolled. Another clue was the attention drawn to the German optimization and previously to the patent improvements (example: tangential flow filtration) that one would be hard pressed not to incorporate over this length of time. Another clue was the further partial enclosure of steps in the process along with companies that helped Cognate keep the blood chain supply completely enclosed. Anyway, there were many more possible clues that made it a reasonable possibility. Many years ago Dr. Boynton was hopeful they could wait on any manufacturing optimization (because of the delay it might cause), but it’s reasonable to guess that perhaps they didn’t wait to place optimization into the mix.

If that group was not randomized, and they did somewhat better than the earlier treatment patients, it is easy to see why NWBO would also need historical comparisons (as well as trial comparisons) as part of the narrative.