Replies to post #359112 on NorthWest Biotherapeutics Inc (NWBO)

[Sojourner55]

Flipper, I think that's an astute observation.

Maybe it even explains Perlmutter/Frazier getting out while the gettings good. They knew the status of those confirmatory trials when they announced their intent to leave.

[ATLnsider]

I agree flipper44...

[flipper44]

It also might be a form of statistical revenge against CIs by the universe. Something myself and others discussed years ago was the fact that hundreds and hundreds of checkpoint inhibitor trials would eventually show stat sig in at least 5% of trials because that is the margin of error. The problem is that if you then subject those trials to follow up confirmation trials, any luck of the draw winners from the CI lottery would be exposed. These withdrawals may be statistical inevitability catching up with statistical gamesmanship/overload.

[eagle8]

Great post.
Thanks.

GLTU

[jondoeuk]

I think it does leave a gap, and agree with others this might intensify the need to utilize a safer and potentially more symbiotic therapy like autologous DCs.

There are a number of hurdles, such as immunosuppressive tumour microenvironments. Vaccines are simply unable to overcome them, while ACT has the potential to.

This year, AUTL will move AUTO6NG into the clinic. It is an anti-GD2 CAR-T designed for solid tumours (neuroblastoma, melanoma, osteosarcoma and small cell lung). Along with the CAR, there is a safety switch, dnSHP2 (blocks PD-1, CTLA-4, TIGIT, 2B4 and BTLA signaling), chimeric cytokine receptor (to further enhance expansion and persistence), and a dnTGFbRII receptor.

Then, next year, AUT07 (all of the same 'modules' as 6NG), which will not only locally secrete IL-12, but also the CAR has been designed to have improved activity in an acidic TME, and is able to target PSMA+ cells that have greatly reduced antigen expression.

The company continues to look at ways to improve antitumour activity, and have in-licensed this https://www.nature.com/articles/nbt.4086 https://link.springer.com/article/10.1007%2Fs00262-021-02853-3

[scotty3371]

https://www.frontiersin.org/articles/10.3389/fimmu.2020.00492/full