NorthWest Biotherapeutics Inc (NWBO)

[Pyrrhonian]

Appreciate the candor. I would only say that the response to my developing viewpoint on Direct is skewed (bias will do that). It has always been in flux, and I've pointed out how early any signals of efficacy were and that the therapy has a long ways to go. Have I really done an about face?

I remember flipper arguing that Direct would replace L and all surgical procedures with it (he probably still thinks this), and I had to disagree. He left the board for a while, though as usual continued to pm everybody, and some people blamed me for it. Guess I was too "mean." Was I really pro-Direct then?

I was more hopeful about Direct before, sure, but of course we didn't have much data to look at. Just Triozzi and.. well, just Triozzi! In theory the same response rates should have been seen here, but the body is just more complex than that, and intra-organal tumors are just tough to eliminate.

Checkpoint inhibitors (CI) allow t-cells to do what they are naturally capable of doing but because of the immunosuppressive microenvironment of the tumor are unable to do. What happens when one of these patients responds to the therapy? In under 2 months the t-cells dissolve their tumors. Some 40%, some 70% and some over 90%. Gone. These tumor cells "burst" from the t-cell activity. They don't just die and sit there (that's cytokines doing that). What we are seeing here with Direct is a different thing.

I'm not saying Direct won't show a clinical benefit (prove overall survival (OS) benefit)--I actually think that is more likely than not, but it will be a while before that could be shown in a study and given weight. You need a concurrent control group, preferably given a placebo, to make a survival claim and have the market and health community take it seriously. So, that's just a ways off for Direct (a number of years).

Now, do I think in the Ph II leg they can show some ORR? Maybe, considering they will inject more than one target lesion with more frequent injects, and the patients overall will have more robust immune systems (see criteria). I could see it happening. Particularly in sarcoma (whose tumor cells may respond differently to Direct's induced cytokine storm). But how far away is that? Probably more than a year from now. And knowing what I know about fickle, "give me it now" retail investors, plus multiple raises=dilutions, I'm not expecting this high of a market cap between now and then (unless by some miracle the Ph III is halted at first interim).

I have and continue to like DCVax-L, and think it will meet stat sig in it's Ph III trial.