Replies to post #422023 on NorthWest Biotherapeutics Inc (NWBO)

[biosectinvestor]

Think of it this way, further:

Safety issues cause full halts.

This was a “partial-halt” without clarity as to what exactly that meant, we can only see the result at the end, fewer placebo patients.

If it was a safety issue having to do with giving DCVax, then why were all the patients receiving DCVax still getting it and still starting to get it? Those would be the partial patients you’d halt, except when you halt giving the drug to your, you don’t continue adding patients whenever they “enrolled”, placebo or otherwise.

Furthermore, with a safety issue, doctors, patients, everyone needs to be notified and the doctors are not “on the side of the company”, they are doing their duties as doctors, so they are not going to hide what that was about in a journal article. It would be fully disclosed. It was not there. All of those doctors and institutions they work for would be involved in a major fraud? That would be completely bananas and factually unlikely.

And as I said, it would have necessarily been disclosed in the lawsuit, and that motion to dismiss would likely not have been granted and if even despite that granted, the judge would have had such material facts in the opinion.

I do not think people understand the limits of discretion and confidentiality here or that they’d not want to be in a company that kept such major facts secret. Which I do not believe they did, I think they said what they knew or they’d be in trouble, and LP and LG know that clearly, quite well.

Yes, the PFS was the wrong measure, most likely because of pseudoprogression. Crossover caused issues too, and then the almost arbitrary result of the conflict of laws here, led to the reduction of the placebo arm.

No one is going to convince me that the regulators will not do what they can to make this a valid trial for any number of ethical and legal and constitutional reasons. And further, assuming the results on survival are at least as good as the interim article compared to what is commonly said and understood to be the case with GBM patients under the current standard of care, it isn’t personal conclusion and belief that it will be very difficult for the regulators not to approve based on those results, but the primary issue that has concerned regulators over the years has been replication of a quality cellular product, which appears not to be an issue here generally, and is similar to those for Car-T, and manufacturing at scale, which would make regulators much more enthusiastic.

I think the company is well on their way to resolving those issues satisfactorily as well.

I don’t agree that Flaskworks merger was set in stone when likely the various people may have been in touch, though I do think it was always thought if Flaskworks worked, NWBO would be a major customer. But events worked out so that the fate of the companies was inextricably intertwined and there were not enough customers yet, that it made the most sense that NWBO simply buy the company and work to advance the technology even faster, which I have said many times I think will be the result and the end will not be discrete machines but a much larger process in a factory that uses the space most efficiently to manage the manufacturing. Initially they will go the simplest route, to get certified for Flaskworks, but eventually, this company’s manufacturing, just from what I know about recruiting manufacturing engineers many years ago, will be much more complex and higher tech even than that if DCVax is a success, which I expect to be the case.

[Dan88]

Appreciated very much for your well-thought out replies biosectinvestor. I understand where you are coming from. Yours is obvious a possible reason, though I think it may be somewhat a stretch.

There are different perceptions and perspectives on the same issue of pseudo progression from different parties. At the time of the partial halt, pseudo progression was already a known phenomenon for NWBio, clinicians running the trial, and regulatory agencies. The problem is when it happened to a patient there seemed to having no ways to distinguish either right on the spot or very shortly the event was in effect due to pseudo progression. So for the regulatory agencies, they had to assume it was a disease progression upon it was approved otherwise; for NWBio it could argue such events were most likely and mostly pseudo progressions, suggested by the underlining patients as a whole have instead lived longer than the rest of the patients in aggregate. So despite seemingly quick disease progressions (one characteristic for pseudo progression events) , these patients have also lived longer than those patients who have experienced disease progressions later (after the exclusion of rapid progression patients from the trial during the 3-month screening process, a characteristic for true disease progression events) which obviously contradicted to the known fact that disease progression normally correlates to underlining overall survival, i.e., the more delayed in disease progression, the longer the overall survival of underlining patients.

In light of the above, I don't think FDA when it initiated the partial halt would consider the halt a straight-forward safety halt. It might just want to give the company time to fix the problem or later provide it with more persuasive and convincing data that would indicate most such suspected events were indeed not harmful to the patients who have experienced the events. Since the halt was lifted by FDA, I do think NWBio was later able to provide to the FDA such data which not only has it showed the underlining patients have lived longer, but they also have experienced better quality of life.

It is in this sense and circumstance I also don't think the partial halt had anything to do with safety at the time. Today it can be said with almost certainty that both NWBio and FDA are on the same page regarding pseudo progressions, i.e., the more than expected disease progression events experienced in the trial are indeed mostly due to pseudo progressions; and it is also suggested NWBio may have found ways to distinguish between pseudo progressions and true progressions, evidenced by the listed second secondary endpoint in the now revised SAP, i.e., cPFS.

All in all, pseudo progression may be a strong indication that DCVax-L is not only safe by also very efficacious. It causes no harm to patients; instead it is a blessing.

GL and best wishes !

[There are not posts left for me today. Thank all]