NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

Lykiri, thanks again. That was one of the more important posts in a long time. I'll repost it here with a few comments below.

STUDIES
Manufacture of immunotherapeutic DCVax®-L for brain cancer patients
In recent years, the Fraunhofer IZI has been the manufacturer of a clinical investigational product for test centers in Germany and the United Kingdom, the effectiveness of which is still being reviewed in the context of a phase III clinical trial.

The DCVax®-L immunotherapeutic agent was previously successfully used in smaller clinical trials by US biotechnology company Northwest Biotherapeutics Inc. in the United States. This advanced therapy medicinal product (ATMP) is based on autologous dendritic cells for the treatment of glioblastoma, a particularly aggressive form of brain cancer.

In order to manufacture DCVax®-L individually for each patient, both tumor tissue and a blood product were taken from the patient and then the cell-based therapeutic was produced in a complex, multi-step manufacturing process. The recruitment of the number of patients statistically necessary for the study was completed in 2015, thus successfully completing the manufacturing and testing activities at Fraunhofer IZI.

However, since the therapeutic is administered in multiple doses over a period of 3 years to the patients participating in the study, cryopreserved clinical trials samples were sent in 2017 to the participating clinical trial sites for patient application.

This process will continue in 2018 until the last scheduled dosage is shipped. Thereafter, evaluation of the clinical trial by sponsor Northwest Biotherapeutics Inc. is expected. _Fraunhofer 2017 in review.

1. Unlike Fraunhofer's publications in previous years, I could not find the English 2017 annual report version. Perhaps English, under current circumstances, is less important to Germany in the age of our current citrus haired leader. He probably reminds Germany of the guy who they'd rather forget.

2. Like Dan, I use Google translate, so not all translation is likely accurate.

3. The Fraunhofer 2017 review was probably published in or around April 2018, because Fraunhofer usually comes out later with its annual review publications. Sometimes as late as September.

4.. If you look at the quote above, you will notice great care was taken not to say the German product was DCVax-L, and there was great care taken not to deny the German product was DCVax-L. One can even see that with poor foreign language skills and a generic translator. Many of us here think we know why this might be, but in the end, it is only speculation.

5. A similar but less aptly arrived at misdirection was attempted by UCLA, imo, when they tried to lose the modification scent by confounding DCVax-lung with DCVax-Lysate. One might rethink why that trial has not started yet if you posit there are patent modifications at stake.

6. I seem to recall one other source also carefully not committing to similarity or differences from pre-German manufacturing to post-German manufacturing. Can anyone remind me who that was?

7. Nevertheless, imo, Germany clearly tinkered with the manufacturing process. At one point, they had 90 employees working on the project. Pretty astounding when their enrollment goal was 87.

8. For newbies, there was a very long debate on this board some time ago regarding what happens to trial integrity when manufacturing of a cellular product is changed (more common than you might think) during a trial. There were a few different conclusions. My conclusion was that an adaptable FDA (and other international regulators) are becoming somewhat more flexible, and if the product is safe yet more potent and otherwise basically the same, it would still have an opportunity for approval.

9. The experiment here is this trial started in about 2007 in earnest. Big Pharma were scared a product like DCVax-L would kill people via an autoimmune response. The reason they were wrong is, despite other modifications, DCVax-L still uses the lock and key system that evolution developed in our immune systems to distinguish friend from foe. The antigen is the key, and an as yet undetermined number of varying t-cells present the potential locks. (Car-ts bypass this safety lock and key system). Anyway, I digress. The huge safety gamble regarding DCVax-L paid off. It's basically safer than aspirin. Big pharma could not take that risk, because an entire company could be sunk by taking those types of chances.

10. Enter Germany. Once safety became self evident, it is my opinion that Germany had something to offer by utilizing a more potent version of DCVax. Notice Fraunhofer can't bring themselves to calling their product in the phase III trial "DCVax-L." If you have any understanding regarding the incredible complexity regarding cells, you'd realize that even if Germany could look at all their assays and lab reports telling them their likely optimized manufactured cells were the same as UCLA's cells, save them possibly being more potent, they could still not tell you if they were the same cells. Biology is still that much more advanced above and beyond human understanding.

11. The curveball is the reason given by NWBO for consolidating back to Memphis and Sawston. Was Germany worse at manufacturing, better, or were they simply part of the plan? NWBO had made it seem like only Cognate knew what they were doing. Germany played along with this by saying there were many challenges and so very much paperwork. However, now we learn, a couple years later, this was apparently all part of the plan. Germany reached its necessary statistical enrollment.

12. Germany, as some of us pointed out earlier, also manufactured the U.K.'s doses even before Germany started manufacturing for their own citizen's. Is that still the post WWII reticence of experimenting on one's own people? Nevertheless, they finally did -- after other countries used their citizens to prove safety. How did it turn out? That is what we are supposed to find out in either or both the trial results and/or the blinded publication.

13. Someone here once offered the question if Germany's assistance will go a step toward squaring this atrocities during WWII. Of course not. Nor will it help the Norwegians with their raping and pillaging days, nor the Serbs' recent atrocities, nor the WASPs when they wiped out 90% of native Americans, nor the Hutus, nor so many other nationalities that went temporarily insane. However, they will help humanity now if their efforts optimized DCVax, and if DCVax is advanced enough to knock a serious blow to cancer.

14. I pray the results will demonstrate humanity has taken a step forward.


This has all been my opinion.