NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

OK, I'll try to make this clear. The following is to the best of my understanding or opinion.

1. The Journal states the 38 undiagnosed patients are due to being the earliest enrolled:

The MGMT gene promoter was methylated in 39.6% of patients (n?=?131) and unmethylated in 48.9% (n?=?162), with information not available for 11.5% (n?=?38; the missing data relates to the early patients enrolled a decade ago).

2. Senti, through diligent very eye-stressing work that required insight, graphic skills and sweat, determined that out of the 38 undiagnosed MGMT, only 1 (to possibly 3) made it beyond 36 months. Lykiri pointed this out.

3. Exwannabe states it's not that clear. He thinks the quote up above meant kinda sorta there was a relationship between undiagnosed and the first 38 enrolled. I disagree.

4. 38 a "decade ago" can also show that none of the first 38 lived that long as the KM curve only goes out to 88 months.

5. So we have three pieces of information that show the first 38 enrolled did not do well.

6. The premise to this, as posited by you, is that they were primarily MGMT unmethylated. We can't prove this but there must be a reason.

7. You pointed out the first 38 might be the reason the first 223 enrolled did not perform well.

8. As you already know, there are several reasons to believe the last 31 patients were only "randomized" to DCVax-L.

9. When I put the simple calculations together, the first 38 would have started the trial in deficit with only somewhere between 3% and 8% survival at 36 months.

10. The next 144, actually divided between methylated and unmethylated, had something more like 28% to 30% survival at 36 months.

11. Skipping the the next 79, the last 70 patients alive under 36 months should have no worse than 33% survival when they reach(ed) 36 months from surgery. This is determined by using Dr. Bosch's given event rate back at ASCO 2017. If the event rate continues to slow, which it sounds like from 2018 it very well may have, those 70 probably have a 39 (+)% survival at 36 months. The last 31 patients are likely all randomized to DCVax-L, and they may very well have a survival rate of 50% or more from surgery.

12. The thinking would be they knew too little to start the trial over in 2011, so they included the first 38 patients enrolled with unknown MGMT status. The next thing that happened is after they fixed the likely issues with enrolling 38 patients without MGMT diagnosis, the next large group of patients started living too long to get good separation statistics on.

13. After that the second half of the trial started including sicker patients, but from all appearances and calculations, in hindsight, many were living a long time too.

14. By this time, it may very well be the German's were saying something like, "hey, we can't keep giving some people placebo because it's pretty clear at this time that DCVax-L works." UCLA moved the expected primary completion date a full year from October 2015 to October 2016. In October 2016 they moved it to November, when shortly thereafter, they probably reached 248 PFS events.

15. It is not clear, but it seemed like they might have justified continuing the trial based upon the ethics that all control had already PFS evented. This was what it appeared to be in a slide presented from UCLA back in December 2016.

16. With no patient ethics issues, they still needed to obtain separation on overall survival at the 36 month mark definitively. Without it, countries like France and Great Britain would not consider the intrinsic value for DCVax-L.

17. The likely trial ending trigger point, already moved from October 2015 to October 2015 to November 2016 to Summer 2017, was again moved to (via nice timeline provided by NWBO) summer 2018. The end of the active study period for patients.