NorthWest Biotherapeutics Inc (NWBO)

[VuBru]

There is a lot of crazy talk these days about NWBO. Ongoing lack of information updates leaves an ambiguous situation that is easy to interpret from ones own biases and fears. I was hoping to post a few bits of reality, if for no other reason than to make myself feel better about the situation. Here's what we have:

1) Statements in yesterday's filing about COVID delays appear to be interpreted by some as indicating that there is an ongoing delay, resulting in the company (and advisory board) still being blinded 6 months after data lock. I can conceive of no set of circumstances where that is remotely plausible, even if they did have to "validate" certain data more after data lock. The latter situation also goes against the whole rationale for having a data lock -- it is the final dataset for analysis and cannot be changed further. They announced data lock 6 months ago. Ergo, the statisticians have been analyzing and the company and SAB have seen the data at some point since data lock. Analyses do NOT take anywhere close to 6 months no matter how detailed they are. That is impossible.

2) If the trial had totally failed (original endpoints and comparisons versus historical controls), there would be no reason to drag this out for 6 months "pending publication and release of TLD" as their PRs have indicated. Blinded data presented previously support DCVAX as being effective compared to historical controls. So, they are publishing a TLD article that at worst shows significant benefits compared to historical controls, and at best shows the original endpoints succeeded. The fact that they are clearly delaying TLD for release with a simultaneous publication (the only theory that makes sense), we can infer that the data probably do not show the original endpoints succeeded but all evidence suggests that historical comparisons will succeed. They want to provide appropriate context for the TLD to avoid misinterpretation.

3) Some question whether the key endpoints have really been changed to historical comparisons, citing lack of announced "FDA approval" of that change and failure to update clinicaltrials.gov with the new endpoints. The following are relevant: a) the endpoints HAVE been officially changed by the agencies responsible for posting these changes outside the US, without a shred of doubt. b) The FDA never formally "approves" ((on the record) protocol changes unless done as part of a special protocol assessment (not relevant to NWBO). They will either say informally "that looks perfect" or (more likely) say "that change will raise several issues and we cannot guarantee how the review committee will respond." c) If there is no formal FDA approval of changes, why would the company update CT.gov (which is their their responsibility, unlike Europe). CT.gov is relevant to publication in top tier journals, but has nothing to do with the FDA approval process. I am not even sure administratively whether it is possible to change the primary endpoints on CT.gov after a study has ended (defeats the whole transparency purpose of the website). All changes have to go through a series of reviews - the company cannot just make them.

4) An interview with LL recently posted made clear that she feels historical controls are necessary and justified in trials like this, and also highlighted the importance of GBM treatment focusing on mechanistically relevant subtypes (no one size fits all treatment). We can infer from this that TLD analyses might show success only in particular GBM subgroups (e.g., methylated). Clearly she is totally on board with the revised SAP though. The fact that her UAB presentation included a slide with pooled historical control OS values across the most relevant studies makes pretty clear that they are using this approach in the new SAP (and were far enough along in analyses to have the comparison data available for that slide).

5) Many complain about lack of a stated timeline for TLD, and blame this on poor communication by the company. They may indeed be historically bad at this, but the company in this current situation cannot give a timeline because they are at the mercy of the journal that will publish the results. They really do not know. It is possible they may have to send it to 2-3 journals to get it published, and each journal starts a new clock on the process. This article will definitely get published, but it is not an easy sell despite the potential clinical importance. This is no longer a randomized control trial (it is not being analyzed that way). It is a case-comparison study, which in truth is a fairly mediocre research methodology, even if it is fully justified given the circumstances (changes over time in state of the art, confounding due to crossover, pseudoprogression). The company and the SAB have elected to use a less compelling analysis because they believe it is important to get the findings out there (indicating that they are assuming success) and find a way to show DCVAX works in spite of all the methodology limitations. This type of study is unlikley to get accepted by top tier journals, but if I were them, I would at least try this route first even if unlikely to be successful. As a result, the publication process has been extended, and the company cannot tell us how long it will take. It will be over when it's over.

6) Somebody posted that a psychic told them the trial results would be good, but not announced until around May. I thought that long a process was ridiculous at the time, but maybe that psychic was on to something.

Personally, my wife and I have 180,000 shares long and we are holding based on the information above regardless of what the AFs of the world say.