NorthWest Biotherapeutics Inc (NWBO)

[sentiment_stocks]

So
• we agree that the sampling from the article you referenced is small.

• we agree that we don’t have any criteria to compare that small sample to the DCVax patients other than some of them were methylated and some were not (we don’t even know the numbers on that) and that they all had GBM.

I’m obviously not sure how they intend to build the comparison control arms from the “concurrent and COMPARABLE (capped again for emphasis, lol)” trials - whether it will be matching patient for patient by age, sex, meth status, IDH status, K-scores, etc. - or if they intend to just compare the entire control group of selected trials to the DCVax-L treatment. It’ll be interesting to see how those comparisons are presented. I think it’s premature, however, that you disagree that they will be comparable, seeing as the data has not even been presented yet. Why not set your confirmation bias aside for a spell and see how this all sorts itself out, before you chose to disagree?

I have no idea why LL chose to stop the curve at 36 months. I’m curious. For what reasons do you think she/they did?

As for mentioning filing BLAs, Management indicated in their 2nd quarter 2020 Q that they were expanding their agreements with other KOLs who would play integral parts in helping the company prepare these applications. Apparently, reimbursements appear to be dependent into reaching milestones, so one would think these same KOLs would probably have a vested interest in seeing that the BLAs are filed.

Item 5. Other Information
Consulting Agreements
The Company is in the process of entering into expanded agreements with certain Scientific Advisory Board members and certain other key consultants whom the Company anticipates will play important roles in helping the Company prepare for potential applications for regulatory approvals of the DCVax-L product. The agreements are being negotiated around structures that are contingent upon major milestones and will provide substantial incentive compensation.
https://www.sec.gov/ix?doc=/Archives/edgar/data/1072379/000110465920092797/nwbo-20200630x10q.htm

You may have done a quick search on using external control patients (in the K, I assume), but I did an even longer review on the December 2019 FDA guidance for Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products Guidance for Industry. After looking at it very closely, I would have to disagree with you and suggest that the FDA is signaling their willingness to consider ECTs in certain trial settings.
https://www.fda.gov/media/133660/download

They indicate they are willing to do so for diseases with high and predictable mortality in rare diseases, and GBM thoroughly fits that description.

In fact, despite the limitations, the FDA believes that strong support for effectiveness can emerge when these four criteria are met.
(1) the natural history of a disease is well defined,
(2) the external control population is very similar to that of the treatment group,
(3) concomitant treatments that affect the primary endpoint are not substantially different between the external control population and the trial population, and
(4) the results provide compelling evidence of a change in the established progression of disease.

I think that GBM and the DCVax-L trial meet those four criteria. The FDA also makes the point that approval decisions for any drug also centers around whether the safety of a drug, and whether its risk outweigh its benefits. Since there is little to no risk to be had by taking DCVax-L, that metric should weigh significantly in favor of a DCVax-L approval.

But as for your opinion that there is “no chance in hell” for an RA allowance of the ECTs, it is simply that, your own opinion. I thank you for sharing it with us, and I wouldn’t expect anything less coming from you and exwannabe, so no surprise there.

As for the provenance of the 25% alive at five years, that is likely coming from board extrapolations as to how we think the treatment arm in the trial may perform. So no, that 25% claim is not coming from any actual data.

LL did make this particular point with her audience in her recent presentation in Utah,

And I can tell, as a clinician, when I go to my patients and ask them, would you like to enroll or would you like to get a treatment where there is, say, a hundred percent chance that you will live three to four months more, because that’s the usual survival advantage that we’re seeing in these trials when we look at median survival… so would you like to live a few months more or would you like to have a 25% chance that you will live three to five years? If you put it in that human context, most people would say I would rather take the chance that I will have a durable response and live three to five years as opposed to that hundred percent chance that I’ll live a few months more, but this won’t be a durable response for me.

But I’m sure all of us would agree with you that the treatment arm needs to be compared to a valid control. It’s just that many of us disagree with you as to what is considered a “valid control” as it seems these days, the FDA is willing to consider ETCs valid, is some cases. A randomized control trial is a very valid, if not perfect control when there is no crossover. Unfortunately, when there is a crossover to treatment, it’s not so perfect, or I'd argue valid, anymore.

You’ll be thrilled, though, to know that you’ll still be able to see how the control arm for this trial compares to the treatment arm for the trial, as that is now the fourth secondary objective (I wonder if that’s the same as an “endpoint”?).

I hope you and your family are doing well too. :)