NorthWest Biotherapeutics Inc (NWBO)

[norisknorewards]

to mlevine51 @bloomberg

Hi Matt,

I am reaching out with a potential interesting story regarding a Phase 3 clinical trial. The company is called Northwest Biotherapeutics. I hope you will read this and perhaps do a bit of digging and see if your media presence can help to bring attention to this company and their life saving glioblastoma treatment. The company was valued approx. @ $2billion prior to release of highly encouraging results, but after release the stock was hammered down to under $500m at one point during intraday trading, settling today around +-$750m.

The company has been under a regular short trading attack conducted by a psudo-journalist Adam Feuerstein, a notorious blogger who regular works to crush small promising biotechs. It sadly appears his efforts by himself and those short hedge funds behind him have accomplished another attack throughout the day yesterday crashing the price down over 70%

Presentation is here from the NY Academy of Sciences that took place yesterday. Trial results were excellent, achieving their 2 primary endpoints.. https://virtualtrials.org/dcvax/dcvax.pdf

Northwest Biotherapeutics is a very controversial company, and has been for over a decade. They have just released long awaited top line data for their lead trial in glioblastoma multiforme (GBM), the most lethal primary brain cancer with typical 5-year survival rates around 5%. There have not been significant advancements in GBM treatment in at least 15 years with a protocol that increased median survival (mOS) to around 15 months (a number replicated in numerous studies since).

In NWBO’s Phase 3 study of DCVax-L, newly diagnosed patients achieved mOS of 19.3 months vs 16.5 in control arms. What is more interesting, though, is the ‘long tail’ of survival that was achieved. For example, 13% were alive at 5 years vs only 5.7% in controls. Additional subset detail is available in their slide presentation.

There are two primary points of controversy with this trial, both related to them changing trial endpoints after the trial began (but, importantly, before the trial data was unblinded):
1. The study began with a primary endpoint of Progression Free Survival (PFS). This was originally due to the company including a crossover arm (for ethical reasons) where patients receiving the placebo could then receive the drug after they progressed. Unfortunately, this makes measuring overall survival between the trial and placebo arms impossible. In the case of this trial, 90% of patients ultimately received DCVax-L. What is interesting is negative bloggers have been stating for years that the FDA would never accept a trial with a primary endpoint of PFS. Now those same bloggers are ignoring the OS benefit altogether and making a (false) claim that the trial failed on PFS.
2. The new primary endpoint is OS against an external control arm. As mentioned, measuring against a placebo would not be viable given the crossover arm, especially since such a high percentage of patients took advantage of the crossover option. There is an argument against the company that regulators will not accept external controls. Regulators outside of the US approved changes to clinical trials, and both UK and EU have accepted the new endpoints. While it is true the FDA has not stated a position one way or the other, any BLA submitted will use the same analysis. It is reasonable to believe the FDA will approve given the risk/benefit of the drug vs mortality rate of GBM. Since external controls are a very new topic in medicine, it is inappropriate to only consider one side of the argument, and further, to make any allegation/insinuation that control patients were cherry picked, as there is no data to support this.

Any questions please advise.