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• The Data Monitoring Committee (DMC) is charged with monitoring the safety and efficacy results of clinical trial. The committee and its chairman are totally independent of NWBO.
• The Chairman of the DMC says there has been no interim analysis for efficacy of the phase 3 trial. Feuerstein alleged that efficacy results were negative and that NWBO buried the data to avoid a hit to its stock price.
• The Chairman says that the DMC has not provided any access for the Company to any clinical trial data. Feuerstein claims that the company had seen efficacy data, that it was disappointing and that this caused the Company to radically change the design of the trial.
• The Chairman says “that it is surprising and troubling to see inaccurate claims being made by commentators (Feuerstein) who seem to lack a fundamental understanding of clinical trial monitoring.  I have been on the DMCs for more than 60 clinical trials, and I have never experienced this type of attack.”

Investment Importance

Northwest Biotherapeutics has notified Feuerstein on numerous prior occasions that many of his statements on the phase 3 trial of DCVax-L were factually wrong. In each case, he has responded that the company was lying and fabricating data in order to manipulate the stock price. Feuerstein routinely ridiculed the Company’s explanation and actually stepped up attacks on NWBO.

The Chairman of the DMC has now made it abundantly clear that NWBO is totally blinded to the data and also that no interim efficacy analysis has been performed. These were lynchpin components of Feurstein’s allegation that the DCVax-L trial was doomed to fail. As most of us had previously concluded, he says that Feuerstein” lacks a fundamental understanding of clinical trial monitoring.”

The ongoing attacks on NWBO in Feuerstein in the 18 negative articles he has written over the last five months have had an enormously negative impact on the stock price and the credibility of management. It is now clear that Feuerstein’s allegations had no factual basis and were blatantly wrong. I would hope he would apologize to investors and set the record straight, but I don’t think that will happen. I am curious if he will try to refute the statements of the Chairman of the DMC.

Recent Feuerstein Article

Adam Feuerstein of TheStreet.com published his 18^th negative blog on Northwest Biotherapeutics on August 13, 2014. The report was titled “Northwest Bio DC-Vax Study Changes Hint at Failure”. On prior occasions, NWBO has responded to sensational articles written by Feuerstein in an effort to set the record straight. This rebuttals have had limited effect. This new rebuttal is very different. It includes some very angry comments from the Chairman of The Data Monitoring Committee that is monitoring the trial.

Feuerstein in his article maintained that an interim analysis of the phase 3 DCVax-L trial had been made and that the company “buried the interim efficacy analysis of its DC-Vax brain tumor clinical study in a deep hole, never to be seen again.” This assumes that an efficacy analysis had been done and that NWBO had seen the results. Feuerstein then implies that NWBO changed the trial design because it knew the trial was doomed to fail. Anyone with even a vague understanding of how clinical trials are conducted knows that companies are blinded at all times to the results in a clinical trial. Here are some key quotes from the Feuerstein article. He says:

“I long believed Northwest Biotherapeutics (NWBO_) buried the interim efficacy analysis of its DC-Vax brain tumor clinical study in a deep hole, never to be seen again.”

“It seems obvious that DC-Vax came up futile in the interim efficacy analysis of the phase III study data conducted in December 2013, leaving almost no chance the experimental cancer vaccine would delay tumor progression or prolong survival.”

“Absent any hope of rescuing DC-Vax from failure with the brain tumor study designed as is, Northwest Bio announced a radical -- and seemingly desperate -- re-working of the study.”

“Northwest Bio can argue all it wants to the contrary, but the need to dramatically boost the statistical power of a study years after it begins shows that there is no efficacy signal with DC-Vax at all. Northwest Bio is flailing, but then, anyone who bothered to dig deep into the prior DC-Vax studies knows the cancer vaccine is nothing more than a placebo.”

“With Northwest Bio, logic often takes a back seat to stock promotion. Monday's announcements were no different.”

Northwest Biotherapeutics Management Response

Northwest answered Feuerstein’s allegations as follows. There was no interim analysis on the phase 3 trial and the Company had no access to data at any time. The only analyses to date have been analyses solely about safety (not efficacy), and those safety analyses have been conducted solely by the independent Data Monitoring Committee (DMC), with no involvement of the Company and no communication by the DMC to the Company except to direct that the trial should continue.  The Company has had no access to any information about either safety or efficacy in the trial at any time.

In past occasions when the company made these statements, Feuerstein accused them of lying and would continue his personal vendetta against the Company. It was the Company’s word against Feurstein’s. This time is very different. Dr. Curt Furberg, the Chairman of the Data Monitoring Committee for the phase 3 trial of DCVax-L totally confirmed the statements of NWBO management and called out Feuerstein. He says:

“As the Company has stated clearly and specifically in its public announcements, the DMC has not conducted any efficacy analyses and the DMC has not provided any access for the Company to any clinical trial data. The DMC adheres to established clinical trial monitoring procedures and does not release any data while the trial is ongoing.  This is an important issue, and it is surprising and troubling to see inaccurate claims being made by commentators who seem to lack a fundamental understanding of clinical trial monitoring.  I have been on the DMCs for more than 60 clinical trials, and I have never experienced this type of attack.”

Further Statements by Northwest Management

The Company reiterated that it had no access to any data about the trial at any time, it was impossible for the Company to have been motivated or shaped by any such information or any “hint of failure” about the trial in seeking regulatory approvals for the enhancements of the trial announced on Monday.  Feuerstein’s assertion of such “hint of failure” lacks any basis and is a total fabrication.

The fact that the Company has had no access to any trial information was also a key factor in obtaining approval from the regulatory authorities in the US, UK and Germany for the enhancements to the trial.  Regulatory authorities do not allow changes to be made in an ongoing randomized, blinded trial if the changes are, or might be, based upon any knowledge about clinical data in the trial.

CEO Linda Powers said “The fact that there has been no interim analysis for efficacy and that the Company has had no access to trial data, is very clear and very simple. There is no room for any honest confusion.  Feuerstein’s ongoing false claims about these points are either deliberate falsehoods or reckless disregard of the truth.”

The Company reiterated that its Phase III trial was already solidly designed prior to the enhancements just announced, with a conservative assumption that the extension of Progression Free Survival (PFS) in patients treated with DCVax-L in the Phase III trial would be only 1/3 as long as the extension of PFS (compared to PFS with standard of care) that was seen in patients treated with DCVax-L in the Phase I/II trials.  This conservative assumption in the Phase III trial design was and is also combined with strong statistical powering in the trial design (with an anticipated “p value” of 0.02).

The enhancements of the Phase III trial do not in any way seek to “rescue” a trial that is already strong and solidly designed.  The changes seek to prevent external variables from potentially distorting the results of the trial, while also having the added benefit of further lowering the threshold for the primary endpoint to be met from 6 months’ difference in PFS to 4 months’ difference in PFS between patients treated with DCVax-L and the control arm.  This is a further de-risking of the trial, and as such is a valuable enhancement.

The Company also reaffirmed the encouraging survival data in 55 compassionate use “Information Arm” patients that was released by the Company.  All of the data was collected and maintained by an independent contract research organization (CRO), not the Company.  The Company reported clearly that the data were gathered in a compassionate use “Information Arm” outside the Phase III clinical trial.  The Company simply reported the factual results gathered by the independent CRO.  Even Feuerstein acknowledges that the data are strikingly positive.

Feuerstein’s questions about why those 55 patients were handled separately from the Phase III trial are once again baseless and reflect a lack of understanding of clinical trial design.  As the Company explained in its announcement, it is well established in the medical and research communities that “rapid progressor” GBM brain cancer patients have a significantly different version of the disease than regular GBM patients.  It is fundamental to clinical trial design that the patients included in a trial must be as homogeneous as possible, in order for the data to be as comparable as possible among the patients in the trial.  The Company has followed these fundamental principles in its Phase III trial design.

The Company re-confirmed that the Phase III trial has, in fact, expanded to multiple sites in the UK and Germany as the Company has previously stated.  Feuerstein’s false claim that “none of the European sites have materialized” is directly contradicted by the Phase III trial profile on www.clinicaltrials.gov that he himself cites.  At the bottom of the trial profile there, both the first UK site and the first German site in operation are clearly listed. The listed UK site has been in operation for well over a year.  The listed German site was the first among several German sites to which the trial has expanded.