Northwest Biotherapeutics (OTCMKTS: NWBO) is now a risk-off biotech trading at a significant discount; in a “sell the news” market, there are no more milestones to sell as the company completed its phase 3 trial successfully and met its primary endpoint. The well-known architect of the sell-off is none other than STAT Reporter Adam Feuerstein. His usual MO is: “the company missed the endpoint and they cherry-picked the data in post hoc analysis.” What is so amazing about this latest STAT News concoction criticizing NWBO is that the company nailed its phase 3 primary endpoint and its glioblastoma drug is a likely candidate for approval. Investors should be dismissing this “washed up” reporter with epic fails on his pick list. NWBO is extremely undervalued for a company that has a treatment that could very well become the standard of care for glioblastoma patients after a 17 year hiatus since the last advance in treatment for these cancer sufferers. NWBO is scaling up manufacturing in anticipation of approval and the epitaph on Feuerstein’s Reporting Career could read “Another 10-year fight Settled with FDA Approval.”
Examples of Feuerstein's Pans About Endpoints
Feuerstein has been neurotic about commenting on topline data readouts but for the past 10 years he has been infatuated with NWBO with only a brief affair with CytoDyn (OTCMKTS: CYDY), and now he is back to NWBO. We cannot forget about Cel-Sci Corporation (NYSE: CVM) as Feuerstein reminisces. CytoDyn Missed primary Endpointshttps://twitter.com/adamfeuerstein/status/1367973561722363907Amarin Missed Primary Endpointshttps://twitter.com/adamfeuerstein/status/1196467252897423365Anavex Changed Primary and Secondary Endpointshttps://twitter.com/adamfeuerstein/status/1488483211428704263BridgeBio Misses Primary Endpointhttps://twitter.com/adamfeuerstein/status/1475447582184910854?lang=enAmpio No Better than Salinehttps://twitter.com/adamfeuerstein/status/948254479656374273Keen investors can see his obvious pattern, in that he coordinates his attacks on these biotechs around the timing of the announcements. Now the good news for NWBO investors is that there are no more announcements except the potential drama of an FDA advisory panel. This is probably the last hurrah for Feuerstein with respect to NWBO, but you never know because he has defined his career claiming how utterly worthless the technology is. There has got to be one more punch left in him. The only real chance he has to save face is if another technology magically rushes in to become the standard of care. It is highly unlikely but possible if you follow the galectin science in oncology, but then he’d be rooting for his nemesis Galectin Therapeutics (NASDAQ: GALT) that he panned early in his career and the company currently isn’t anywhere near this disease indication in cancer.
Feuersteins Track Record on Auto Destruct
The game of musical chairs is about to end for Feuerstein and he goes into the twilight of his career. A number of FDA approvals in companies he has attacked should be hitting the news wires in the coming years. His unprecedented attack on CYDY should be resolved with an HIV BLA submission and subsequent approval in 2023 provided NWBO doesn’t steal the show first. Cytokinetics Failed Primary Endpoint and 4-5 Secondary Endpointshttps://twitter.com/adamfeuerstein/status/621014107446226944 A huge blemish on Feuerstein’s track record is his pan of Cytokinetics (NASDAQ: CYTK). Back in 2015 he thoroughly bashed the science and here they are, seven years later with a $3.3 billion market cap and huge returns for patient investors. Long term investors that listened to him missed out on a 13X return over 7 years. Feuerstein is far from infallible as he would have investors believe and his influence has been waning as investors see his clearly biased and uneducated responses lacking solid scientific basis. Could it be his Political Science degree, or just laziness? Time will tell. His recent showing at ASCO, the premiere oncology industry conference, bordered on desperation as he approached NWBO shareholders in this following encounter. Feuerstein's tactics are well documented. He bullies CEOs, doctors, and patients in clinical trials, and here he was basically caught on camera spewing lies to investors. The man depicted clearly has no shame, and just look at how he dressed for ASCO. You have to love the “Feuerstein flab” that investors highlighted on Twitter. Investors have to ask themselves if they would entrust their hard-earned money to this pathetic individual in the mask?
Feuerstein’s May 10th Attacks
In a typical fashion, Feuerstein attacked on Twitter and also in an article in STAT News on May 10th after NWBO’s release of their phase 3 glioblastoma data. As usual, he did little to no analysis, but legions of his followers started shorting and selling the stock. NWBO shares slid after releasing its phase 3 topline results for its immunotherapeutic vaccine treatment (DCVax-L) for patients with glioblastoma (GBM), whereby the multinational, 331 patient study met its primary and secondary endpoints. Patients in the drug arm exhibited a marked increase in overall survival, a gold standard of efficacy in a clinical trial like this. Feuerstein based his career on attacking companies for missing their primary endpoints in clinical trials. Many times science requires adjusting what is being measured in order to be able to identify clinical effects. This happens a majority of the time making it easy for him to maintain a winning track record in order to prey on small biotechs. In the case of NWBO he cannot even claim that they missed their primary endpoint because they very clearly hit it.NWBO has been Feuerstein’s pet project since 2014 in what many believe to be a stock manipulation scheme. His first attacks on Twitter misrepresented NWBO’s phase 3 clinical trial design enhancements as a conspiracy to move the bullseye after they saw a grouping of outcomes. He has published over 20 negative articles on the company.His Twitter attack focused on how the company was supposedly doing post-hoc analysis and changed the endpoints using the historical changes feature on clinicaltrials.gov. The crux of his online attack was published in his STAT article, which examined the meaningless endpoint of progression free survival, an endpoint the company reasonably jettisoned. What makes Feuerstein’s attack on this company so reprehensible is that this is potentially the first systemic treatment improvement for GBM patients since 2005, when Temodar was approved for newly-diagnosed GBM, adding a mere 2.5 months of survival. In 1995, the Gliadel wafer was approved for recurrent GBM and offered patients only 2 months additional survival. Treatment options for GBM are dismal.
Meeting Primary and Secondary Endpoints
Debunking the attack was Neurosurgeon Keyoumars Ashkan, Professor of Neurosurgery & Lead for Oncology. He is a well-respected neurosurgeon in the UK and viewed the Phase 3 trial results are an incredible step forward in treating both newly diagnosed and recurrent GBM
Autologous Tumor Lysate-Loaded Dentritic Cell Vaccination for Glioblastoma (DCVax)
“We cannot use progression-free survival to look at these patients because it's totally pointless. What you are seeing on the scan is not necessarily tumor changes, it could simply be the effect of treatment. It could actually be a good thing rather than a bad thing, and clearly, it's been nonsense to use a biomarker of response when it is totally false from the outset.“
Northwest Biotherapeutics’ DCVax-L and Phase 3 Trial
NWBO’s phase 3 clinical trial was a resounding success because it met its primary endpoint, median overall survival (p<0.002), for newly diagnosed glioblastoma, but the Feuerstein Mob is attempting to distort the fact that the vaccine was found to be efficacious by convoluting the truth. Investors need to know the details to identify his deception. So first let's examine the phase 3 trial and then what Feuerstein claimed, and why it’s wrong.NWBO’s GBM vaccine is comprised of a patient's autologous dendritic cells cultured in tumor cell lysate, allowing for a potent immune reaction. These trained cells are then reinjected intradermally into the patient to attack any residual cancer cells and/or prevent a recurrence. The company’s phase 3 trial took GBM patients through standard of care—surgery and chemo—before starting treatment with DCVax-L or placebo.
DCVax-L Phase 3 Topline Results Presentation
The trial initially used a crossover design to make it worth it for the patients who would have to undergo invasive procedures to obtain their blood samples but then might get placebo treatment. When these placebo patients progressed, they would cross over to obtain the vaccine. Because of this, the endpoint was progression-free survival (PFS) and not overall survival, which would be convoluted by the crossover design—PFS can be measured before the crossover and OS cannot, for those crossover patients.This trial started before immunotherapy was really gaining acceptance, and before the concept of pseudoprogression was identified as a potential issue in measuring PFS. Pseudoprogression is often associated with favorable outcomes but initially causes the tumor to grow because it means that the tumor is being infiltrated with immune cells that are beginning to identify it and attack it, causing it to swell. The secondary endpoint, progression free survival, was not met, but that is actually a good thing because it is common in this disease for the tumor to get bigger before it gets smaller due to pseudoprogression—the growth of tumor size due to significant infiltration of immune cells attacking the tumor. Attracting immune cells is the hallmark of the treatment actually working which means if it works its going to cause inflammation at the tumor site and that will be picked up in the imaging. That blip up in tumor size means the treatment is working but that temporary increase in tumor size still stops the clock on the progression free survival measurement. This effect in NWBO’s trial was widely expected so any shock value implied by the short mafia is just drama and an attempt to confuse investors. Handbook of Neuro-Oncology Neuroimaging (Second Edition). Chapter 55 - Pseudoprogression in Neuro-Oncology: Overview, Pathophysiology, and InterpretationSince the crossover arm couldn’t be used as placebo, NWBO gathered data from a variety of other recent trials, using contemporaneous patient data, closely matched using an array of criteria, in newly diagnosed as well as recurrent GBM. They performed sensitivity analyses as well as adjustments for patient characteristics, and in each case the clinical result was the same. 1,366 nGBM and 640 rGBM patients were used in total for placebo, making the comparison very robust.The outcome of the trial was that DCVax-L increased mOS from 16.5 months to 19.3 months for nGBM, with a survival tail (the few patients that do survive much longer) of 13% versus 5.7%. In recurrent GBM, mOS increased from 7.8 to 13.2 months, with a survival tail of 11.1% versus 5.1% at 30 months after recurrence. All of this was accomplished withough the safety issues that might make patients want to forego standard-of-care therapy; there was no cytokine storm or autoimmune reactions, and only 5 serious adverse events potentially related to the vaccine. According to the analysis, the long-term survivors had consistent immune memory (T-cell) phenotypes, potentially changing the natural history of GBM from a uniformly fatal to a chronic, manageable disease for these patients.
More About Glioblastoma
GBM is a disease that is aggressive, heterogeneous, and immunologically “cold” (the immune system will typically not recognize the tumor and deal with it, so developing a therapy for the disease is very difficult; the heterogeneity additionally makes any type of targeted therapy difficult and this is potentially why NWBO’s personalized vaccine is a better approach.Standard of Care (SOC) for GBM is still stuck in the dark ages of cancer therapy as patients typically undergo surgery and 6 weeks of daily chemo and radiation, transitioning to monthly chemo, only to be brought to the brink of death to survive another 16 months on average with very poor quality of life. Given the aggressive nature of GBM and the immunological ignorance of its existence, the tumors tend to recur 7-8 months later (near 100% recurrence rate), whereby the patient has another 8 months to live. In summary, treatment is almost ineffective and quality of life is extremely poor. 5-year survival is less than 5%. A new treatment is desperately needed; in the 2005-2016 timeframe, there were 417 clinical trials for GBM, with only 16 phase 3 trials, and one positive phase 3 trial (a device, not a drug). Since 2016, more approaches have failed, including CAR-T therapies, checkpoint inhibitors, peptide vaccines, gene therapy, chemo, and dendritic cells with standardized peptides.Compared to these almost ineffective treatment options that offer a year or two of poor-quality life to patients, NWBO's results really stand out as it offers significantly more time to the patients without the safety risks. So wait, how could Feuerstein convolute this? He just makes up lies!
Feuerstein’s Flabs
Feuerstein made up a bunch of lies in his hit piece; not all of them are even worth reviewing, but certain ones stand out:First, Feuerstein implies that DCVax missed its primary endpoint of PFS (the old endpoint), by saying that the treatment performed worse than placebo, ignoring the concept of pseudoprogression:
“Patients administered the Northwest Bio Treatment, called DCVax, went a median 6.2 months without their brain tumors returning compared to a median of 7.6 months for patients offered a placebo.”
This is not correct. Residual cancer progressed in size, not full-blown recurrence. The PFS threshold was met but the primary endpoint measures overall survival, whereby the patients receiving treatment did better and survived longer.Feuerstein's second flab stated that the company simply threw out the placebo arm when in reality the placebo patients went to the crossover arm, the recurrent GBM part of the study:
“The company discarded the overall survival data from the 99 patients randomized to treatment with a placebo. Those original, prespecified data were thrown out, and replaced on a post-hoc basis with survival data collected from 1,366 patients who participated in five entirely separate and previously completed clinical trials.”
There are two flabs within this flab. The first is simple; the placebo data were not thrown out. Due to the clinical trial design explained earlier in this article, the placebo patients were later enrolled in the rGBM arm and therefore couldn’t be used for long-term placebo analysis. As such, the company used external control, analyzed by an independent third party. The other sneaky fib in this statement was that the analysis was post-hoc. This technically isn’t true since the analysis plan was run past regulatory authorities before unblinding the data.Feuerstein's final flab was implying that NWBO concocted an alternate reality with the data, showing their trial was a success. However, over 40 trial investigators involved in the phase 3 trial signed affidavits certifying the honesty of the results.This kind of blatant lying was likely taught to Feuerstein when Jim Cramer hired him when he worked for TheStreet.com. There is an infamous interview with Cramer from over a decade ago where he explains how funds manipulate shares using fear tactics and misinformation. Distorting the truth is Feuerstein’s bread and butter.The only negative to the trial was its misrepresentation in the fraudulent media. The trial was a resounding success and the short mafia, and perhaps some investors willing to believe the lies, are the only reasons shares are down.
Investment Summary
It’s an amazing phenomenon to see that Feuerstein's tactics are still effective in this day and age of social media. Investors at NWBO are infuriated that he gets away with telling his alternative facts. The unfortunate fact is that his legion of followers is bigger than NWBO zealots. We hope this article exposes the washed-out biotech commentator for who he really is. He’s a cyber bully—plain and simple. Investors should study his demeanor at ASCO and how his track record costs both investors and patients in the long run. His tactics are tiring and his track record is going to be under serious attack as FDA approvals start rolling in on the companies he has panned over the years. His analysis is a joke because it's a preplanned attack in advance. He preys on investors’ fears, getting them to sell first and ask questions later. NWBO has a very high likelihood of getting DCVax approved. The timing of potential approval is unknown, but the drug is slated to change the Standard of Care (SOC) in glioblastoma, both newly diagnosed and recurrent. Investors with a little bit of patience could see a multibillion-dollar valuation (perhaps up to $7 billion dollars) in the coming months to years just as Novocure (NASDAQ: NVCR) saw after succeeding in glioblastoma with its device (as opposed to a systemic treatment). The company is commercializing its operations and scaling up manufacturing. The overall slump in biotech may be depressing prices but much of the risk in NWBO is gone. The high likelihood of approval, the neutralization of Feuerstein, and the ramping of manufacturing are elements of a sunny outlook for NWBO. The stock is at extremely oversold levels and every share that is bought and held is another nail in Feuerstein's biotech coffin.
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Disclosure: Insider Financial and its owners do not have a position in the stocks posted and have posted this article for free without editorial input. This article was written by a guest contributor and solely reflects his opinions.
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