NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

Thanks AVII. Interesting paper on Audencel. It's too bad they didn't have some separation, but what can we learn from it? I admittedly read the paper a little fast, but it was a predictable trial.

1. They used maturation agents that have been known to cause stronger pseudoprogression -- or whatever you want to deem it when it is caused by the DC response. It is not surprising then if they misdiagnosed many patients and stopped treatment.

2. They injected into the node, which, unfortunately, does not allow the natural final dendritic migration activation. (A nerdy aside, it is ironic, imo, the move from London to Sawston is labeled a "migration." The parallels to dendritic cell "migration" are striking. Particularly with regard to the lead resource they had/have in London.) Anyway, the migration in trains of DCs to the node, as opposed to being airdropped into central station, was visually captured by other scientists in other settings. The DCs literally change their morphology on route. This natural preparation during migration for eventual expression and costimulation is likely one of many attributes that helps set DCVax-L apart.

3. Audencel did not adapt their manufacturing approach during the trial and/or convert from one phase to another to allow this. This is, arguably, an antiquated way to develop biotherapeutics, particularly if you have, like NWBO, many patents and manufacturing improvements waiting in the wings. For this and many other reasons, I believe there was at minimum, one manufacturing change in the DCVax-L trial at conversion into phase III, then perhaps one or two important manufacturing improvements to enhance product consistency thereafter.