NorthWest Biotherapeutics Inc (NWBO)

[meirluc]

1. I need to wait for the published results on mPFS. It doesn’t make sense to me to have a vast improvement in mOS without a corresponding improvement in mPFS. If the GBM dynamics under DCVax-L is according to the model you suggested, then mOS should be the primary and possibly the only endpoint, imo. The team should have a dynamicist who should model the progression under DCVax-L administration. It is not essential, but at least that would be interesting to me.

There is a possibility that the unblinded treatment mPFS and mOS will be statistically significantly better than the mPFS and mOS of the placebo/control arm. However, I will not bet on it. Remember that the blinded and blended post surgical mOS was only 23.1 months and we have to subtract about 3 months from that to obtain the post enrollment mOS. That is not a great result and may also be reflected by the mPFS of treatment vs. placebo/control which may or may not show SS differences favoring the treatment arm.

Having said that, there is little doubt in my mind that 25%PFS and 25%OS for the treatment arm are home runs in that they will be impressive on their own as well as significantly better than placebo/control.

Remember that according to the report of February 2017, roughly 36 months after the midpoint surgery and 33 months after midpoint enrollment, about 25% of the trial was still PFS. I have not come across trials with a similar GBM population where 1/4 of the trial still demonstrated PFS after 33 months post enrollment. I will also not be surprised if 25% of the treatment arm will still be alive beyond 4 years and more than 20% survive past the 5 year timeline.

I believe that in this trial it is all about the tail and the mOS and mPFS will not have great significance. The importance of a long thick surviving tail may have forced NWBO to compose a new, hitherto unconventional SAP which may explain why it has been taking over 6 months to do just that.