NorthWest Biotherapeutics Inc (NWBO)

[Leprecon7777]

IMHO...
Given the body of evidence to date, I believe, as others do, it is more likely than not that the IA resulted in NWBO applying for AA, and the reason for withholding information is to protect the integrity of the trial while OS is used as confirmation.

NWBO has not exactly been entirely silent.. I believe NWBO has left bread crumbs for us to follow. Listed below are numerous links and excerpts, and in some of these NWBO has given circumstantial evidence to indicate the clinical trial is going well. I highly doubt, NWBO would highlight this evidence if the IA has resulted in a futility recommendation. To do so would certainly provide lawyers with mounds of ammunition to file lawsuits.

Of particular interest is the Sep 1, 2017 PR in which NWBO high-lighted the "projections by independent analysts" for OS and PFS survival. I believe NWBO would be placing itself in legal jeopardy for mentioning this if the IA had resulted in a futility recommendation.

And lastly, I believe NWBO released the enrollment curve knowing full well that this information could be used to model the trial. Multiple models (JimmyJames, AlphaPuppy, Branko, and others) have all suggested the clinical trial has a good chance in resulting in success. This was not just a bread crumb, but more like a slice of bread. Of course, nothing is guaranteed.

If the partial clinical hold was for safety, NWBO would be obligated to divulge this information (especially since the clinical hold was been lifted). If the partial clinical hold was due to futility, NWBO could continue the trial but I believe the company could not legally (directly or indirectly) tout the efficacy of DCVax-L. To do so would be highly misleading to investors.

Bread crumbs to follow:

2015 Aug 21
https://www.nwbio.com/nw-bio-confirms-phase-iii-trial-of-dcvax-l-for-gbm-brain-cancer-is-ongoing/

The only change in status of the trial is that new screening of patient candidates for the trial has been temporarily suspended while the Company submits certain information from the trial for regulatory review

2015 Sep 14
https://woodfordfunds.com/words/insights/wpct-august-2015/

The portfolio’s US biotech holdings were hit particularly hard. The month’s largest detractor was Northwest Biotherapeutics, after rumours that the clinical trial of its DCVax-L oncology treatment had been suspended. The company has confirmed that the suspension related simply to the recruitment of new patients and was a temporary measure while regulatory information was submitted, in line with clinical protocols. The trial is continuing and we see nothing untoward in this development. Alkermes and Prothena sold off heavily too – again, we have no fundamental grounds for concern.

2015 Oct 19
https://www.nwbio.com/nw-bio-issues-statement-on-highly-unusual-trading-activity/

"NW Bio is not aware of any fundamental reason for the substantial decline in the price of the Company’s stock on Friday, October 16. Indeed, NW Bio presented encouraging clinical data at scientific conferences in London and New York as recently as mid-September."

In the DCVax-L Information Arm, for the 25 GBM patients with apparent early tumor recurrence at one of two time points, 40% of the patients have now reached or exceeded approximately 3 years’ survival. This substantially exceeds the expected survival time of about 15 months even for regular GBM patients without early tumor recurrence.

2015 Aug 25
https://www.sec.gov/Archives/edgar/data/1072379/000114420415051646/v418946_ex99-2.htm

The supposed “confusion” about our enrollment is, once again, certain bloggers and commentators trying to turn good news into bad news about NW Bio and its trial. People familiar with clinical trials are generally aware that screening of patient candidates for eligibility is different than recruitment or enrollment of patients for treatment.

2015 Oct 21
https://www.nwbio.com/nw-bio-has-entered-into-an-agreement-for-30-million-of-new-equity-funding-from-woodford-investment-management/

NW Bio has reported encouraging interim clinical data from both its DCVax-L and DCVax-Direct clinical programs, both last spring and recently, with patient survival exceeding expectations. With this new funding from Woodford we look forward to moving these clinical programs ahead vigorously while continuing to build our organization” commented Linda Powers, CEO of NW Bio.

2016 Jan 8
https://www.nwbio.com/nw-bio-issues-statement-on-adverse-market-conditions-and-nw-bio-stock-decline/

In the DCVax-L Information Arm, for the 25 GBM patients with apparent early tumor recurrence at one of two time points, 40% of the patients had reached or exceeded approximately 3 years’ survival. This substantially exceeded the expected survival time of about 15 months even for regular GBM patients without early tumor recurrence.

2016 Dec 8
https://www.nwbio.com/nw-bio-provides-update-about-phase-3-trial-of-dcvax-l-for-newly-diagnosed-glioblastoma-multiforme-brain-cancer/

Since the summer of last year, the trial has been subject to a partial clinical hold, only on recruitment. As a result of the partial hold, the Trial has not enrolled the last 17 of the total 348 patients. To date, the regulators have not agreed to remove the partial hold, but have allowed all of the patients in the Trial to continue being treated in accordance with the Protocol. The Company is pursuing ongoing dialog with regulators. However, at this point the Company believes that the potential benefits that could be obtained from enrolling the final 17 patients would not be worth the time it would take, as the process of re-starting and re-training the sites (including through Institutional Review Board renewals) for further enrollment would take months, followed by further months for the recruitment itself.

2017 Feb 6
https://www.nwbio.com/nw-bio-announces-lifting-clinical-hold-dcvax-l-phase-iii-trial-fda-progression-free-survival-events-reached-overall-survival-events-not-yet-reached/

On February 3, the FDA lifted the partial clinical hold which had been in place on the Trial. As previously reported, the Company has been in an ongoing dialog with regulators. The dialog culminated in the FDA lifting the partial hold. As previously announced by the Company, and as the Company also informed the FDA, the Company has closed enrollment and is not going to enroll the last 17 of the planned 348 patients.

Dr. Linda Liau, Principal Investigator of the DCVax®-L Trial commented: “It is gratifying to have the hold removed from the Trial and exciting to see this Trial now moving towards completion, although of course the longer it takes for PFS and OS events to accrue, the better the patients in the Trial are doing.”

2017 Sep 1
https://www.nwbio.com/dcvax-clinical-program-updates-presented-dr-marnix-bosch-boston-scientific-conference/

Dr. Bosch’s presentation reflected the breadth and consistency of NW Bio’s DCVax platform and clinical programs, which include the following:

50 patient Information Arm of the DCVax-L trial, which included multi-year survival and a long tail,
40 patient Phase I/II Trials of DCVax-L, which included multi-year survival and long tails,
41 patient DCVax-Direct Phase I trial for 13 different solid tumor cancers, which included multi-year survival and long tails
331 patient Phase III GBM Trial, which it appears, based the trial metrics reported in the Company’s industry presentation during ASCO, may include multi-year survival and a long tail;
preclinical studies of DCVax-L combined with checkpoint inhibitor by collaborators, which included substantially expanded response rates.

In reviewing the Phase III GBM Trial, Dr. Bosch’s presentation also took note of encouraging projections by independent analysts in regard to the median overall survival (OS) and median progression free survival (PFS) based on the trial metrics reported by the Company during ASCO.

Additionally, Dr. Bosch provided an update about the Company’s multiple draft publications in process about the Phase III Trial of DCVax-L and the Phase I DCVax-Direct Trial. The DCVax-L publication has been drafted over the course of the summer with input from a number of investigators, and is currently being finalized.