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Expert Financial Analysis and Reporting

Northwest Biotherapeutics: Adam Feuerstein Investigates Adam Feuerstein’s Understanding of Dendritic Cell Vaccines

Key Conclusion

Let me ask you a question? If F-stein is trying to convince you that DCVax-L has no chance of being effective in glioblastoma multiforme (GBM), wouldn’t you expect him to have a good understanding of the biological basis for the product, its mechanism of action and how it is manufactured (especially the case for a living cell product)? Of course you would. Failing this, everything else he says is meaningless or highly questionable. This report unequivocally establishes that Adam Feuerstein has no such understanding.

In searching through the plethora of articles he has written on Northwest Biotherapeutics, I was unable to find anything remotely resembling in-depth analysis of dendritic cell vaccines. So to get some insight into F-stein’s thinking (sic), I had to turns to bits and pieces of comments he made on Twitter, Investors Hub, Seeking Alpha and TheStreet.com. As you will see, his comments are uniformly superficial and ignorant.

Essentially, I have used Adam Feuerstein to investigate Adam Feuerstein. With his help I conclude, and I am confident that you will agree, that Adam Feuerstein is riding a jackass through the streets of biotechnology with no clothes muttering inanities about Northwest and the sophisticated technology underlying DCVax-L.

Introduction

This is the first in a series of articles that will focus on Adam Feuerstein’s (AF) near decade long, malevolent obsession with Northwest Biotherapeutics, its CEO Linda Powers and its lead product DCVax-L. My goal is to impeach (actually destroy) F-stein’s credibility using his own words. Here is a sample of some of the ugly and factually incorrect comments he has made:

 

May 26, 2017 AF Tweet    NWBO is a corporate malignancy disguised as an enterprise.

 

December 23, 2015  AF Comment on Investors Hub        Linda Powers is happy because much of the money raised today will flow through Cognate and into her bank account. Merry Christmas, Linda!

(SmithOnStocks Comment: F-stein invented the fiction that Ms. Powers was siphoning money out of Northwest through Cognate. A law firm launched a class action suit against NWBO and cited F-stein’s Cognate allegation as the reason. The suit was dismissed. This charge was also the basis of an SEC investigation which concluded that F-stein’s allegation was baseless. It was a total fabrication. In actuality, the money going to Cognate was to produce product for the DCVax-L phase 3 trial.)

 

June 24, 2016 AF Comment on Investors Hub      There is ample justification for a real, external investigation into NWBO's business practices, particularly the constant and exorbitant flow of money from shareholders, through NWBO and to Cognate. That investigation should target Linda Powers.

 

November 18, 2016  AF Comment on Investors Hub        The wheels move slow at the SEC, but eventually, the enforcement branch will nab Linda Powers. Unfortunately, SEC corrective action won't take place until after NWBO goes belly up and everyone holding the stock loses all their money.

 

February 10, 2016 AF Tweet  Linda Liau is an idiot. They need patients to die in order to progress with the study? $NWBO #FAIL http://www.thestreet.com/story/13452761/1/northwest-bio-blames-short-sellers-not-warning-from-expert-doctor-for-stock-plunge.html

(SmithOnStocks comment: Dr. Liau is a neuro oncologist with incredible credentials, co-inventor of DCVax-L and the lead US investigator for the DCVax-L phase 3 trial. F-stein draws on his political science undergraduate degree to school her on the phase 3 trial)

 

February 9, 2016 AF Comment on Investors Hub  My latest story on NWBO focuses on Dr. Liau's Oct. 15 lecture. Her warning about problems with the DCVax-L phase III study was very unusual and important.

(SmithOnStocks comment: Linda Liau has been consistently optimistic that DCVax-L extends survival for GBM patients. F-stein can twist facts faster than a tornado spins)

 

February 19, 2016    AF Comment on Investors Hub  The FDA did not require a crossover in the DCVax-L study. I know, Liau claims otherwise. She's mistaken.

 

(SmithOnStocks comment:  F-stein has been alleged to have frequently tried to contact Dr. Liau numerous times over the years to discuss DCVax-L . There is currently a Twitter firestorm in which some bloggers are tweeting that F-stein intimidated Linda Liau so that she backed out of the New York Academy of Sciences presentation. If so, this is grave misconduct on his part. I have seen no evidence that this happened, but F-stein has not denied it either.)

 

August 12, 2014   AF article on TheStreet.com   “Northwest Bio DC-Vax Study Changes Hint at Failure”      It's obvious DC-Vax came up futile in the early look at the phase III study data, leaving almost no chance the experimental cancer vaccine would benefit patients. 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.

(SmithOnStocks: The phase 3 study was unblinded on October 5, 2020. Until then, there was no way to determine if the trial had succeeded. The only meaningful information until then was an analysis of blinded data from the trial which was very encouraging.)

 

October 9, 2014 AF comment on Seeking Alpha article  “Northwest Bio's Latest Financing Abuses Its Shareholders: Is The Charade Over?”.

I remain very confident that DC-Vax-L will fail. DC-VAX Direct is even more ridiculous. The company will be bankrupt and delisted before Direct reaches a pivotal clinical trial.

 

How Adam Feuerstein Operates

Trying to explain Adam Feuerstein to people is perplexing. He is not an analyst writing carefully written, well documented research pieces. Any references he makes to underlying technology, performance of clinical trials and other issues is less than perfunctory. He counts on bluster rather than reasoned observations. This is not surprising as his undergraduate degree was in political science. There is no Wall Street firm that would think of hiring him as even a junior analyst in biotechnology.

He is also not a reporter who looks at a situation, defines the issues, has in-depth conversations with knowledgeable people advocating for and against, and then goes on to lay out the facts in a balanced article. With him there is no right or wrong, there is only F-stein. He arrives at a point of view and then creates his own fiction to support that opinion. Only in  the rarest of cases, does he acknowledge his sources. So he is not a reporter as most people would define the function.

What we see with F-stein is someone with reckless disregard for facts, who launches vitriolic attacks on companies and their management using vulgar language. He is the shock jock of biotechnology. The best way of coming to grips with F-stein is to look at what he has published over the years. When you do so, I think you will find him as despicable as I do. Over the period of 2013 to 2018, I traced what F-stein was saying on four social media platforms-Twitter, Seeking Alpha, TheStreet.com and IHub. He left TheStreet.com in 2017 to go to Stat News. At that point, I stopped tracking him in part because I did not want to subscribe to Stat News. I collected over 500 comments he made on these forums. I select as appropriate those which give an insight into F-stein’s thinking (sic).

Over the last decade, F-stein has been obsessed with Northwest Biotherapeutics and as the previous comments show, he has displayed unbelievable malice, made accusations of criminality that are patently absurd and dismissed DCVax-L and the technology underlying it. He has created a living hell for management that has sadly drawn too much of their attention from running the company. Presumably, F-stein’s beat is all of biotechnology and one has to question his intensive, relentless focus on tiny, little Northwest Biotherapeutics. His stated goal has been to drive NWBO into bankruptcy and have criminal charges brought against CEO Linda Powers. Of course, with that, the development of DCVax-L would have ended.

We have recently seen the first look at data from the phase 3 trial of DCVax-L in glioblastoma multiforme. Leading neuro-oncologists have called the results a major therapeutic advance based on solid evidence of increased survival for GBM patients. We should all be celebrating this, but F-stein continues his attack and maintains that the phase 3 trial failed. With this. he has broadened his attack from focusing on NWBO to challenging the many neuro-oncologists who are excited about the results. I discuss this at length in two recent articles: Adam Feuerstein Is Facing a Firestorm of Criticism for His Misrepresentation of Results in the Phase 3 Study of DCVax-L in Glioblastoma Multiforme; A Practicing GBM Physician Chastises Him  and Debunking Silly, Fictitious Adam Feuerstein Article Falsely Claiming Phase 3 Trial of DCVax-L in Glioblastoma Multiforme Was a Failure 

In this report, I will show through F-stein’s own words that he has no understanding of the Company’s dendritic call cancer vaccine technology. Lacking this necessary foundation invalidates his conclusions on almost all aspects of the Company. In the next section I give a layman’s view of DCVax-L to be used as a gage against which to measure F-stein’s shocking lack of understanding of dendritic cell cancer vaccine technology. As a disclaimer, I have only a layman’s understanding of what NWBO is doing, but enough to have a 30,000 foot view. However, this contrasts with F-stein observing from the dark side of the moon.

The Technology Underlying DCVax-L

So Just What is a Dendritic Cell?

Dendritic cells differentiate from monocytes, a phagocytic (cell eating) type of white blood cell. Monocytes leave the bone marrow and circulate through the blood. Depending on chemokine signals, they further differentiate into macrophages and immature dendritic cells. Both of these cell types also phagocytose (engulf and then digest) foreign substances such as cellular debris, infectious microbes and abnormal, damaged cells like cancer (which is what we are interested in). Both play a role in activating the adaptive immune system, but dendritic cells are more specialized and play a much more important role. They are referred to as the professional antigen presenting cell and are considered the starting engine of any immune response.

Immature dendritic cells circulate through the blood to take up residence in tissue at potential sites where they may encounter cancer cells displaying antigens. They are present in the blood, tissues in the inner lining of the nose, lungs, stomach and intestines. These immature dendritic cells are geared for antigen capture after which they migrate through tissues following a chemokine gradient into the lymphatic system and ultimately into lymph nodes where they develop into mature dendritic cells.

Cancer cells are mutations of healthy human cells which carry abnormal molecules on their surface that do not occur or occur infrequently on normal cells. These are called antigens and when recognized as foreign, can trigger an immune response that seeks to destroy them. Cancer cells are ingested by immature dendritic cells which process digested antigen fragments and present them on their surface though MHC peptide complexes to other cells of the immune system. A killer T cell can become sensitized to an antigen by first encountering it on the MHC class I molecules on the surface of the dendritic cell. This recognition of the antigen present on the MHC class I peptide complex is generally not enough to activate killer T cells and turn them into cancer cell killers. They need the support of helper T cells. Helper T cells recognize a different collection of peptides displayed as MHC class II molecules. When helper T cells come in contact with these MHC class II molecules containing antigens, they become activated and secrete cytokines that promote the expansion and maturation of killer T cells targeted at a specific antigen(s) on a cancer cell’s surface and B cells that produce antigen specific antibodies.

DCVax-L is Based on Living Cells Which Means that the Manufacturing Process is the Product

In the case of cancer, this natural immune response has not been sufficient to contain or eliminate the cancer. The goal of dendritic cell cancer vaccines is to emulate and bolster the adaptive immune response in the hope that this will allow the immune system to regain its efficacy. In effect, drug developers are trying to replicate the biology that in nature stems from the immature dendritic cell capturing antigens, migrating to the lymph nodes and differentiating into a mature dendritic cell that displays that antigen to T cells passing in the lymph. In nature, this is an incredibly complex process and perhaps even more so in the production of cancer vaccines.

With living cell therapies like dendritic cell-based cancer vaccines, the manufacturing process largely determines the ultimate characteristics of the product. The processes used to grow the cells and alter them can lead to end products which may have the same general approach and therapeutic goal, but whose efficacy can be quite different. The manufacturing starts with leukapheresis in which a tube extracts blood from one arm and runs it through a machine that separates out white blood cells and then returns the blood, which now contains primarily red blood cells and plasma, through a tube in the other arm. Over a period of a few hours, the machine can extract a considerable number of white blood cells which are then shipped to the manufacturer.

The leukapheresis product contains monocytes, lymphocytes, granulocytes and other white blood cells. The manufacturer must then separate the monocytes and culture them to obtain immature dendritic cells. The cells are spun in a process that separates the different cellular components into gradient layers based on their density; one of these layers contains the concentrated lymphocytes and monocytes. NWBO places the cells containing monocytes on a plastic dish to which the monocytes selectively adhere. They then wash away the other cells. The remaining cells are mostly monocytes. The mixture containing monocytes is given nutrients to keep them alive and cytokines that stimulate their differentiation into immature dendritic cells. Mechanical factors such as rocking the culture are also used.

The next important step is to expose immature dendritic cells to induce them to capture antigens that characterize a patient’s tumor. Northwest Biotherapeutics DCVax-L uses a tumor lysate to obtain antigens for its vaccine. When the surgeon removes the tumor, a small piece is sent to the pathology laboratory for analysis. The remaining tumor is washed with saline and placed in a premixed tube containing enzymes. It is then ground up into small pieces, placed in a container and shipped to NWBO by courier.

At some point in the manufacturing process (the timing is a manufacturing art), the immature dendritic cells are exposed to lysed tumor tissue. They ingest the tissue mirroring the natural process in the body. The resultant cells are frozen at cryogenic temperatures to be later injected back into the body at various points in time.; there is considerable art in this freezing process. They can be kept for three years of more so that this results in the production of numerous doses of DCVax-L that can be given at multiple time points. At the time of treatment, these cells are thawed and returned to the patient. As with the natural process, these cells circulate through the lymph system to lymph nodes where they become mature dendritic cells which trigger as immune response as just described.  Like dendritic cells produced naturally, they stimulate an adaptive immune response.

More Precise and Broader Targeting of Neoantigens is the Key Aspect of DCVax-L

This therapy is patient specific in that dendritic cells are derived from the patient’s monocytes and the tumor antigens specific to that patient’s tumor. Proponents of this approach point out that no two cancers are the same. New proteins called neoantigens form on cancer cells when certain mutations occur in tumor DNA. Recognizing and targeting neoantigens plays a central role in helping the body launch an immune response against cancer cells. The number and type of antigens may change over time. This could mean that if a particular drug is developed specifically to target a prespecified antigen may not be effective if mutations have occurred. Over time the antigens  specific to the tumor in its initial phase may not be present later. The excitement of the DCVax-L approach is that is based on antigens that are present at time of surgery.

A Distinguished Physician Views DCVax-L Very Favorably

Dr. Keyoumers Ashkan is one of two neuro-oncologists heading the phase 3 clinical trial of DCVax-L in the treatment of glioblastoma multiforme (GBM). He is the clinical lead for neuro-oncology at King's College Hospital in London. He has an active research interest in brain tumors and movement disorders and heads the Neuroscience Clinical Trial Unit.  Dr. Ashkan is one of the most respected neurosurgeons in the UK and Kings College is the premier teaching hospital in the UK.

Dr. Ashkan describes mechanism of action of DCVax-L as extremely clever. He strongly  believes that immunotherapy is the way forward in the treatment of GBM. He has stated that DCVax-L personalized immune therapy, promises to be an important advance in the treatment of brain tumors. He says that there is nothing more clever than the ability of the immune system to cope with variation and this is what DCVax-L can do. He goes on to say that brain tumors are notoriously hard to treat because they are extremely heterogeneous. Because of rapid mutations that characterize GBM, no tumor in one individual is the same as a tumor in another person. Indeed, the mutations in one part of a tumor in the same person may make it a different type of cancer from another part. He is very hopeful on DCVax-L because it picks up the several neoantigens specific to each patient’s tumor. It them primes the immune system to attack the cancer cells characterized by these different mutations.

Northwest Has a Second Product in DCVax-Direct

Northwest is also developing a second cancer vaccine product called DCVax-Direct. There are many similarities in manufacturing but one major difference is in how DCVax Direct obtains cancer neoantigens. DCVax-L as previously explained is made by exposing immature dendritic cells ex vivo to tumor lysate from the patient. In the case of DCVax-Direct, immature dendritic cells are injected directly into a tumor mass based on the premise that they will capture cancer antigens in vivo specific to the tumor. The promise of DCVax-L has been established with the phase 3 GBM data. Early phase 1/2 results in a variety of solid tumors have produced promising results, but there is much to learn about DCVax Direct.

Adam Feuerstein on Dendritic Cell Vaccine Technology

In the previous section, I have given you a layman’s overview of DCVax-L. I make no pretense of having a scientific understanding. However, my intention is to give you enough of an insight to see how clueless F-stein is. Let me ask you a question? If F-stein is trying to convince you that DCVax-L has no chance of being effective in GBM, wouldn’t you expect him to have a good understanding of the biological basis for the product, its mechanism of action and how it is manufactured (especially in the case of a living cell product)? Of course you would. So let’s go through some of F-stein’s comments and see if you agree with me that he doesn’t have a clue. It is also important to understand F-stein almost never cites an external source. He blurts out an opinion and that is it.

In searching through the “hundreds of thousands ” of word written by F-stein, I was unable to find any writings that addressed the issues I laid out in the previous section. So to get some insight into F-stein’s thinking (sic), I had to turns to bits and pieces of comments found on Twitter, Investors Hub, Seeking Alpha and TheStreet.com. As you can see, the comments are all superficial as is their author.

 

September 7, 2013  AF Comment on Seeking Alpha article entitled Agenus: Assessing Stock Prospects After MAGE A-3 Cancer Vaccine Misses Primary Endpoint In Melanoma by Smith On Stocks

IMUC NWBO GALE are dead stocks walking because their respective cancer vaccines are too weak. Smith and others who perpetuate the myth of cancer vaccines are wrong today and will be wrong tomorrow.

(SmithOnStocks Comment: This is the one of the first comments by F-stein about cancer vaccines as a therapeutic modality that I recorded. His statement reflects the then prevailing investor and medical conventional wisdom about cancer vaccines. There had been blowup after blowup with companies trying to develop cancer vaccine products and as a result skepticism reigned. However, time changes and with it understanding. There are now numerous cancer vaccine programs in development. However, F-stein locked into his position and never wavered in his belief that cancer vaccines don’t work. With F-stein, I have seen that if new information emerges over time that challenges his view, he ignores it.)

 

December 11, 2013  AF Comments on Seeking Alpha article entitled Northwest Biotherapeutics: An Analysis of Its Transforming Balance Sheet Restructuring by Smith on Stocks

All I can say is don't be like the other poor schmoes who actually believe in dendritic cancer vaccines. They don't work. Enjoy trading your NWBO. Perhaps Smith will write a few more articles to ensnare the next greater fool into buying. But remember, Linda can't delay the blowup forever. It's coming.

Smith -- Have you figured out now that dendritic cancer vaccines don't work? Today's it's IMUC fail, NWBO coming soon. Nice job.

 

February 16, 2017 AF Tweet  I'm sure you already know I don't believe in any of the cancer vaccine technology NWBO is developing. DCVax L and Direct will surely fail and never be approved. There's no reason to believe otherwise. All the Linda Powers/Cognate self-enrichment stuff is fun, but the fundamental bear thesis against NWBO is based on the impotence of the DCVax platform.

It's late. I'll get into details later.

(SmithOnStocks comment: He never comes back later or ever to explain. As he so often does, he presents a definitive conclusion based on undisclosed facts or no facts at all)

 

January 12, 2016 AF Tweet   DCVax does not target neo-antigens. Whoever told you that is ignorant or lying.

(SmithOnStocks comment:  As I went to great lengths to explain and as Dr. Ashkans emphasized, it is the precise targeting of neoantigens that is the most exciting feature of DCVax-L. This is game, set match for exposing F-stein’s fundamental ignorance and we could just move on. However, I will continue with other comments to put more nails in his coffin of ignorance.)

 

August 12, 2014   The Street.Com article entitled Northwest Bio DC-Vax Study Changes Hint at Failure    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.

(SmithOnStocks comment: He has never written anything that would explain the thinking behind this comment. Most likely because there is none.)

 

May 29, 2014 AF Comment on Seeking Alpha article entitled Northwest Biotherapeutics: Management Discusses Interim Data on Phase I/II Trial of DCVax-Direct by  SmithOnStocks

Larry, my friend... let me try to explain this to you in the simplest of terms. Dendritic cells are already in the body and aren't capable of recognizing the tumor antigens. That is why these people have cancer! (Well, one reason, not the only, but let's not digress.)

With DCVax-Direct, the only thing NWBO is doing is removing the ineffectual dendritic cells from white blood cells and then re-injecting them back into the same patient. That's it! This is the idiot's approach to immunotherapy, which is why NWBO is trying it, and you believe it.

At least with DC-Vax, NWBO is bathing the dendritic cells with the tumor antigens ex-vivo and then re-injecting. This approach won't work either, but at least it makes a teeny tiny bit of sense.

(SmithOnStocks Comment: The statement that NWBO is removing ineffective dendritic cells and then reinjecting them shows his total ignorance. As I pointed out in my explanation, the manufacturing of DCVax-L and DCVax Direct starts with removing monocytes from the blood and then differentiating monocytes into immature dendritic cells. In the case of DCVax-L the immature dendritic cell is loaded with neoantigen ex vivo and in the case of DCVax Direct in vivo. The end result is an entirely new dendritic cell loaded with neoantigens. F-stein falsely maintains that they are just recycling dendritic cells. )

 

October 9, 2014  AF Comment on Seeking Alpha article entitled Northwest Bio's Latest Financing Abuses Its Shareholders: Is the Charade Over? by Biotech Hawk

DCVax-Direct is simply a slurry of off-the-shelf, un-modified dendritic cells injected into a tumor. You could probably inject grapefruit juice into the tumor and get the same result.

Thanks for letting me know the latest NWBO bull thesis. It's even more pathetic than I ever realized.

(SmithOnStocks Comment: This further emphasizes F-stein’s ignorance. I have already discussed that he is confused in saying that dendritic cells are injected. He confounds his ignorance by saying they are off the shelf (allogeneic). No Adam, the living cells used by DCVax-L and DCVax Direct are based on autologous cells. If there were such a thing as off the shelf dendritic cells from donors, it would cause an autoimmune reaction.)

 

May 20, 2016 AF Comment on Investor Hub

Sure, comparing DCVax Direct to grapefruit juice is a tad hyperbolic, but not much. Removing DCs from a patient to "mature" them and re-injecting the same DCs back into the patient isn't going to have any significant effect on the tumor. These DCs were already unable to see the tumor cells. NWBO is not doing anything with Direct to change that.

It's an absurd project

 

June 10, 2014   AF Comment on Seeking Alpha article entitled Inovio Pharmaceuticals Could Outperform - Dr. J. Joseph Kim, CEO, Tells Us Why by Arrow Loop Research

Dendritic cells are already present in white blood cells and ARE NOT RECOGNIZING the tumor. Taking them out and putting them back in is not doing anything useful. The only instance where a dendritic cell vaccine has worked is Provenge, and that's because the dendritic cells were primed ex-vivo to recognize the one antigen in prostate cancer that appears to play a major role in the disease. Dendreon got lucky. Provenge would not work if it was simply expanded dendritic cells re-injected back into the body.

It is absurd to believe the dendritic cells in DCVAX-Direct are going to magically attach themselves to antigen simply because you inject the tumor.

 

May 28, 2014 AF Comment on Seeking Alpha article entitled Northwest Biotherapeutics: Management Discusses Interim Data on Phase I/II Trial of DCVax-Direct by SmithOnStocks

Most absurd, but entirely lost on mindless simpletons who own NWBO, is the fact that DC-VAX Direct consists of dendritic cells removed from a patient's blood, which are then re-injected into a tumor, where they are supposed to magically pick up tumor antigens and kick off an immune system storm to kill the same tumor.

This is the stuff of loony-bin fantasies.

December 23, 2015 AF Comment on Investor Hub

You’re confusing “good” cancer immunotherapies i.e. checkpoint inhibitors with “bad” cancer immunotherapies i.e. old, tired dendritic cell vaccines like DCVax. The latter will not find a place in medicine because they’re impotent.

No one is trying to slow down NWBO. The company has done this on its own, in large part because no one is interested in their technology.

(SmithOnStocks comment: I was interested)

 

February 16, 2017 AF Tweet

I'm sure you already know I don't believe in any of the cancer vaccine technology NWBO is developing. DCVax L and Direct will surely fail and never be approved. There's no reason to believe otherwise. All the Linda Powers/Cognate self-enrichment stuff is fun, but the fundamental bear thesis against NWBO is based on the impotence of the DCVax platform.

It's late. I'll get into details later.

(SmithOnStocks, comment   I think he uses the last line in order to avoid having to justify his statement. He never gets into details.)

 

August 12, 2014  TheStreet.Com  Northwest Bio DC-Vax Study Changes Hint at Failure

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.

(SmithOnStocks Comment: He never explains how he dug deeper to reach this conclusion.)

 

 

 

 


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