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On the day that $nwbo reported at the NYAS(dr.mulholland zoom) exemplary dc vax L trial results, 5/10/22, Adam Feuerstein reported on Stat News " NWBO’s drug “perform[ed] worse than a placebo.”.
CITADEL , et al, SITE ADAM FEUERSTEIN RESEARCH IN THEIR COURT LISTENER STATEMENT:
“For example, NWBO asserts in conclusory fashion that much of the purported spoofing occurred on May 10, 2022, when NWBO’s stock declined despite supposedly “excellent news” about a drug trial. ¶ 73. But it is not surprising—or suggestive of fraudulent intent—that there was significant interest in selling NWBO stock on May 10, 2022, given reporting that NWBO’s drug “perform[ed] worse than a placebo.”” [1]
https://courtlistener.com/docket/66579590/northwest-biotherapeutics-inc-v-canaccord-genuity-llc/
ON 7/25/24 THE SEC AND DOJ CAUGHT UP WITH ANDREW LEFT.
"Through these reports and tweets, Left exploited his Citron Research platform by taking the following steps. First, Left established long or short exposure in the target company through equity shares and/or options. Next, Left issued reports and tweets informing his readers or leading them to believe that he had long or short exposure in the target company. Left then recommended that his readers trade in the same direction as his positions. Finally, in many cases, Left gave his readers a purported price target, i.e., a share price at which the stock would trade. Following Left’s reports and tweets, the price of these target stocks moved on average more than 12%. Unbeknownst to the market, however, Left planned to capitalize on those price movements and quickly reverse his own positions in the equity shares and options – which he had induced readers to follow – but at prices far higher (or lower) than the price targets Left had pushed to his readers and the marketplace. In other words, Left bought back the stock almost immediately after telling his readers to sell, and Left sold stock almost immediately after telling his readers to buy. This fraudulent practice deceived investors and allowed Left to use his Citron Research reports and tweets as catalysts from which he could derive short-term profits. Left directed this trading in furtherance of the scheme through his personal accounts and accounts in the name of his entity, Defendant Citron Capital, LLC (“Citron Capital”), generating millions in profits. "
https://nytimes.com/2024/07/26/business/andrew-left-short-seller-fraud.html…
https://justice.gov/usao-cdca/media/1361671/dl?inline… (doj complaint)
https://sec.gov/files/litigation/complaints/2024/comp-pr2024-89.pdf…. (sec complaint)
⚾️SWING AND A MISS: Market Maker(s) & Hedge Fund(s) failure to properly set up their scapegoat, Adam Feuerstein⚾️$NWBO filed a lawsuit against seven market makers accusing them of illegally spoofing NWBO’s stock. Spoofing is a way to illegally manipulate a stock price either up… pic.twitter.com/ij7xbI2ReN
— hoffmann6383 (@hoffmann6383) May 3, 2024
$nwbo @alphavestcap @SmithOnStocks1 @BrianEgolf2 @hoffmann6383 @metacollectiveG @ATLnsider
— alphavestcapital.com (@alphavestcap) July 27, 2024
"Explanation of How Adam Feuerstein Has Egregiously Misrepresented the Results of the Phase 3 Trial of DCVax-L"
"Shares of Virtu Financial are down more than 3% after the electronic…
Fri, Jul 26, 2024, 6:05 PM
(Bloomberg) -- Trampled by markets and attacked by angry executives, short sellers now find themselves confronting their biggest worry yet: the US government.
Fresh accusations by federal authorities that one of the industry’s most prominent players, Andrew Left, committed securities fraud is sending shock waves across the already shrinking field of investors who specialize in betting against specific stocks. For a group that has long courted controversy by taking on some of the biggest names in business, it’s a particularly sobering moment.
The US government has spent years digging into the industry’s practices, but as inquiries by Justice Department and the Securities and Exchange Commission went quiet in recent months, many began assuming the probes had fizzled. Even Left, who pulled back after investigators seized his computers and phones, got back into the game.
That all changed Friday.
Prosecutors announced criminal charges against him, while the SEC brought a civil lawsuit — cases that could upend his firm, Citron, and send him to prison for years.
According to the SEC, Left generated about $20 million in profits from illegal trading involving almost two dozen companies. Prosecutors accused him of repeatedly misleading the public — taking issue with what they called his “sensationalized” reports and describing times when he indicated he would keep bets going much further, when he was already in the process of taking winnings off the table.
At one point, Left bragged to colleagues that some of his public statements caused retail investors to trade the way he wanted them to and that it was like taking “candy from a baby,” according to the SEC.
Other short sellers and their supporters were quick to argue Friday that the alleged misconduct was unique to Left and shouldn’t be seen as a broad rebuke of bearish investing.
Still, some said, it may make it harder for short sellers to find financial backers. Some predicted they may have to spend more on legal advice and temper their public statements.
‘Defective Theory’
Left’s attorney attacked the government’s case, saying it all rested on a “defective theory” that the investor had a duty to specify his trading plans beyond disclosing that he was active in the market. The lawyer warned that the charges will have a chilling effect on bearish research, hurting public investors by leaving corporate malfeasance unexposed.
“The fact that the Mr. Left trades in the securities he researches and writes about is well known to everyone, and there is no rule or law requiring a publisher who discloses that he is trading to also publish his private trading intentions,” the attorney, James Spertus, said in an emailed statement. “The allegations filed today should concern all investors because the publication of truthful information is critical to efficient markets.”
Short sellers have attracted a growing number of antagonists over the past decade. Executives atop targeted companies have persuaded some shareholders that bearish investors were the real bad actors. Academics chimed in with research showing activists were crossing the line into “smash and grab” tactics, knocking down stocks down and then unwinding their bets before the public could figure out who’s right. Lawmakers held hearings on Capitol Hill.
The Justice Department’s indictment and the SEC’s complaint is now providing fresh fodder for critics.
“For far too long short sellers have benefited from regulatory neglect as enforcers have been fearful they might discourage the occasional legitimate whistleblower,” said Paul Pelletier, a former federal prosecutor who has represented a company targeted by a short seller.
The government’s cases seek to draw legal lines around what kind of speech amounts to market manipulation in an era in which small investors and hedge fund managers openly debate their views on social media platforms and online message boards. The SEC noted that Left and Citron command a “substantial following” online with more than 100,000 followers on Twitter alone. The problem, authorities said, was that Left used such platforms to deceive the public.
The Justice Department accused him, for example, of announcing “extreme target prices” for some stocks he was analyzing while concealing his intent to exit those positions long before the securities reached those levels.
“To profit from the intended price movement triggered by Citron’s reports and tweets, defendant Left covered all or substantially all of the positions he held in a targeted security, often within hours — and sometimes minutes — after publication,” according to the indictment.
Left has been publishing reports and touting bearish bets for more than 17 years. He made a name for himself by pointing out accounting irregularities in Chinese companies that had flocked to US markets. Prosecutors said he would often provide commentary on business news channels including CNBC, Fox Business and Bloomberg Television.
He has previously estimated he had published around 200 reports over the years. Well over a dozen of the companies he targeted were later delisted or filed for bankruptcy. In a sign of the complicated relationship between shorts and regulators, US authorities followed up on some of his research by bringing civil or criminal charges against executives at companies he targeted.
Examples include Valeant Pharmaceuticals, which Left accused of being at the center of an illicit sales scheme. After then-US Attorney Preet Bharara announced charges in 2016 against two executives linked to the company, he referenced the role that investor websites and news organizations played.
Paltry Profits
Yet the business of short selling has only gotten tougher in recent years. Some bears struggled against the updraft of the long bull market that began after the 2008 financial crisis. Then came the advent of meme-stock trading during the pandemic, with retail investors organizing counter attacks on bets against GameStop and other struggling companies.
Short-selling profits can be tiny even if a well-researched report rocks the market. Nate Anderson’s look at Adani Group last year erased as much as $153 billion of market value, yet Anderson said in a statement this month that he reaped just over $4 million on the trade.
And even then, such paltry gains can then be wiped away as short sellers face the cost of lawsuits and, now, government probes.
Jim Chanos, perhaps the best-known and longest-running short seller, turned his firm into a family office late last year after assets dropped to less than $200 million.
“Investors — primarily institutional investors — have just given up on the fact that there’s going to be excess returns on the short side,” Chanos said about the decision to close down. “People just didn’t want to invest.”
--With assistance from Stephanie Stoughton.
https://x.com/kshaughnessy2/status/1817027540336410959
@kshaughnessy2
Who is next? What names will Andrew Left give up?
Remember at the Archegos trial when former colleagues turned on each other?
"..The US government has spent years digging into the industry’s practices, but as inquiries by Justice Department and the Securities and Exchange Commission went quiet in recent months, many began assuming the probes had fizzled.
Even Left, who pulled back after investigators seized his computers and phones, got back into the game.
That all changed Friday.
Prosecutors announced criminal charges against him, while the SEC brought a civil lawsuit — cases that could upend his firm, Citron, and send him to prison for years.....
....At one point, Left bragged to colleagues that some of his public statements caused retail investors to trade the way he wanted them to and that it was like taking “candy from a baby,” according to the SEC...."
https://finance.yahoo.com/news/short-sellers-feel-heat-us-220543133.html
#AndrewLeft
In the complaint against short seller Andrew Left
Anson Advisors and Anson Funds Management are listed under "Related Persons and Entities"
Who are Hedge Funds 1 and 2?
Who is Business Associate One?
Who is Portfolio Manager One?
And which small research firm is designated as the Third Party Intermediary ?
https://sec.gov/files/litigation/complaints/2024/comp-pr2024-89.pdf
#AndrewLeft #Citron
The DOJ indicted Andrew Left today based in part on the first quote below (1). In the second quote(2) , Larry Smith describes Adam Feuerstain's 5/10/22 short attack on $nwbo that sent the stock from $2.10 the day before to $0.38 on the 10th. Like Left , on 5/10/22, Feuerstein could have coordinated the release of his short report that day on the dc vax l trial results , released also on 5/10/22 ,with many hedge funds . Let's recall that the trade volume on 5/10/22 was 77 million shares, up appreciably from average daily volume of 1.5 million shares.
https://nytimes.com/2024/07/26/business/andrew-left-short-seller-fraud.html
https://justice.gov/usao-cdca/media/1361671/dl?inline (doj complaint)
https://sec.gov/files/litigation/complaints/2024/comp-pr2024-89.pdf. (sec complaint)
1) "Defendant LEFT coordinated with hedge funds to disseminate short reports and information to be posted on Twitter, coordinated with hedge funds regarding the timing of publication, and enabled the hedge funds to trade in the Targeted Securities before the reports were disseminated. In exchange for sharing his planned announcements with the hedge funds in advance of posting them publicly, the hedge funds paid defendant LEFT a portion of their trading profits."
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174819848
2) F-stein wrote an article during or shortly after the NYAS presentation on May 10, 2022 that falsely stated that the phase 3 trial of DCVax-L failed. This drew an indignant and angry response from Dr. Steven Toms, a board certified neurosurgeon at Rhode Island who participated in the trial and has had very positive experiences with patients he has treated with DCVax-L. He absolutely torched F-stein’s attacks on DCVax-L in a series of tweets that challenge tweets from F-stein and hedge fund employees. This interchange between Dr. Toms and F-stein shines a remarkable light on how F-stein gaslights DCVax-L. Here are the tweets from Dr. Toms.
https://smithonstocks.com/explanation-of-how-adam-feuerstein-has-egregiously-misrepresented-the-results-of-the-phase-3-trial-of-dcvax-l/
Explanation of How Adam Feuerstein Has Egregiously Misrepresented the Results of the Phase 3 Trial of DCVax-L
POSTED by LARRY SMITH on NOV 22, 2022 • (0)
Tagged as DCVax-L phase 3 trial, Refuting Adam Feuerstein's misrepresentation that DCVax-L phase 3 Trial failed + Categorized as Company Reports, LinkedInExecutive SummaryI have tried to make this report as short and readable as possible so that in many cases I provide links to a previous article I have written or other pertinent data, rather than recreating the information in this report. So, you will find lots of links. The intent is to give the reader my conclusions in short form in this executive summary, but also to provide access to in-depth information for those seeking more detail.Adam Feuerstein and his employer, Stat News, continue to falsely allege that the phase 3 trial of DCVax-L failed. This is a jaw dropping accusation given that:The 70 plus investigators who participated in the trial co-authored a paper describing the phase 3 trial and its results and concluding that the trial had successfully reached its primary endpoint of median overall survival (mOS) in newly diagnosed glioblastoma (ndGBM) and the secondary endpoint of mOS in recurrent glioblastoma (rGBM).
The prestigious New York Academy of Science featured a presentation at its conference on May 10, 2022 in which the presenter unequivocally stated that the trial successfully reached its primary and secondary endpoints. This was the first time that unblinded topline data from the trial was made public.
On November 17, 2022 JAMA Oncology, a Journal of the American Medical Association publication, printed a peer reviewed article clearly stating that the trial successfully reached its endpoints. This was, of course, based on the paper co-authored by the 70 plus investigators’
On November 23, 2022 the lead investigator in the trial, Linda Liau, was invited to make a presentation at a plenary session of the prestigious Society of Neuro-Oncology in which she stated that the trial was successful. SNO is the foremost medical conference for neuro surgeons and others involved in the treatment of glioblastoma. The decision to prominently feature Dr. Liau’s presentation speaks volumes about how many physicians will view these results.
These are very powerful endorsements for the view that DCVax-L holds the promise of extending survival and represents a significant medical advance in the treatment of GBM, a disease in which half of patients die within roughly 16 months of diagnosis and only 5% survive for five years. The phase 3 data shows that DCVax-L added to current standard of care impressively increases survival in ndGBM. Also shown in this trial was that DCVax-L added to SOC is the first therapy ever shown to increase survival in rGBM. Having said that, I must emphasize that while these endorsements give me very strong confidence that DCVax-L will be approved by regulatory agencies, they are not a lock solid guarantee.I believe that F-stein’s argument that the trial failed are clearly false. Let me take on and debunk his primary arguments one at a timeHe makes the serious allegation that Northwest looked at the data from the phase 3 trial in an interim look in 2014 and saw that the trial had failed. This is just wrong. The interim look was conducted by an independent group, the Data Monitoring Committee, and the Company remained blinded until the data lock in October of 2020. Only the DMC and FDA saw the data.
Having falsely concluded that NWBO conclusively knew that the trial had failed, he alleges that the Company changed the endpoint from progression free survival to median overall survival. He is correct that the endpoint was changed, but for very understandable and legitimate reasons. This is explained in an eloquent manner on pages 8 and 9 of the Statistical Analysis Plan (SAP) that is an integral part of the phase 3 trial. Please refer to this link to the SAP for that comprehensive explanation.
It is completely legitimate for a Company to change the endpoints of a trial if the study remains blinded to the Company which is clearly the case and if the statistical analysis plan is submitted to regulatory agencies prior to data lock and unblinding which is also the case. Again this is explained on pages 8 and 9 of the SAP that I just referred to.
F-Stein repeatedly and falsely claims that progression free survival (PFS) was the primary endpoint of the trial. A quick glance at http://ClinTrials.gov shows that PFS was not even a secondary endpoint. See this link. The primary endpoint is clearly stated as mOS in ndGBM and the secondary endpoint is mOS in rGBM. Both endpoints were achieved with strong strong significance. Nevertheless, he repeats and repeats that PFS was the primary endpoint.
I would also point out that PFS which is based on tumor expansion is a surrogate endpoint. Overall survival is the gold standard measure for oncology trials. OS as a data point can’t be manipulated or cherry picked as death is an absolute event. Somehow, F-stein has persuaded himself that determining whether a tumor expands is a better measure of outcome for the trial than how long the patient survives. He makes the curious argument that even though patients are achieving medically meaningful, longer survival with DCVax-L that we should ignore this and focus on tumor expansion which is only an indirect marker of survival to determine if the trial was successful.
The company was forced by the nature of the trial to use external controls. This is the one aspect of the trial which draws the most scrutiny and on which F-stein focused. The most common practice in clinical trials is to compare a group given the drug to a control group not given the drug. Again see the previously cited pages 8 and 9 of the SAP for details on why Northwest chose to use historical controls.
F-stein alleges that the FDA will not accept external controls, but there is strong precedent that the agency will do so. The medically exciting CAR-T drugs Kymriah, Yescarta, Tecartis, Breyanzi, Abcema and Carvytki were all recently approved on the basis of phase 2 trials in which there was no control group and in which their results were referenced to external controls. It is also important to note that they were also approved on the basis of objective response rates (i.e. tumor shrinkage which was not accompanied by any data on duration of effect) rather than the much cleaner, more informative endpoint of survival. I would argue that the FDA would very likely approve DCVax-L as it did the CAR-T drugs without the use of external controls. However, the use of external controls makes for an even stronger argument for approval.
Indeed, there was a time when the FDA was not receptive to external controls in clinical trials, but this has changed. The example of the CAR-T drugs is illustrative. Also, there was an article entitled “External control arms in oncology: current use and future directions” that was published in Annals of Oncology January, 2022 by Dr. Richard Pazdur and 12 colleagues from the FDA. See this liThis article lays out situations in which the use of external controls might be appropriate and the steps companies should take if they wish to use external controls. NWBO believes that its SAP which was developed two years prior to this article closely fits the criteria laid out.
Richard Pazdur, M.D., one of the authors of the Annals paper, is the director of the FDA's Oncology Center of Excellence (OCE), which leverages the combined skills of the FDA's regulatory scientists and reviewers with expertise in drugs, biologics and devices to expedite the development of novel cancer products. In his role as director of the OCE, Pazdur is responsible for leading the effort to develop and execute an integrated regulatory approach to enhance the cross-center coordination of oncology product clinical review. He will likely be a key person at the FDA in determining whether DCVax-L is approved.
F-stein References Physicians who Express Skepticism on the Trial Results; Let’s Put This in PerspectiveBefore going further, I want to disassemble the cheap trick F-stein employs in his November 21, 2022 note in finding physicians who are skeptical about the DCVax-L phase 3 study. In his article he cites the opinion of Dr. Chen who is chair of the neurosurgery department at the University of Minnesota School of Medicine and was not involved in the DCVax study.F-stein says he asked Dr. Chen to review the DCVax study published in JAMA Oncology. Dr, Chen also attended the annual meeting of the Society of Neuro-Oncology (SNO), where the data were presented last Sunday. F-stein claimed that Dr. Chen said: The authors should be congratulated for conducting a study of this magnitude,” but the results are uninterpretable because the analysis was not pre-specified when the study was started in 2007. Importantly, Dr, Chen has no clinical experience with DCVax-L Also, he is in error in stating that the analysis shown in the SAP was not pre-specified.Likewise, F-stein reached out to Dr. Donald O’Rourke, a professor of neurosurgery at the University of Pennsylvania, for his opinion of the DCVax study. F-stein states that he also attended the SNO meeting. F-stein reported that Dr. O’Rourke stated via e-mail, a list of confounding issues related to patient enrollment and the conduct of the study that makes him skeptical. He also has no clinical experience with http://DCVax-L.It is more than interesting to note that Dr. Steven Brem is also a professor of neurosurgery at the University of Pennsylvania and is the third physician listed behind the lead investigators on the phase 3 trial, Dr. Linda Liau and Dr. Keyoumers Ashkans, as a co-author of the phase 3 DCVax-L study. He has extensive clinical experience with DCVax-L. In a presentation at SNO on November 20, 2022 he said that the results published in JAMA were extremely exciting. Dr. Brem, who has seen DCVax-L’s effects in his own patients, considers DCVax-L a major http://advance.It is totally to be expected that you can find physicians who are skeptical of this or any study. I re-emphasize that neither of F-stein’s physician references has treated any patients with DCVax-L and neither has had any involvement with DCVax-L clinical programs. In contrast, Drs. Liau, Ashkans and Brem have many years of experience with DCVax-L.F-stein wrote an article during or shortly after the NYAS presentation on May 10, 2022 that falsely stated that the phase 3 trial of DCVax-L failed. This drew an indignant and angry response from Dr. Steven Toms, a board certified neurosurgeon at Rhode Island who participated in the trial and has had very positive experiences with patients he has treated with DCVax-L. He absolutely torched F-stein’s attacks on DCVax-L in a series of tweets that challenge tweets from F-stein and hedge fund employees. This interchange between Dr. Toms and F-stein shines a remarkable light on how F-stein gaslights DCVax-L. Here are the tweets from Dr. Toms.May 11 1:55 PMStevenToms11 Replying to MidwestHedgie and adamfeuerstein and 4 othersAs a neurosurgical oncologist who has spent his career working against this disease and the father of a cancer survivor it is nauseating to see you and your ilk diminish the life’s work of my colleague (Linda Liau) for a quick Buck. The data’s imperfections do not diminish the results.May 11, 2022 8:52 PMStevenToms11No immunotherapy (vaccine or ICB) has worked in GBM as the CNS is immunologically privileged. DCVax has overcome the immunosuppressive environment and is the 2nd clinical trial recently to reach significance in GBM. More to do but a good step forward. (A trial of the TTF medical device Optune developed by Novocure was the first)May 12, 2022 6:30 AMReplying to
@adamfeuerstein
and @MidwestHedgieSo when will MidwestHedgie and adamfeuerstein come look my patients in the eye and tell them they cannot have a therapy with 20+ years of investigation, a $1B clinical trial and backing of the oncology community then I will engage them again. Otherwise it is just noise.May 12, 2022 9:58 AMReplying to adamfeuerstein and MidwestHedgieRepeating your lies do not make them truths. In all of your clinical experience Dr. Feuerstein can you point me to all of your long term survivors who got another therapy and lived this long? Just one that was not IDH1 mutant please. I will wait.May 18, 2022 8:27 amReplying to @adamfeuersteinI see Dr. Feuerstein is back to protect patients from the clinicians who performed the study and actually care for patients with GBM. You have my name and know I am not anonymous so please stop your falsehoods. End points were changed as we began to understand pseudoprogression.May 18, 2022 8:42 AMReplying to adamfeuersteinSuccess against a plague like GBM is not presto! It is a long slog of discovery and many ideas over decades that fail to move the needle on survival. Oncologists will not ignore a scientifically sound nontoxic therapy that addresses multiple tumor antigens and improves survivalMay 19, 2022 7:57 AMReplying to @adamfeuersteinI see the pathological lying about the data continues. Before I head to surgery I was wondering if you had the dignity or data to reply to my earlier challenges to your lies. Waiting for a cogent response to why anyone would care about PFS in immune therapyMay 26, 2022 12:53 PMReplying to
@Hygro10
and @adamfeuersteinGBMs do not live more than 5 years other than those treated with DCVax or TTF. I have patients 5+ year survival treated on both protocols. I have zero long term survivors in 25 years of practice without. Do the math. The p value is highly significant.May 27, 2022 2:08 PMToms11Steven@Hygro10 and @adamfeuersteinJust emailed by Communications office at my university that a Mr. Feuerstein has emailed them to inquire about the veracity of this handle. If you think you can intimidate me or that I will remain silent while you impugn this work you are sadly incorrect.This last tweet from Dr, Toms is beyond alarming. F-stein has been accused of trying to intimidate doctors who speak positively on DCVax-L. This would be consistent with allegations on Twitter that F-stein intimidated Linda Liau and UCLA to prevent her from giving the presentation at NYAS. She was originally scheduled to do so, but unexpectedly cancelled. He is also alleged to have tried unsuccessfully to convince the New York Academy of Sciences to drop the presentation. This caused them to ban F-stein from attending the conference. How Stat News can support this behavior is not understandable to me.If you stop now, you can generally understand why I believe that F-stein’s arguments are without any merit. Let me now go on to discuss in more detail, the reasons why I believe that the F-stein position is demonstrably false.Investigators in the Phase 3 Study Believe That DCVax-L Is a Major AdvanceF-stein’s allegations put him in the curious position of challenging the credibility and integrity of the two lead investigators in the trial, both of whom believe that DCVax-L meaningfully extends survival in patients they have treated with DCVax-L. They are:Dr. Linda Liau is the lead investigator in the US. She is Chair of the Department of Neurosurgery at UCLA, Professor, Department of Neurosurgery, UCLA David Geffen School of Medicine and Director, Brain Tumor Program, UCLA David Geffen School of Medicine. She was formerly Editor-in-Chief of the Journal of Neuro-Oncology. Her research efforts are focused on the molecular biology of brain tumors, gene therapy, immunotherapy, and brain cancer vaccines. Dr. Liau is a highly respected neuro-surgeon.Dr. Keyoumers Ashkan is the chief investigator for the European segment of the phase 3 DCVax-L trial. He is the clinical lead for neuro-oncology at King's College Hospital in the UK. 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.Both of these physicians have impeccable credentials and also many years of hands on hands on experience with DCVax-L not only in the phase 3 trial, but also in patients receiving DCVax-L in compassionate use. In addition, there were 70 physicians who participated in the phase 3 trial have signed as co-authors who support the JAMA Oncology paper..New York Academy of Sciences (NYAS) Conference Highlights DCVax-LThe NYAS proudly states that for over 200 years, it has brought together extraordinary people working at the frontiers of discovery. It has become an important and widely-respected contributor to the international scientific community. To drive scientific progress, the Academy hosts over 150 conferences and symposia annually, connecting experts across sectors, disciplines, and national boundaries. Research presented at the Academy is disseminated globally via in-person and virtual events, the prestigious Annals of the New York Academy of Sciences, and a broad array of digital http://media.At the May 10, 2022 meeting of the NYAS, topline data from the completed phase 3 trial of DCVax-L was selected for presentation. Promising, blinded interim data had previously been reported but this was the first time that the final topline data was presented. NYAS editors first reviewed that data and after concluding that this was an important study then asked external experts to peer review the trial. This was a rigorous process intended to establish the accuracy and credibility of the study.The study was presented by Dr. Mulholland, an investigator in the phase 3 trial. Representing the other 70 plus physicians in the trial, he stated that the trial had successfully met the primary endpoint of median overall survival in newly diagnosed glioblastoma with a highly significant p value of <0.002. It was also successful in reaching the secondary endpoint of median overall survival in recurrent GBM with a p value of <0.001. He believes that DCVax-L is a major advance in the treatment of both ndGBM and rGBM.JAMA Oncology, A Publication of the American Medical Association Publishes Peer Reviewed Article on Phase 3 StudyIn a November 17, 2022 edition of JAMA Oncology, a peer reviewed article was published that concurred with Dr. Liau, Dr. Ashkans and 70 other investigators in the study along with the NYAS that the trial had successfully reached the primary endpoint of mOS in ndGBM and secondary endpoint of mOS in rGBM. This is the most powerful validation of the results that we can hope for. I describe the internal and external experts that looked at all aspects of the clinical data and the statistical analysis used to interpret it. I describe this in detail in my recent article. See this link.Linda Liau Presents Phase 3 Results at the Society of Neuro-OncologyOn November 23, 2022, the lead investigator in the trial, Linda Liau, was invited to make a presentation at a plenary session of the Society of Neuro-Oncology in which she stated that the trial was successful. SNO is the foremost medical conference for neuro surgeons and others involved in the treatment of glioblastoma. Needless to say, this plenary presentation is another powerful endorsement of the hypothesis that DCVax-L is a significant advance in the treatment of http://glioblastoma.Now Let’s Look at F-stein.F-stein has no scientific background but boasts a degree in political science. 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 (this is especially the case for a living cell product)? Of course you would. Failing this, everything else he says is meaningless or highly questionable. On June 20, 2022 I wrote an article entitled Adam Feuerstein Investigates Adam Feuerstein’s Understanding of Dendritic Cell Vaccines. See this http://link.In searching through the plethora of articles he has written on Northwest Biotherapeutics, I was unable to find anything remotely resembling an in-depth analysis of dendritic cell vaccines or DCVax-L. 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 http://TheStreet.com. 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.After reading this linked article, I think you will concur that F-stein is utterly clueless on understanding the technology. So how does he come up with his articles? Who does he depend on? F-stein hasn’t shared his sources with us. However, he has expressed great admiration for certain hedge funds. A September 27, 2014 article was published in the Washington Post entitled Northwest Biotherapeutics stock woes highlight the harm of short sales executed by hedge funds. See this link. This article suggests a link between F-stein and short selling. I have no way of knowing if the Washington Post article is accurate and I am not alleging collusion, but this article is in the public record and investors can draw their own conclusions.Turning to Two Superficial Articles Written by Adam Feuerstein and Published by Stat NewsF-stein wrote an article on May 10, 2022 that was published in Stat News during or shortly after the NYAS presentation in which he falsely stated that the trial had failed to reach the primary endpoint which he falsely stated was progression free survival instead of median overall survival. I wrote a refutation of that article entitled Debunking Silly, Fictitious Adam Feuerstein Article Falsely Claiming Phase 3 Trial of DCVax-L in Glioblastoma Multiforme Was a Failure. Here is the link.On November 21, F-stein published a second article. This was essentially a rehash of the May 10 article so I won’t bother to refute it.
https://justice.gov/usao-cdca/media/1361671/dl?inline (doj complaint)
https://sec.gov/files/litigation/complaints/2024/comp-pr2024-89.pdf. (sec complaint)
"Prominent Short Seller Made Millions Off Bait-and-Switch Scheme, U.S. Says
Federal authorities filed charges against Andrew Left, founder of Citron Research, who they said made at least $16 million from a multiyear scheme to manipulate market prices."
https://nytimes.com/2024/07/26/business/andrew-left-short-seller-fraud.html
👍 0
10:41 PM · Jul 26, 2024
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Short Sellers Feel Heat After US Charges Andrew Left With Fraud
Tom Schoenberg and Katherine Burton
Fri, Jul 26, 2024, 6:05 PM EDT6 min read
10
(Bloomberg) -- Trampled by markets and attacked by angry executives, short sellers now find themselves confronting their biggest worry yet: the US government.
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Fresh accusations by federal authorities that one of the industry’s most prominent players, Andrew Left, committed securities fraud is sending shock waves across the already shrinking field of investors who specialize in betting against specific stocks. For a group that has long courted controversy by taking on some of the biggest names in business, it’s a particularly sobering moment.
The US government has spent years digging into the industry’s practices, but as inquiries by Justice Department and the Securities and Exchange Commission went quiet in recent months, many began assuming the probes had fizzled. Even Left, who pulled back after investigators seized his computers and phones, got back into the game.
That all changed Friday.
Prosecutors announced criminal charges against him, while the SEC brought a civil lawsuit — cases that could upend his firm, Citron, and send him to prison for years.
According to the SEC, Left generated about $20 million in profits from illegal trading involving almost two dozen companies. Prosecutors accused him of repeatedly misleading the public — taking issue with what they called his “sensationalized” reports and describing times when he indicated he would keep bets going much further, when he was already in the process of taking winnings off the table.
At one point, Left bragged to colleagues that some of his public statements caused retail investors to trade the way he wanted them to and that it was like taking “candy from a baby,” according to the SEC.
Other short sellers and their supporters were quick to argue Friday that the alleged misconduct was unique to Left and shouldn’t be seen as a broad rebuke of bearish investing.
Still, some said, it may make it harder for short sellers to find financial backers. Some predicted they may have to spend more on legal advice and temper their public statements.
‘Defective Theory’
Left’s attorney attacked the government’s case, saying it all rested on a “defective theory” that the investor had a duty to specify his trading plans beyond disclosing that he was active in the market. The lawyer warned that the charges will have a chilling effect on bearish research, hurting public investors by leaving corporate malfeasance unexposed.
“The fact that the Mr. Left trades in the securities he researches and writes about is well known to everyone, and there is no rule or law requiring a publisher who discloses that he is trading to also publish his private trading intentions,” the attorney, James Spertus, said in an emailed statement. “The allegations filed today should concern all investors because the publication of truthful information is critical to efficient markets.”
Short sellers have attracted a growing number of antagonists over the past decade. Executives atop targeted companies have persuaded some shareholders that bearish investors were the real bad actors. Academics chimed in with research showing activists were crossing the line into “smash and grab” tactics, knocking down stocks down and then unwinding their bets before the public could figure out who’s right. Lawmakers held hearings on Capitol Hill.
The Justice Department’s indictment and the SEC’s complaint is now providing fresh fodder for critics.
“For far too long short sellers have benefited from regulatory neglect as enforcers have been fearful they might discourage the occasional legitimate whistleblower,” said Paul Pelletier, a former federal prosecutor who has represented a company targeted by a short seller.
The government’s cases seek to draw legal lines around what kind of speech amounts to market manipulation in an era in which small investors and hedge fund managers openly debate their views on social media platforms and online message boards. The SEC noted that Left and Citron command a “substantial following” online with more than 100,000 followers on Twitter alone. The problem, authorities said, was that Left used such platforms to deceive the public.
The Justice Department accused him, for example, of announcing “extreme target prices” for some stocks he was analyzing while concealing his intent to exit those positions long before the securities reached those levels.
“To profit from the intended price movement triggered by Citron’s reports and tweets, defendant Left covered all or substantially all of the positions he held in a targeted security, often within hours — and sometimes minutes — after publication,” according to the indictment.
Left has been publishing reports and touting bearish bets for more than 17 years. He made a name for himself by pointing out accounting irregularities in Chinese companies that had flocked to US markets. Prosecutors said he would often provide commentary on business news channels including CNBC, Fox Business and Bloomberg Television.
He has previously estimated he had published around 200 reports over the years. Well over a dozen of the companies he targeted were later delisted or filed for bankruptcy. In a sign of the complicated relationship between shorts and regulators, US authorities followed up on some of his research by bringing civil or criminal charges against executives at companies he targeted.
Examples include Valeant Pharmaceuticals, which Left accused of being at the center of an illicit sales scheme. After then-US Attorney Preet Bharara announced charges in 2016 against two executives linked to the company, he referenced the role that investor websites and news organizations played.
Paltry Profits
Yet the business of short selling has only gotten tougher in recent years. Some bears struggled against the updraft of the long bull market that began after the 2008 financial crisis. Then came the advent of meme-stock trading during the pandemic, with retail investors organizing counter attacks on bets against GameStop and other struggling companies.
Short-selling profits can be tiny even if a well-researched report rocks the market. Nate Anderson’s look at Adani Group last year erased as much as $153 billion of market value, yet Anderson said in a statement this month that he reaped just over $4 million on the trade.
And even then, such paltry gains can then be wiped away as short sellers face the cost of lawsuits and, now, government probes.
Jim Chanos, perhaps the best-known and longest-running short seller, turned his firm into a family office late last year after assets dropped to less than $200 million.
“Investors — primarily institutional investors — have just given up on the fact that there’s going to be excess returns on the short side,” Chanos said about the decision to close down. “People just didn’t want to invest.”
--With assistance from Stephanie Stoughton.
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The DOJ indicted Andrew Left today based in part on the first quote below (1). In the second quote(2) , Larry Smith describes Adam Feuerstain's 5/10/22 short attack on $nwbo that sent the stock from $2.10 the day before to $0.38 on the 10th. Like Left , on 5/10/22, Feuerstein could have coordinated the release of his short report that day on the dc vax l trial results , released also on 5/10/22 ,with many hedge funds . Let's recall that the trade volume on 5/10/22 was 77 million shares, up appreciably from average daily volume of 1.5 million shares.
https://nytimes.com/2024/07/26/business/andrew-left-short-seller-fraud.html
https://justice.gov/usao-cdca/media/1361671/dl?inline (doj complaint)
https://sec.gov/files/litigation/complaints/2024/comp-pr2024-89.pdf. (sec complaint)
1) "Defendant LEFT coordinated with hedge funds to disseminate short reports and information to be posted on Twitter, coordinated with hedge funds regarding the timing of publication, and enabled the hedge funds to trade in the Targeted Securities before the reports were disseminated. In exchange for sharing his planned announcements with the hedge funds in advance of posting them publicly, the hedge funds paid defendant LEFT a portion of their trading profits."
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174819848
2) F-stein wrote an article during or shortly after the NYAS presentation on May 10, 2022 that falsely stated that the phase 3 trial of DCVax-L failed. This drew an indignant and angry response from Dr. Steven Toms, a board certified neurosurgeon at Rhode Island who participated in the trial and has had very positive experiences with patients he has treated with DCVax-L. He absolutely torched F-stein’s attacks on DCVax-L in a series of tweets that challenge tweets from F-stein and hedge fund employees. This interchange between Dr. Toms and F-stein shines a remarkable light on how F-stein gaslights DCVax-L. Here are the tweets from Dr. Toms.
https://smithonstocks.com/explanation-of-how-adam-feuerstein-has-egregiously-misrepresented-the-results-of-the-phase-3-trial-of-dcvax-l/
Explanation of How Adam Feuerstein Has Egregiously Misrepresented the Results of the Phase 3 Trial of DCVax-L
POSTED by LARRY SMITH on NOV 22, 2022 • (0)
Tagged as DCVax-L phase 3 trial, Refuting Adam Feuerstein's misrepresentation that DCVax-L phase 3 Trial failed + Categorized as Company Reports, LinkedInExecutive SummaryI have tried to make this report as short and readable as possible so that in many cases I provide links to a previous article I have written or other pertinent data, rather than recreating the information in this report. So, you will find lots of links. The intent is to give the reader my conclusions in short form in this executive summary, but also to provide access to in-depth information for those seeking more detail.Adam Feuerstein and his employer, Stat News, continue to falsely allege that the phase 3 trial of DCVax-L failed. This is a jaw dropping accusation given that:The 70 plus investigators who participated in the trial co-authored a paper describing the phase 3 trial and its results and concluding that the trial had successfully reached its primary endpoint of median overall survival (mOS) in newly diagnosed glioblastoma (ndGBM) and the secondary endpoint of mOS in recurrent glioblastoma (rGBM).
The prestigious New York Academy of Science featured a presentation at its conference on May 10, 2022 in which the presenter unequivocally stated that the trial successfully reached its primary and secondary endpoints. This was the first time that unblinded topline data from the trial was made public.
On November 17, 2022 JAMA Oncology, a Journal of the American Medical Association publication, printed a peer reviewed article clearly stating that the trial successfully reached its endpoints. This was, of course, based on the paper co-authored by the 70 plus investigators’
On November 23, 2022 the lead investigator in the trial, Linda Liau, was invited to make a presentation at a plenary session of the prestigious Society of Neuro-Oncology in which she stated that the trial was successful. SNO is the foremost medical conference for neuro surgeons and others involved in the treatment of glioblastoma. The decision to prominently feature Dr. Liau’s presentation speaks volumes about how many physicians will view these results.
These are very powerful endorsements for the view that DCVax-L holds the promise of extending survival and represents a significant medical advance in the treatment of GBM, a disease in which half of patients die within roughly 16 months of diagnosis and only 5% survive for five years. The phase 3 data shows that DCVax-L added to current standard of care impressively increases survival in ndGBM. Also shown in this trial was that DCVax-L added to SOC is the first therapy ever shown to increase survival in rGBM. Having said that, I must emphasize that while these endorsements give me very strong confidence that DCVax-L will be approved by regulatory agencies, they are not a lock solid guarantee.I believe that F-stein’s argument that the trial failed are clearly false. Let me take on and debunk his primary arguments one at a timeHe makes the serious allegation that Northwest looked at the data from the phase 3 trial in an interim look in 2014 and saw that the trial had failed. This is just wrong. The interim look was conducted by an independent group, the Data Monitoring Committee, and the Company remained blinded until the data lock in October of 2020. Only the DMC and FDA saw the data.
Having falsely concluded that NWBO conclusively knew that the trial had failed, he alleges that the Company changed the endpoint from progression free survival to median overall survival. He is correct that the endpoint was changed, but for very understandable and legitimate reasons. This is explained in an eloquent manner on pages 8 and 9 of the Statistical Analysis Plan (SAP) that is an integral part of the phase 3 trial. Please refer to this link to the SAP for that comprehensive explanation.
It is completely legitimate for a Company to change the endpoints of a trial if the study remains blinded to the Company which is clearly the case and if the statistical analysis plan is submitted to regulatory agencies prior to data lock and unblinding which is also the case. Again this is explained on pages 8 and 9 of the SAP that I just referred to.
F-Stein repeatedly and falsely claims that progression free survival (PFS) was the primary endpoint of the trial. A quick glance at http://ClinTrials.gov shows that PFS was not even a secondary endpoint. See this link. The primary endpoint is clearly stated as mOS in ndGBM and the secondary endpoint is mOS in rGBM. Both endpoints were achieved with strong strong significance. Nevertheless, he repeats and repeats that PFS was the primary endpoint.
I would also point out that PFS which is based on tumor expansion is a surrogate endpoint. Overall survival is the gold standard measure for oncology trials. OS as a data point can’t be manipulated or cherry picked as death is an absolute event. Somehow, F-stein has persuaded himself that determining whether a tumor expands is a better measure of outcome for the trial than how long the patient survives. He makes the curious argument that even though patients are achieving medically meaningful, longer survival with DCVax-L that we should ignore this and focus on tumor expansion which is only an indirect marker of survival to determine if the trial was successful.
The company was forced by the nature of the trial to use external controls. This is the one aspect of the trial which draws the most scrutiny and on which F-stein focused. The most common practice in clinical trials is to compare a group given the drug to a control group not given the drug. Again see the previously cited pages 8 and 9 of the SAP for details on why Northwest chose to use historical controls.
F-stein alleges that the FDA will not accept external controls, but there is strong precedent that the agency will do so. The medically exciting CAR-T drugs Kymriah, Yescarta, Tecartis, Breyanzi, Abcema and Carvytki were all recently approved on the basis of phase 2 trials in which there was no control group and in which their results were referenced to external controls. It is also important to note that they were also approved on the basis of objective response rates (i.e. tumor shrinkage which was not accompanied by any data on duration of effect) rather than the much cleaner, more informative endpoint of survival. I would argue that the FDA would very likely approve DCVax-L as it did the CAR-T drugs without the use of external controls. However, the use of external controls makes for an even stronger argument for approval.
Indeed, there was a time when the FDA was not receptive to external controls in clinical trials, but this has changed. The example of the CAR-T drugs is illustrative. Also, there was an article entitled “External control arms in oncology: current use and future directions” that was published in Annals of Oncology January, 2022 by Dr. Richard Pazdur and 12 colleagues from the FDA. See this liThis article lays out situations in which the use of external controls might be appropriate and the steps companies should take if they wish to use external controls. NWBO believes that its SAP which was developed two years prior to this article closely fits the criteria laid out.
Richard Pazdur, M.D., one of the authors of the Annals paper, is the director of the FDA's Oncology Center of Excellence (OCE), which leverages the combined skills of the FDA's regulatory scientists and reviewers with expertise in drugs, biologics and devices to expedite the development of novel cancer products. In his role as director of the OCE, Pazdur is responsible for leading the effort to develop and execute an integrated regulatory approach to enhance the cross-center coordination of oncology product clinical review. He will likely be a key person at the FDA in determining whether DCVax-L is approved.
F-stein References Physicians who Express Skepticism on the Trial Results; Let’s Put This in PerspectiveBefore going further, I want to disassemble the cheap trick F-stein employs in his November 21, 2022 note in finding physicians who are skeptical about the DCVax-L phase 3 study. In his article he cites the opinion of Dr. Chen who is chair of the neurosurgery department at the University of Minnesota School of Medicine and was not involved in the DCVax study.F-stein says he asked Dr. Chen to review the DCVax study published in JAMA Oncology. Dr, Chen also attended the annual meeting of the Society of Neuro-Oncology (SNO), where the data were presented last Sunday. F-stein claimed that Dr. Chen said: The authors should be congratulated for conducting a study of this magnitude,” but the results are uninterpretable because the analysis was not pre-specified when the study was started in 2007. Importantly, Dr, Chen has no clinical experience with DCVax-L Also, he is in error in stating that the analysis shown in the SAP was not pre-specified.Likewise, F-stein reached out to Dr. Donald O’Rourke, a professor of neurosurgery at the University of Pennsylvania, for his opinion of the DCVax study. F-stein states that he also attended the SNO meeting. F-stein reported that Dr. O’Rourke stated via e-mail, a list of confounding issues related to patient enrollment and the conduct of the study that makes him skeptical. He also has no clinical experience with http://DCVax-L.It is more than interesting to note that Dr. Steven Brem is also a professor of neurosurgery at the University of Pennsylvania and is the third physician listed behind the lead investigators on the phase 3 trial, Dr. Linda Liau and Dr. Keyoumers Ashkans, as a co-author of the phase 3 DCVax-L study. He has extensive clinical experience with DCVax-L. In a presentation at SNO on November 20, 2022 he said that the results published in JAMA were extremely exciting. Dr. Brem, who has seen DCVax-L’s effects in his own patients, considers DCVax-L a major http://advance.It is totally to be expected that you can find physicians who are skeptical of this or any study. I re-emphasize that neither of F-stein’s physician references has treated any patients with DCVax-L and neither has had any involvement with DCVax-L clinical programs. In contrast, Drs. Liau, Ashkans and Brem have many years of experience with DCVax-L.F-stein wrote an article during or shortly after the NYAS presentation on May 10, 2022 that falsely stated that the phase 3 trial of DCVax-L failed. This drew an indignant and angry response from Dr. Steven Toms, a board certified neurosurgeon at Rhode Island who participated in the trial and has had very positive experiences with patients he has treated with DCVax-L. He absolutely torched F-stein’s attacks on DCVax-L in a series of tweets that challenge tweets from F-stein and hedge fund employees. This interchange between Dr. Toms and F-stein shines a remarkable light on how F-stein gaslights DCVax-L. Here are the tweets from Dr. Toms.May 11 1:55 PMStevenToms11 Replying to MidwestHedgie and adamfeuerstein and 4 othersAs a neurosurgical oncologist who has spent his career working against this disease and the father of a cancer survivor it is nauseating to see you and your ilk diminish the life’s work of my colleague (Linda Liau) for a quick Buck. The data’s imperfections do not diminish the results.May 11, 2022 8:52 PMStevenToms11No immunotherapy (vaccine or ICB) has worked in GBM as the CNS is immunologically privileged. DCVax has overcome the immunosuppressive environment and is the 2nd clinical trial recently to reach significance in GBM. More to do but a good step forward. (A trial of the TTF medical device Optune developed by Novocure was the first)May 12, 2022 6:30 AMReplying to
@adamfeuerstein
and @MidwestHedgieSo when will MidwestHedgie and adamfeuerstein come look my patients in the eye and tell them they cannot have a therapy with 20+ years of investigation, a $1B clinical trial and backing of the oncology community then I will engage them again. Otherwise it is just noise.May 12, 2022 9:58 AMReplying to adamfeuerstein and MidwestHedgieRepeating your lies do not make them truths. In all of your clinical experience Dr. Feuerstein can you point me to all of your long term survivors who got another therapy and lived this long? Just one that was not IDH1 mutant please. I will wait.May 18, 2022 8:27 amReplying to @adamfeuersteinI see Dr. Feuerstein is back to protect patients from the clinicians who performed the study and actually care for patients with GBM. You have my name and know I am not anonymous so please stop your falsehoods. End points were changed as we began to understand pseudoprogression.May 18, 2022 8:42 AMReplying to adamfeuersteinSuccess against a plague like GBM is not presto! It is a long slog of discovery and many ideas over decades that fail to move the needle on survival. Oncologists will not ignore a scientifically sound nontoxic therapy that addresses multiple tumor antigens and improves survivalMay 19, 2022 7:57 AMReplying to @adamfeuersteinI see the pathological lying about the data continues. Before I head to surgery I was wondering if you had the dignity or data to reply to my earlier challenges to your lies. Waiting for a cogent response to why anyone would care about PFS in immune therapyMay 26, 2022 12:53 PMReplying to
@Hygro10
and @adamfeuersteinGBMs do not live more than 5 years other than those treated with DCVax or TTF. I have patients 5+ year survival treated on both protocols. I have zero long term survivors in 25 years of practice without. Do the math. The p value is highly significant.May 27, 2022 2:08 PMToms11Steven@Hygro10 and @adamfeuersteinJust emailed by Communications office at my university that a Mr. Feuerstein has emailed them to inquire about the veracity of this handle. If you think you can intimidate me or that I will remain silent while you impugn this work you are sadly incorrect.This last tweet from Dr, Toms is beyond alarming. F-stein has been accused of trying to intimidate doctors who speak positively on DCVax-L. This would be consistent with allegations on Twitter that F-stein intimidated Linda Liau and UCLA to prevent her from giving the presentation at NYAS. She was originally scheduled to do so, but unexpectedly cancelled. He is also alleged to have tried unsuccessfully to convince the New York Academy of Sciences to drop the presentation. This caused them to ban F-stein from attending the conference. How Stat News can support this behavior is not understandable to me.If you stop now, you can generally understand why I believe that F-stein’s arguments are without any merit. Let me now go on to discuss in more detail, the reasons why I believe that the F-stein position is demonstrably false.Investigators in the Phase 3 Study Believe That DCVax-L Is a Major AdvanceF-stein’s allegations put him in the curious position of challenging the credibility and integrity of the two lead investigators in the trial, both of whom believe that DCVax-L meaningfully extends survival in patients they have treated with DCVax-L. They are:Dr. Linda Liau is the lead investigator in the US. She is Chair of the Department of Neurosurgery at UCLA, Professor, Department of Neurosurgery, UCLA David Geffen School of Medicine and Director, Brain Tumor Program, UCLA David Geffen School of Medicine. She was formerly Editor-in-Chief of the Journal of Neuro-Oncology. Her research efforts are focused on the molecular biology of brain tumors, gene therapy, immunotherapy, and brain cancer vaccines. Dr. Liau is a highly respected neuro-surgeon.Dr. Keyoumers Ashkan is the chief investigator for the European segment of the phase 3 DCVax-L trial. He is the clinical lead for neuro-oncology at King's College Hospital in the UK. 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.Both of these physicians have impeccable credentials and also many years of hands on hands on experience with DCVax-L not only in the phase 3 trial, but also in patients receiving DCVax-L in compassionate use. In addition, there were 70 physicians who participated in the phase 3 trial have signed as co-authors who support the JAMA Oncology paper..New York Academy of Sciences (NYAS) Conference Highlights DCVax-LThe NYAS proudly states that for over 200 years, it has brought together extraordinary people working at the frontiers of discovery. It has become an important and widely-respected contributor to the international scientific community. To drive scientific progress, the Academy hosts over 150 conferences and symposia annually, connecting experts across sectors, disciplines, and national boundaries. Research presented at the Academy is disseminated globally via in-person and virtual events, the prestigious Annals of the New York Academy of Sciences, and a broad array of digital http://media.At the May 10, 2022 meeting of the NYAS, topline data from the completed phase 3 trial of DCVax-L was selected for presentation. Promising, blinded interim data had previously been reported but this was the first time that the final topline data was presented. NYAS editors first reviewed that data and after concluding that this was an important study then asked external experts to peer review the trial. This was a rigorous process intended to establish the accuracy and credibility of the study.The study was presented by Dr. Mulholland, an investigator in the phase 3 trial. Representing the other 70 plus physicians in the trial, he stated that the trial had successfully met the primary endpoint of median overall survival in newly diagnosed glioblastoma with a highly significant p value of <0.002. It was also successful in reaching the secondary endpoint of median overall survival in recurrent GBM with a p value of <0.001. He believes that DCVax-L is a major advance in the treatment of both ndGBM and rGBM.JAMA Oncology, A Publication of the American Medical Association Publishes Peer Reviewed Article on Phase 3 StudyIn a November 17, 2022 edition of JAMA Oncology, a peer reviewed article was published that concurred with Dr. Liau, Dr. Ashkans and 70 other investigators in the study along with the NYAS that the trial had successfully reached the primary endpoint of mOS in ndGBM and secondary endpoint of mOS in rGBM. This is the most powerful validation of the results that we can hope for. I describe the internal and external experts that looked at all aspects of the clinical data and the statistical analysis used to interpret it. I describe this in detail in my recent article. See this link.Linda Liau Presents Phase 3 Results at the Society of Neuro-OncologyOn November 23, 2022, the lead investigator in the trial, Linda Liau, was invited to make a presentation at a plenary session of the Society of Neuro-Oncology in which she stated that the trial was successful. SNO is the foremost medical conference for neuro surgeons and others involved in the treatment of glioblastoma. Needless to say, this plenary presentation is another powerful endorsement of the hypothesis that DCVax-L is a significant advance in the treatment of http://glioblastoma.Now Let’s Look at F-stein.F-stein has no scientific background but boasts a degree in political science. 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 (this is especially the case for a living cell product)? Of course you would. Failing this, everything else he says is meaningless or highly questionable. On June 20, 2022 I wrote an article entitled Adam Feuerstein Investigates Adam Feuerstein’s Understanding of Dendritic Cell Vaccines. See this http://link.In searching through the plethora of articles he has written on Northwest Biotherapeutics, I was unable to find anything remotely resembling an in-depth analysis of dendritic cell vaccines or DCVax-L. 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 http://TheStreet.com. 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.After reading this linked article, I think you will concur that F-stein is utterly clueless on understanding the technology. So how does he come up with his articles? Who does he depend on? F-stein hasn’t shared his sources with us. However, he has expressed great admiration for certain hedge funds. A September 27, 2014 article was published in the Washington Post entitled Northwest Biotherapeutics stock woes highlight the harm of short sales executed by hedge funds. See this link. This article suggests a link between F-stein and short selling. I have no way of knowing if the Washington Post article is accurate and I am not alleging collusion, but this article is in the public record and investors can draw their own conclusions.Turning to Two Superficial Articles Written by Adam Feuerstein and Published by Stat NewsF-stein wrote an article on May 10, 2022 that was published in Stat News during or shortly after the NYAS presentation in which he falsely stated that the trial had failed to reach the primary endpoint which he falsely stated was progression free survival instead of median overall survival. I wrote a refutation of that article entitled Debunking Silly, Fictitious Adam Feuerstein Article Falsely Claiming Phase 3 Trial of DCVax-L in Glioblastoma Multiforme Was a Failure. Here is the link.On November 21, F-stein published a second article. This was essentially a rehash of the May 10 article so I won’t bother to refute it.
https://www.justice.gov/usao-cdca/media/1361671/dl?inline (doj complaint)
https://www.sec.gov/files/litigation/complaints/2024/comp-pr2024-89.pdf. (sec complaint)
"Prominent Short Seller Made Millions Off Bait-and-Switch Scheme, U.S. Says
Federal authorities filed charges against Andrew Left, founder of Citron Research, who they said made at least $16 million from a multiyear scheme to manipulate market prices."
https://www.nytimes.com/2024/07/26/business/andrew-left-short-seller-fraud.html
The DOJ indicted Andrew Left today based in part on the first quote below. In the second quote , Larry Smith describes Adam Feuerstain's 5/10/22 short attack on $nwbo that sent the stock from $2.10 the day before to $0.38 on the 10th. Like Left , on 5/10/22, Feuerstein could have coordinated the release of his short report that day on the dc vax l trial released also on 5/10/22 with many hedge funds . Let's recall that the trade volume on 5/10/22 was 77 million shares, up appreciably from average daily volume of 1.5 million shares.
https://nytimes.com/2024/07/26/business/andrew-left-short-seller-fraud.html
https://justice.gov/usao-cdca/media/1361671/dl?inline (doj complaint)
https://sec.gov/files/litigation/complaints/2024/comp-pr2024-89.pdf. (sec complaint)
"Defendant LEFT coordinated with hedge funds to disseminate short reports and information to be posted on Twitter, coordinated with hedge funds regarding the timing of publication, and enabled the hedge funds to trade in the Targeted Securities before the reports were disseminated. In exchange for sharing his planned announcements with the hedge funds in advance of posting them publicly, the hedge funds paid defendant LEFT a portion of their trading profits."
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174819848
F-stein wrote an article during or shortly after the NYAS presentation on May 10, 2022 that falsely stated that the phase 3 trial of DCVax-L failed. This drew an indignant and angry response from Dr. Steven Toms, a board certified neurosurgeon at Rhode Island who participated in the trial and has had very positive experiences with patients he has treated with DCVax-L. He absolutely torched F-stein’s attacks on DCVax-L in a series of tweets that challenge tweets from F-stein and hedge fund employees. This interchange between Dr. Toms and F-stein shines a remarkable light on how F-stein gaslights DCVax-L. Here are the tweets from Dr. Toms.
https://smithonstocks.com/explanation-of-how-adam-feuerstein-has-egregiously-misrepresented-the-results-of-the-phase-3-trial-of-dcvax-l/
Explanation of How Adam Feuerstein Has Egregiously Misrepresented the Results of the Phase 3 Trial of DCVax-L
POSTED by LARRY SMITH on NOV 22, 2022 • (0)
Tagged as DCVax-L phase 3 trial, Refuting Adam Feuerstein's misrepresentation that DCVax-L phase 3 Trial failed + Categorized as Company Reports, LinkedInExecutive SummaryI have tried to make this report as short and readable as possible so that in many cases I provide links to a previous article I have written or other pertinent data, rather than recreating the information in this report. So, you will find lots of links. The intent is to give the reader my conclusions in short form in this executive summary, but also to provide access to in-depth information for those seeking more detail.Adam Feuerstein and his employer, Stat News, continue to falsely allege that the phase 3 trial of DCVax-L failed. This is a jaw dropping accusation given that:The 70 plus investigators who participated in the trial co-authored a paper describing the phase 3 trial and its results and concluding that the trial had successfully reached its primary endpoint of median overall survival (mOS) in newly diagnosed glioblastoma (ndGBM) and the secondary endpoint of mOS in recurrent glioblastoma (rGBM).
The prestigious New York Academy of Science featured a presentation at its conference on May 10, 2022 in which the presenter unequivocally stated that the trial successfully reached its primary and secondary endpoints. This was the first time that unblinded topline data from the trial was made public.
On November 17, 2022 JAMA Oncology, a Journal of the American Medical Association publication, printed a peer reviewed article clearly stating that the trial successfully reached its endpoints. This was, of course, based on the paper co-authored by the 70 plus investigators’
On November 23, 2022 the lead investigator in the trial, Linda Liau, was invited to make a presentation at a plenary session of the prestigious Society of Neuro-Oncology in which she stated that the trial was successful. SNO is the foremost medical conference for neuro surgeons and others involved in the treatment of glioblastoma. The decision to prominently feature Dr. Liau’s presentation speaks volumes about how many physicians will view these results.
These are very powerful endorsements for the view that DCVax-L holds the promise of extending survival and represents a significant medical advance in the treatment of GBM, a disease in which half of patients die within roughly 16 months of diagnosis and only 5% survive for five years. The phase 3 data shows that DCVax-L added to current standard of care impressively increases survival in ndGBM. Also shown in this trial was that DCVax-L added to SOC is the first therapy ever shown to increase survival in rGBM. Having said that, I must emphasize that while these endorsements give me very strong confidence that DCVax-L will be approved by regulatory agencies, they are not a lock solid guarantee.I believe that F-stein’s argument that the trial failed are clearly false. Let me take on and debunk his primary arguments one at a timeHe makes the serious allegation that Northwest looked at the data from the phase 3 trial in an interim look in 2014 and saw that the trial had failed. This is just wrong. The interim look was conducted by an independent group, the Data Monitoring Committee, and the Company remained blinded until the data lock in October of 2020. Only the DMC and FDA saw the data.
Having falsely concluded that NWBO conclusively knew that the trial had failed, he alleges that the Company changed the endpoint from progression free survival to median overall survival. He is correct that the endpoint was changed, but for very understandable and legitimate reasons. This is explained in an eloquent manner on pages 8 and 9 of the Statistical Analysis Plan (SAP) that is an integral part of the phase 3 trial. Please refer to this link to the SAP for that comprehensive explanation.
It is completely legitimate for a Company to change the endpoints of a trial if the study remains blinded to the Company which is clearly the case and if the statistical analysis plan is submitted to regulatory agencies prior to data lock and unblinding which is also the case. Again this is explained on pages 8 and 9 of the SAP that I just referred to.
F-Stein repeatedly and falsely claims that progression free survival (PFS) was the primary endpoint of the trial. A quick glance at http://ClinTrials.gov shows that PFS was not even a secondary endpoint. See this link. The primary endpoint is clearly stated as mOS in ndGBM and the secondary endpoint is mOS in rGBM. Both endpoints were achieved with strong strong significance. Nevertheless, he repeats and repeats that PFS was the primary endpoint.
I would also point out that PFS which is based on tumor expansion is a surrogate endpoint. Overall survival is the gold standard measure for oncology trials. OS as a data point can’t be manipulated or cherry picked as death is an absolute event. Somehow, F-stein has persuaded himself that determining whether a tumor expands is a better measure of outcome for the trial than how long the patient survives. He makes the curious argument that even though patients are achieving medically meaningful, longer survival with DCVax-L that we should ignore this and focus on tumor expansion which is only an indirect marker of survival to determine if the trial was successful.
The company was forced by the nature of the trial to use external controls. This is the one aspect of the trial which draws the most scrutiny and on which F-stein focused. The most common practice in clinical trials is to compare a group given the drug to a control group not given the drug. Again see the previously cited pages 8 and 9 of the SAP for details on why Northwest chose to use historical controls.
F-stein alleges that the FDA will not accept external controls, but there is strong precedent that the agency will do so. The medically exciting CAR-T drugs Kymriah, Yescarta, Tecartis, Breyanzi, Abcema and Carvytki were all recently approved on the basis of phase 2 trials in which there was no control group and in which their results were referenced to external controls. It is also important to note that they were also approved on the basis of objective response rates (i.e. tumor shrinkage which was not accompanied by any data on duration of effect) rather than the much cleaner, more informative endpoint of survival. I would argue that the FDA would very likely approve DCVax-L as it did the CAR-T drugs without the use of external controls. However, the use of external controls makes for an even stronger argument for approval.
Indeed, there was a time when the FDA was not receptive to external controls in clinical trials, but this has changed. The example of the CAR-T drugs is illustrative. Also, there was an article entitled “External control arms in oncology: current use and future directions” that was published in Annals of Oncology January, 2022 by Dr. Richard Pazdur and 12 colleagues from the FDA. See this liThis article lays out situations in which the use of external controls might be appropriate and the steps companies should take if they wish to use external controls. NWBO believes that its SAP which was developed two years prior to this article closely fits the criteria laid out.
Richard Pazdur, M.D., one of the authors of the Annals paper, is the director of the FDA's Oncology Center of Excellence (OCE), which leverages the combined skills of the FDA's regulatory scientists and reviewers with expertise in drugs, biologics and devices to expedite the development of novel cancer products. In his role as director of the OCE, Pazdur is responsible for leading the effort to develop and execute an integrated regulatory approach to enhance the cross-center coordination of oncology product clinical review. He will likely be a key person at the FDA in determining whether DCVax-L is approved.
F-stein References Physicians who Express Skepticism on the Trial Results; Let’s Put This in PerspectiveBefore going further, I want to disassemble the cheap trick F-stein employs in his November 21, 2022 note in finding physicians who are skeptical about the DCVax-L phase 3 study. In his article he cites the opinion of Dr. Chen who is chair of the neurosurgery department at the University of Minnesota School of Medicine and was not involved in the DCVax study.F-stein says he asked Dr. Chen to review the DCVax study published in JAMA Oncology. Dr, Chen also attended the annual meeting of the Society of Neuro-Oncology (SNO), where the data were presented last Sunday. F-stein claimed that Dr. Chen said: The authors should be congratulated for conducting a study of this magnitude,” but the results are uninterpretable because the analysis was not pre-specified when the study was started in 2007. Importantly, Dr, Chen has no clinical experience with DCVax-L Also, he is in error in stating that the analysis shown in the SAP was not pre-specified.Likewise, F-stein reached out to Dr. Donald O’Rourke, a professor of neurosurgery at the University of Pennsylvania, for his opinion of the DCVax study. F-stein states that he also attended the SNO meeting. F-stein reported that Dr. O’Rourke stated via e-mail, a list of confounding issues related to patient enrollment and the conduct of the study that makes him skeptical. He also has no clinical experience with http://DCVax-L.It is more than interesting to note that Dr. Steven Brem is also a professor of neurosurgery at the University of Pennsylvania and is the third physician listed behind the lead investigators on the phase 3 trial, Dr. Linda Liau and Dr. Keyoumers Ashkans, as a co-author of the phase 3 DCVax-L study. He has extensive clinical experience with DCVax-L. In a presentation at SNO on November 20, 2022 he said that the results published in JAMA were extremely exciting. Dr. Brem, who has seen DCVax-L’s effects in his own patients, considers DCVax-L a major http://advance.It is totally to be expected that you can find physicians who are skeptical of this or any study. I re-emphasize that neither of F-stein’s physician references has treated any patients with DCVax-L and neither has had any involvement with DCVax-L clinical programs. In contrast, Drs. Liau, Ashkans and Brem have many years of experience with DCVax-L.F-stein wrote an article during or shortly after the NYAS presentation on May 10, 2022 that falsely stated that the phase 3 trial of DCVax-L failed. This drew an indignant and angry response from Dr. Steven Toms, a board certified neurosurgeon at Rhode Island who participated in the trial and has had very positive experiences with patients he has treated with DCVax-L. He absolutely torched F-stein’s attacks on DCVax-L in a series of tweets that challenge tweets from F-stein and hedge fund employees. This interchange between Dr. Toms and F-stein shines a remarkable light on how F-stein gaslights DCVax-L. Here are the tweets from Dr. Toms.May 11 1:55 PMStevenToms11 Replying to MidwestHedgie and adamfeuerstein and 4 othersAs a neurosurgical oncologist who has spent his career working against this disease and the father of a cancer survivor it is nauseating to see you and your ilk diminish the life’s work of my colleague (Linda Liau) for a quick Buck. The data’s imperfections do not diminish the results.May 11, 2022 8:52 PMStevenToms11No immunotherapy (vaccine or ICB) has worked in GBM as the CNS is immunologically privileged. DCVax has overcome the immunosuppressive environment and is the 2nd clinical trial recently to reach significance in GBM. More to do but a good step forward. (A trial of the TTF medical device Optune developed by Novocure was the first)May 12, 2022 6:30 AMReplying to
@adamfeuerstein
and @MidwestHedgieSo when will MidwestHedgie and adamfeuerstein come look my patients in the eye and tell them they cannot have a therapy with 20+ years of investigation, a $1B clinical trial and backing of the oncology community then I will engage them again. Otherwise it is just noise.May 12, 2022 9:58 AMReplying to adamfeuerstein and MidwestHedgieRepeating your lies do not make them truths. In all of your clinical experience Dr. Feuerstein can you point me to all of your long term survivors who got another therapy and lived this long? Just one that was not IDH1 mutant please. I will wait.May 18, 2022 8:27 amReplying to @adamfeuersteinI see Dr. Feuerstein is back to protect patients from the clinicians who performed the study and actually care for patients with GBM. You have my name and know I am not anonymous so please stop your falsehoods. End points were changed as we began to understand pseudoprogression.May 18, 2022 8:42 AMReplying to adamfeuersteinSuccess against a plague like GBM is not presto! It is a long slog of discovery and many ideas over decades that fail to move the needle on survival. Oncologists will not ignore a scientifically sound nontoxic therapy that addresses multiple tumor antigens and improves survivalMay 19, 2022 7:57 AMReplying to @adamfeuersteinI see the pathological lying about the data continues. Before I head to surgery I was wondering if you had the dignity or data to reply to my earlier challenges to your lies. Waiting for a cogent response to why anyone would care about PFS in immune therapyMay 26, 2022 12:53 PMReplying to
@Hygro10
and @adamfeuersteinGBMs do not live more than 5 years other than those treated with DCVax or TTF. I have patients 5+ year survival treated on both protocols. I have zero long term survivors in 25 years of practice without. Do the math. The p value is highly significant.May 27, 2022 2:08 PMToms11Steven@Hygro10 and @adamfeuersteinJust emailed by Communications office at my university that a Mr. Feuerstein has emailed them to inquire about the veracity of this handle. If you think you can intimidate me or that I will remain silent while you impugn this work you are sadly incorrect.This last tweet from Dr, Toms is beyond alarming. F-stein has been accused of trying to intimidate doctors who speak positively on DCVax-L. This would be consistent with allegations on Twitter that F-stein intimidated Linda Liau and UCLA to prevent her from giving the presentation at NYAS. She was originally scheduled to do so, but unexpectedly cancelled. He is also alleged to have tried unsuccessfully to convince the New York Academy of Sciences to drop the presentation. This caused them to ban F-stein from attending the conference. How Stat News can support this behavior is not understandable to me.If you stop now, you can generally understand why I believe that F-stein’s arguments are without any merit. Let me now go on to discuss in more detail, the reasons why I believe that the F-stein position is demonstrably false.Investigators in the Phase 3 Study Believe That DCVax-L Is a Major AdvanceF-stein’s allegations put him in the curious position of challenging the credibility and integrity of the two lead investigators in the trial, both of whom believe that DCVax-L meaningfully extends survival in patients they have treated with DCVax-L. They are:Dr. Linda Liau is the lead investigator in the US. She is Chair of the Department of Neurosurgery at UCLA, Professor, Department of Neurosurgery, UCLA David Geffen School of Medicine and Director, Brain Tumor Program, UCLA David Geffen School of Medicine. She was formerly Editor-in-Chief of the Journal of Neuro-Oncology. Her research efforts are focused on the molecular biology of brain tumors, gene therapy, immunotherapy, and brain cancer vaccines. Dr. Liau is a highly respected neuro-surgeon.Dr. Keyoumers Ashkan is the chief investigator for the European segment of the phase 3 DCVax-L trial. He is the clinical lead for neuro-oncology at King's College Hospital in the UK. 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.Both of these physicians have impeccable credentials and also many years of hands on hands on experience with DCVax-L not only in the phase 3 trial, but also in patients receiving DCVax-L in compassionate use. In addition, there were 70 physicians who participated in the phase 3 trial have signed as co-authors who support the JAMA Oncology paper..New York Academy of Sciences (NYAS) Conference Highlights DCVax-LThe NYAS proudly states that for over 200 years, it has brought together extraordinary people working at the frontiers of discovery. It has become an important and widely-respected contributor to the international scientific community. To drive scientific progress, the Academy hosts over 150 conferences and symposia annually, connecting experts across sectors, disciplines, and national boundaries. Research presented at the Academy is disseminated globally via in-person and virtual events, the prestigious Annals of the New York Academy of Sciences, and a broad array of digital http://media.At the May 10, 2022 meeting of the NYAS, topline data from the completed phase 3 trial of DCVax-L was selected for presentation. Promising, blinded interim data had previously been reported but this was the first time that the final topline data was presented. NYAS editors first reviewed that data and after concluding that this was an important study then asked external experts to peer review the trial. This was a rigorous process intended to establish the accuracy and credibility of the study.The study was presented by Dr. Mulholland, an investigator in the phase 3 trial. Representing the other 70 plus physicians in the trial, he stated that the trial had successfully met the primary endpoint of median overall survival in newly diagnosed glioblastoma with a highly significant p value of <0.002. It was also successful in reaching the secondary endpoint of median overall survival in recurrent GBM with a p value of <0.001. He believes that DCVax-L is a major advance in the treatment of both ndGBM and rGBM.JAMA Oncology, A Publication of the American Medical Association Publishes Peer Reviewed Article on Phase 3 StudyIn a November 17, 2022 edition of JAMA Oncology, a peer reviewed article was published that concurred with Dr. Liau, Dr. Ashkans and 70 other investigators in the study along with the NYAS that the trial had successfully reached the primary endpoint of mOS in ndGBM and secondary endpoint of mOS in rGBM. This is the most powerful validation of the results that we can hope for. I describe the internal and external experts that looked at all aspects of the clinical data and the statistical analysis used to interpret it. I describe this in detail in my recent article. See this link.Linda Liau Presents Phase 3 Results at the Society of Neuro-OncologyOn November 23, 2022, the lead investigator in the trial, Linda Liau, was invited to make a presentation at a plenary session of the Society of Neuro-Oncology in which she stated that the trial was successful. SNO is the foremost medical conference for neuro surgeons and others involved in the treatment of glioblastoma. Needless to say, this plenary presentation is another powerful endorsement of the hypothesis that DCVax-L is a significant advance in the treatment of http://glioblastoma.Now Let’s Look at F-stein.F-stein has no scientific background but boasts a degree in political science. 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 (this is especially the case for a living cell product)? Of course you would. Failing this, everything else he says is meaningless or highly questionable. On June 20, 2022 I wrote an article entitled Adam Feuerstein Investigates Adam Feuerstein’s Understanding of Dendritic Cell Vaccines. See this http://link.In searching through the plethora of articles he has written on Northwest Biotherapeutics, I was unable to find anything remotely resembling an in-depth analysis of dendritic cell vaccines or DCVax-L. 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 http://TheStreet.com. 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.After reading this linked article, I think you will concur that F-stein is utterly clueless on understanding the technology. So how does he come up with his articles? Who does he depend on? F-stein hasn’t shared his sources with us. However, he has expressed great admiration for certain hedge funds. A September 27, 2014 article was published in the Washington Post entitled Northwest Biotherapeutics stock woes highlight the harm of short sales executed by hedge funds. See this link. This article suggests a link between F-stein and short selling. I have no way of knowing if the Washington Post article is accurate and I am not alleging collusion, but this article is in the public record and investors can draw their own conclusions.Turning to Two Superficial Articles Written by Adam Feuerstein and Published by Stat NewsF-stein wrote an article on May 10, 2022 that was published in Stat News during or shortly after the NYAS presentation in which he falsely stated that the trial had failed to reach the primary endpoint which he falsely stated was progression free survival instead of median overall survival. I wrote a refutation of that article entitled Debunking Silly, Fictitious Adam Feuerstein Article Falsely Claiming Phase 3 Trial of DCVax-L in Glioblastoma Multiforme Was a Failure. Here is the link.On November 21, F-stein published a second article. This was essentially a rehash of the May 10 article so I won’t bother to refute it.
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https://www.nytimes.com/2024/07/26/business/andrew-left-short-seller-fraud.html
https://www.justice.gov/usao-cdca/media/1361671/dl?inline (doj complaint)
https://www.sec.gov/files/litigation/complaints/2024/comp-pr2024-89.pdf. (sec complaint)
Prominent Short Seller Made Millions Off Bait-and-Switch Scheme, U.S. Says
Federal authorities filed charges against Andrew Left, founder of Citron Research, who they said made at least $16 million from a multiyear scheme to manipulate market prices.
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https://www.nytimes.com/2024/07/26/business/andrew-left-short-seller-fraud.html
https://www.justice.gov/usao-cdca/media/1361671/dl?inline (doj complaint)
https://www.sec.gov/files/litigation/complaints/2024/comp-pr2024-89.pdf. (sec complaint)
Prominent Short Seller Made Millions Off Bait-and-Switch Scheme, U.S. Says
Federal authorities filed charges against Andrew Left, founder of Citron Research, who they said made at least $16 million from a multiyear scheme to manipulate market prices.
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Andrew Left leaning against a wall, with one hand in his pants pocket.
Andrew Left, founder of Citron Research, could be sentenced to 25 years or more in a federal prison if convicted.Credit...James Jackman/Bloomberg
Matthew Goldstein
By Matthew Goldstein
July 26, 2024
Updated 2:11 p.m. ET
Federal prosecutors and securities regulators filed criminal and civil fraud charges against a well-known investor who frequently appeared on cable TV business shows to discuss his often bearish views on stocks, the authorities said on Friday.
They accused the investor, Andrew Left, of raking in at least $16 million in illegal profits from a multiyear scheme to manipulate market prices of roughly two dozen stocks on which his firm, Citron Research, had published reports. He is charged with illegally profiting through stock trades he made that were contrary to the public recommendations he was making to investors.
The authorities in Los Angeles said Mr. Left essentially used a bait-and-switch strategy that was at odds with his Wall Street reputation of being a vocal short seller, with supposedly long-held negative views of the stocks on which he published critical reports.
The charging documents said Mr. Left, 54, used his high profile on Wall Street to make quick profits from big price changes in a stock and misled investors by making them believe his economic interests were aligned with what he said in his reports.
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Short sellers seek to profit from the decline in a stock’s price. Many prefer to not be so public with their views. But Mr. Left was one of the first of a new breed of short sellers to aggressively promote his bearish opinions. A 2017 profile on Mr. Left in The New York Times Magazine compared him to a journalist smoking out corporate fraud.
Mr. Left was one of the short sellers who lost money in the 2021 battle with individual investors who helped drive up the share price of GameStop and created the meme stock craze of buying stocks like mad regardless of their financial fundamentals.
The authorities said Mr. Left would give the public a false impression, through his research reports, social media and TV appearances, that he had long-term negative positions on a stock when he was really seeking to quickly profit from a sharp decline in it. They also accused him of sometimes quickly selling a stock after publishing a positive report on it.
James Spertus, a lawyer for Mr. Left, said the charges against his client “threaten the integrity of the securities markets” because federal authorities are not claiming that Mr. Left published false information about any stocks.
“The fact that Mr. Left trades in the securities he researches and writes about is well known to everyone, and there is no rule or law requiring a publisher who discloses that he is trading to also publish his private trading intentions.”
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Kate Zoladz, director of the Securities and Exchange Commission’s regional office in Los Angeles, said in a news release that Mr. Left took advantage of the trust that his followers on Wall Street had in him and would encourage them to “trade on false pretenses so that he could quickly reverse direction and profit from the price moves following his reports.”
The criminal and civil charges against Mr. Left stem from a more than two-year investigation that had taken a broad look at other so-called activist short sellers — investors who publish critical research reports on stocks.
Federal prosecutors in Los Angeles did not file charges against any other short sellers.
But in the indictment filed against Mr. Left, the authorities said he had provided some hedge funds with advance notice of his reports so those firms could make trades in anticipation of a stock’s moving on the release of a report. The indictment said Mr. Left was provided compensation by at least one hedge fund.
The authorities said Mr. Left misled investors by stating his reports were the results of his own independent research and were not shared with any other investors before publication.
The indictment did not identify any hedge funds that might have coordinated their efforts with Mr. Left. But in the S.E.C.’s civil complaint, regulators said Mr. Left had received compensation from Anson Funds, a Dallas-based hedge fund, in connection with critical reports on two stocks.
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In June, the S.E.C. reached a civil settlement with Anson over charges that it had made misleading disclosures about its work with unnamed activist short-selling firms. A representative for Anson declined to comment.
Mr. Left, whose firm was based in Beverly Hills, Calif., but who now lives in Boca Raton, Fla., is expected to be arraigned on the criminal charges in the next few weeks, said a spokesman for Martin Estrada, the U.S. attorney for the Central District of California in Los Angeles.
In all, Mr. Left is charged with 17 counts of securities fraud and one count of making false statements to federal investigators. If convicted, he could be sentenced to 25 years or more in a federal prison.
This is not the first time Mr. Left has run afoul of the authorities. In 2015, he was barred from trading in Hong Kong after securities regulators there took issue with one of Citron’s reports.
Matthew Goldstein covers Wall Street and white-collar crime and housing issues. More about Matthew Goldstein
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Regulators are looking into whether short sellers improperly influenced stock prices.
Prominent short sellers including Carson Block and Andrew Left are said to have received search warrants as part of an ongoing investigation into possible manipulation of stock prices.
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Carson Block, the founder of Muddy Waters Research, was the subject of a search warrant.Credit...Brendan Mcdermid/Reuters
Matthew GoldsteinEmily Flitter
By Matthew Goldstein and Emily Flitter
Feb. 16, 2022
Some Wall Street investors have made a profession out of exposing companies with shoddy or even fraudulent operations while betting that their share prices will fall. But Justice Department officials have been looking into whether some of these activist investors, known as short sellers, may be taking their tactics too far.
Prominent short sellers including Carson Block and Andrew Left have received search warrants as part of an ongoing investigation into possible manipulation of stock prices, according to two people familiar with the investigation. Details of the investigation were reported earlier by Bloomberg News and The Wall Street Journal.
Mr. Block, the founder of Muddy Waters Research, was served with a search warrant in the fall, according to one person familiar with the investigation. A second person familiar with the investigation said Mr. Left, who runs Citron Research, also had records seized under a search warrant early last year. The people spoke on the condition of anonymity because the details of the investigation were not public.
Subpoenas issued to several investors as part of the inquiry have asked about the sharing of information between activists betting against companies, according to two people familiar with the matter.
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Subpoenas can be routine requests for information, but search warrants are a sign of a deeper inquiry. They are more specific and frequently involve the seizure of documents and equipment.
Mr. Left declined to comment on Wednesday. He told Bloomberg this month that he was cooperating and had “full faith in the system.” Lawyers for Mr. Block’s firm had no immediate comment.
A spokesman for the U.S. attorney’s office in Los Angeles, which is leading the investigation, declined to comment. A Securities and Exchange Commission spokesman also declined to comment.
Short selling involves betting that a company’s share price will fall: Investors borrow shares of a company and sell them with the plan to repurchase shares later at a lower price and return them to the lender. Then they pocket the difference.
It is a fairly common practice on Wall Street, and some short sellers will also publish research critical of a company’s operations as part of their bets. Reports distributed by short sellers have prompted regulators to look into companies including the electric-vehicle manufacturers Nikola and Lordstown Motors and the sports betting site DraftKings. William A. Ackman, the billionaire behind Pershing Square Capital Management, famously squared off against two other billionaires — Daniel S. Loeb and Carl C. Icahn — over the dietary supplement maker Herbalife a decade ago.
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But short selling can also be risky. Last year, investors who had bet against shares of the video-game retailer GameStop were caught in a so-called short squeeze when a large number of retail investors bought shares of the company, pushing up its stock price. The squeeze left short sellers with heavy losses; one hedge fund, Melvin Capital, needed a $2 billion infusion from investors after its bet imploded.
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NEED COMPLAINT: Activist Short Seller Charged for $16M Stock Market Manipulation Scheme
Friday, July 26, 2024
Shareright caret
For Immediate Release
Office of Public Affairs
A federal grand jury in the Central District of California returned an indictment yesterday charging a prominent activist short seller with multiple counts of securities fraud for a long-running market manipulation scheme reaping profits of at least $16 million.
According to the indictment, Andrew Left, 54, formerly of Beverly Hills, California, and now a resident of Boca Raton, Florida, was a securities analyst, trader, and frequent guest commentator on cable news channels such as CNBC, Fox Business, and Bloomberg Television. Left conducted business under the name “Citron Research” (Citron), an online moniker he created as a vehicle for publishing investment recommendations. Citron’s online presence included a website and a social media account on X, formerly known as Twitter.
As alleged in the indictment, Left commented on publicly traded companies, asserting that the market incorrectly valued a company’s stock and advocating that the current price was too high or too low. Left’s recommendations often included an explicit or implicit representation about Citron’s trading position—which created the false pretense that Left’s economic incentives aligned with his public recommendation—and a “target price,” which Left represented as his valuation of the company’s stock. Sometimes, the commentary represented Left’s own work. Other times, Left disseminated the commentary of third parties as his own. The commentary routinely included sensationalized headlines and exaggerated language to maximize the reaction it would get from the stock market. As alleged, Left knowingly exploited his ability to move stock prices by targeting stocks popular with retail investors and posting recommendations on social media to manipulate the market and make fast, easy money.
As further alleged in the indictment, in the leadup to publication of Citron’s commentary, Left established long or short positions in the public company on which he was commenting in his trading accounts and prepared to quickly close those positions post-publication and take profits on the short-term price movement caused by his commentary. Left allegedly used his advance knowledge and control over the timing of a market-moving event to build his positions using inexpensive, short-dated options contracts that expired from the same day that he published his commentary to within five days. Left also allegedly submitted limit orders, often prior to publication of his commentary, to close his positions as soon as the company’s shares reached a certain price and at prices vastly different from the target prices that Left recommended to the public. While Left made false representations to the public to bolster his credibility, behind the scenes, Left allegedly took contrary trading positions to reap quick profits off the stocks he either promoted or pilloried through Citron.
To further the scheme, Left allegedly advanced the false pretense that his investment recommendations were credible because he was independent and free from any financial conflicts of interest. However, Left allegedly concealed Citron’s financial relationships with a hedge fund by fabricating invoices, wiring payments through a third party, and making false and misleading statements to the public about Citron’s relationship with hedge funds. In addition, Left allegedly lied to law enforcement, stating that Citron “never” exchanged compensation with a hedge fund or coordinated trading with a hedge fund in advance of the issuance of its commentary.
Through his publishing of research reports, Left gained influence and a public platform on social media and through regular appearances on podcasts and cable news programs. Left allegedly furthered his scheme by misrepresenting his trading positions during media appearances. For example, after denouncing one company as a “fraud” on CNBC’s “Fast Money,” Left allegedly falsely claimed to have covered only a “small size” of his position in the company’s stock when, earlier that same day, he allegedly closed out more than sixty percent of his position.
Left is charged with one count of engaging in a securities fraud scheme, 17 counts of securities fraud, and one count of making false statements to federal investigators. If convicted, he faces a maximum penalty of 25 years in prison on the securities fraud scheme count, 20 years in prison on each securities fraud count, and five years in prison on the false statements count.
Principal Deputy Assistant Attorney General Nicole M. Argentieri, head of the Justice Department’s Criminal Division; U.S. Attorney Martin Estrada for the Central District of California; Executive Assistant Director Michael A. Nordwall of the FBI’s Criminal, Cyber, Response, and Services Branch; Assistant Director in Charge Akil Davis of the FBI Los Angeles Field Office; and Inspector in Charge Eric Shen of the U.S. Postal Inspection Service (USPIS) Criminal Investigations Group made the announcement.
The FBI Los Angeles Field Office and USPIS are investigating the case.
Trial Attorneys Lauren Archer and Matthew Reilly of the Criminal Division’s Fraud Section and Assistant U.S. Attorneys Brett Sagel and Alexander Schwab for the Central District of California are prosecuting the case.
The Fraud Section uses the Victim Notification System (VNS) to provide victims with case information and updates related to this case. Victims with questions may contact the Fraud Section’s Victim Assistance Unit by calling the Victim Assistance phone line at 1-888-549-3945 or by emailing victimassistance.fraud@usdoj.gov. To learn more about victims’ rights, please visit www.justice.gov/criminal-vns/victim-rights-derechos-de-las-v-ctimas.
An indictment is merely an allegation. All defendants are presumed innocent until proven guilty beyond a reasonable doubt in a court of law.
Single Stock: we need names,addresses, emails, and cell numbers for he social media fudsters that Citron used to see if they match the fudsters on nwbo's ihub board.
Re: None
Friday, July 26, 2024 8:09:05 AM
Post#
708399
of 708406
The SEC’s complaint alleges that Andrew Left used his Citron Research website and related social media platforms on at least 26 occasions to publicly recommend taking long or short positions in 23 companies and held out the positions as consistent with his own and Citron…
newman2021:please, what indicates this?
Re: None
Thursday, July 25, 2024 1:43:19 PM
Post#
708237
of 708405
Looks like the MTD denial news is coimg after hours today. Can't wait to see the shorts running for cover, hahaha.
beartrap12:007 postulates that the chm is irrelevant to the dc vax L maa approval process.
Re: sentiment_stocks post# 708302
Thursday, July 25, 2024 5:49:54 PM
Post#
708310
of 708403
Senti, today and tomorrow the MHRA's Committee on Human Medicine (CHM) is meeting to discuss MAAs before them. I expect they'll talk about DCVax-L, though they may not be ready to vote on approval. I don't know if their decisions need to go to the MHRA board itself. If so, their decision. if CHM makes one tomorrow, may not come until next week.
Personally, I think MHRA may not rush the DCVax-L approval until they know that Flaskworks' Eden is ready or almost ready. So, maybe next month. The CHM meets the last Thursday and Friday of every month.
Yes, thanks for reminding us all of the upcoming quarterly. I hope we see lots more detail on August 9sth....if not before.
Thanks, Senti!
Bullish
PLEASE POST ALL 3 COMPLAINTS.THANKS.
"In a parallel action, the Fraud Section of the Department of Justice and the U.S. Attorney’s Office for the Central District of California today announced charges against Left."
SEC Charges Andrew Left and Citron Capital for $20 Million Fraud Scheme
Boca Raton short seller used ‘bait-and-switch’ tactics to mislead investors
FOR IMMEDIATE RELEASE
2024-89
Washington D.C., July 26, 2024 —
The Securities and Exchange Commission today announced charges against activist short seller Andrew Left and his firm, Citron Capital LLC, for engaging in a $20 million multi-year scheme to defraud followers by publishing false and misleading statements regarding his supposed stock trading recommendations.
The SEC’s complaint alleges that Left, who resides in Boca Raton, Fl., used his Citron Research website and related social media platforms on at least 26 occasions to publicly recommend taking long or short positions in 23 companies and held out the positions as consistent with his own and Citron Capital’s positions. The complaint alleges that following Left’s recommendations, the price of the target stocks moved more than 12 percent on average. According to the SEC’s complaint, once the recommendations were issued and the stocks moved, Left and Citron Capital quickly reversed their positions to capitalize on the stock price movements. As a consequence, Left bought back stock immediately after telling his readers to sell, and he sold stock immediately after telling his readers to buy.
“Andrew Left took advantage of his readers. He built their trust and induced them to trade on false pretenses so that he could quickly reverse direction and profit from the price moves following his reports,” said Kate Zoladz, Director of the SEC’s Los Angeles Regional Office. “We uncovered these alleged bait-and-switch tactics, which netted Left and his firm $20 million in ill-gotten profits, and we intend to hold Left and his firm accountable for their actions.”
The complaint alleges that Left and Citron Capital made several false and misleading statements in connection with the scheme. For example, it alleges that defendants told the market that they would stay long on a target stock until the price hit $65 when, in fact, they immediately began selling the stock at $28. It further alleges that they falsely represented to the market that Citron Research was an independent research outlet that had never received compensation from third parties to publish information about target companies when, in fact, the defendants had entered into compensation arrangements with hedge funds.
The SEC’s complaint, filed in the United States District Court for the Central District of California, charges Left and Citron Capital with violating antifraud provisions of the federal securities laws. Among other remedies, the complaint seeks disgorgement, prejudgment interest, and civil monetary penalties against Left and Citron and conduct-based injunctions, an officer-and-director bar, and a penny stock bar against Left.
In a parallel action, the Fraud Section of the Department of Justice and the U.S. Attorney’s Office for the Central District of California today announced charges against Left.
The SEC previously settled public administrative charges against Dallas-based registered investment adviser Anson Funds Management LP and Toronto-based exempt reporting adviser Anson Advisors Inc. for conduct involving their relationship with Left and other short publishers.
The SEC reminds investors to be skeptical and never make investment decisions based solely on information from social media or other unverified platforms.
The SEC’s investigation, which is ongoing, is being conducted by Sarah Nilson and Wendy Pearson and supervised by Finola Manvelian. Carina Chambarry and Michael Barnes in the SEC's Division of Economic and Risk Analysis and Darren Boerner in the Division of Enforcement’s Market Abuse Unit provided assistance. The litigation will be led by Stephen Kam and Ruth Pinkel and supervised by Doug Miller. The SEC appreciates the assistance of the Financial Industry Regulatory Authority.
###
Last Reviewed or Updated: July 26, 2024
RESOURCES
https://reuters.com/legal/legalindustry/securities-lawsuits-premised-short-seller-reports-come-up-short-2024-05-07/
@alphavestcap
$nwbo
Last edited
8:21 AM · Jul 26, 2024
View post engagements
dstock07734
Re: beartrap12 post# 708244
Thursday, July 25, 2024 2:11:02 PM
beartrap,
You are right. The future is enormously bright.
I think I got it wrong about the DOD grant. The following trial is supported by DOD.
Dendritic Cell Vaccines Against Her2/?Her3 and Pembrolizumab for the Treatment of Brain Metastasis From Triple Negative Breast Cancer or HER2+ Breast Cancer
https://clinicaltrials.gov/study/NCT04348747
Novel Immunotherapy for Brain-Metastatic Breast Cancer
https://cdmrp.health.mil/search.aspx?LOG_NO=BC180510
Re: None
Thursday, July 25, 2024 9:19:47 AM
Post#
708126
of 708256
Excellent post by beartrap12:
dstock, this ph 2 trial you found appears to be the third Ph 2 we in-licensed from Roswell and uses their DCs, NOT our DCVax-L. Note the use of intra-tumoral administration mentioned in the NWBO PR on Roswell and also in the cllinical trial that starts 10/1/2024. DCVax-L is not administered intra-tumorally:
Here is what we now own, according to our PR:
The DC based therapies include versions with tumor antigens loaded into the DCs and versions for intra-tumoral administration without pre-loading of antigens. Phase 2 trials involving the licensed technologies for two different cancers opened for enrollment earlier this year and are currently under way, and a third Phase 2 trial for a third cancer is pending. The trials are fully funded by grant funding and are being conducted as investigator led trials. The Company does not anticipate having to provide any funding or undertake any operational role for these trials.
From the clinical trial:
Patients may also receive an autologous dendritic cells intratumorally on day 50.
Great find, dstock! Thank you for all your hard work.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174805345
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174806214
8:21 AM · Jul 25, 2024
·
188
ViewsPeter Davis
@peter_brit
With $nwbo stating at the ASM that they are "working on collaborations but are not yet ready to announce these yet" and with Linda Power's master class in acquisition and in-licencing deals to date, I am really looking forward to these announcements. Should we really be surprised ? Linda's curriculum vitae is nothing short of outstanding and when she stated "Go Big or Go Home" I for one, would not bet against her achieving this with $nwbo and DCVax® - 'the gift that keeps on giving'
Ms Linda Powers | Chief Executive Officer
Northwest Biotherapeutics Inc
See new posts
Conversation
Peter Davis
@peter_brit
#dcvax $nwbo #gbm
Excellent post by Foogie88:
THERE ENTIRE POST
Flaskworks “EDEN” _ “ISSUE FEE PAYMENT RECEIVED” – JULY 23, 2024
The Flaskworks’ news is a VERY BIG DEAL, so don’t let the muted stock reaction fool you. The stock price is being suppressed by entities that are against Northwest Bio in order to create uncertainty and doubt about any positive news, with the idea being, that the news can’t be that important if the share price hardly increased. Nothing could be further from the truth.
In a nutshell, this Flaskworks news means that when Northwest Bio receives marketing approval, they will soon after, be able to produce their DCVax product to meet very strict commercial quality standards, in large quantities, at a low cost, and they will have patent protection from all the other competition that will come along and attempt to copycat Northwest Bio’s cell therapy. The biggest takeaway is that Northwest Bio has now industrialized the production process of a cell therapy, and they will be capable of producing tens of thousands of treatments annually, and eventually ramp up to hundreds of thousands as other solid-tumor indications are approved, and demand increases.
Due to the lack of any updates about the Flaskworks’ system for over a year, the haters have recently suggested that Flaskworks’ development has stalled, and that Northwest Bio is still years away from regulatory approval for an automated manufacturing system. They say that if and when Northwest Bio does receive marketing approval from regulators this year, they will have to produce the product using the very expensive, inferior manual process, which means they will only be able to produce hundreds of treatments annually, and they may not get insurance reimbursement because it will be too expensive to produce, or they won’t be able to earn much of a profit even if they do. This PR put all those ridiculous lies to death.
Since the Flaskworks acquisition in 2020, Northwest Bio (actually Flaskworks and Advent) has in fact, been very busy developing the original Flaskworks MicroDEN system, which was designed as a bench-top device intended for clinical trial production, which has lower regulatory requirements, and turning it into a commercial system with biosensors that are capable of providing real-time feedback on culturing conditions, and the ability to adjust those conditions as needed. This is necessary for commercial production, which has much higher regulatory requirements. The prototype culturing system was first revealed during a presentation entitled, Manufacturing of DCVax-L Past, Present and Future by Dr. Marnix Bosch, Chief Technical Officer of NW Bio, at ASCO on June 4, 2022. (better pictures here )
Yesterday’s Flaskworks press release revealed that in the time period since that ASCO presentation, Northwest Bio (Flaskworks and Advent) have actually further developed that commercial system, which was capable of producing one patient’s treatment (10-12 doses) at a time, into an industrial commercial system that is capable of producing 10-12 patient’s treatments (100-120 doses) at a time. This is A VERY BIG DEAL. With this Flaskworks automated process, Northwest Bio will be able to produce tens of thousands of treatments a year. All of the current companies with CAR-T cell therapy treatments are capable of producing a single patient’s treatment at a time, and are only able to produce a few thousand treatments a year. They are currently unable to meet patient demand, with long backlogs, and rationing care, which obviously limits the revenue they can earn.
So this Flaskworks news means that when the Flaskworks automated production process is approved, Northwest Bio will have the only commercial cell therapy treatment in the world that can produce enough treatments to meet a very high patient demand, which means this company will become much more valuable because the potential available revenue just skyrocketed. What this also means is that ten times the number of treatments can be manufactured from the same cleanroom footprint of that first iteration. As I said in another post a couple years ago, I think this may be what Michael Bigger was referring to as “cleanroom disruption.”
This brings up another interesting feature that was discussed in the press release; that the updated system now incorporates another previously separate process, in addition to cell culturing. As I’ve said in other posts, the manufacturing process has three main stages; the separation of the monocytes from the other white blood cells in the leukapheresis material, the culturing of those cells, and then filling the final product into individual dosage vials and cryopreserving. This new system now combines the first two steps in one system so that it not only requires less manufacturing systems, but it also allows those steps to be enclosed in one system so that it’s not necessary to transfer the cells from one machine to another, which saves time, reduces potential contamination, saves critical cleanroom space, and cuts down on expensive manpower.
Some have have speculated or at least hoped that the automated Flaskworks production process is a part of the marketing application, and it will also be approved when the DCVax product is approved. Linda Powers threw cold water on this idea at the shareholder meeting a year ago, but because the marketing application took so long to finish, some still thought that in that extra time, the development work on the Flaskworks system might also be finished. This PR dispelled this speculation, because it said that final installation, validation, and testing of the system will still need to be accomplished before it can be approved by the regulators, and the marketing application has already been submitted.
So the question that many may be asking is: “How long until it is approved by the regulators?”
First, I think it’s important to note that some of the development work that has already been completed was, “producing finished DCVax-L products with substantially the same composition and percentage purity of dendritic cells, the same biologic profile and functional characteristics of the cells, and the same yield in number of doses as with the existing manual process.” So Advent has already demonstrated to their own satisfaction that the Flaskworks’ system can produce an equivalent product as the current approved method. Now they just have to demonstrate it to the satisfaction of the regulators. They have also already engaged a contract manufacturer to make the systems that will be installed and validated at Sawston which may take a few months to receive. Then the validation - the Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ), will take a few months. Then, a few side-by-side runs for the comparability study, and gather and assess the data, and submit the Comparability Protocol to the MHRA which could take a couple more months. The MHRA should be able to review the CP within a couple months, but possibly longer if there are still staffing issues. (the EMA has a 60-day response time for this type of filing, but I’m unsure about the MHRA) If all goes well, it may be possible to receive regulatory approval, and begin automated commercial production with Flaskworks by the end of the year.
So, in summation, ………… THIS IS A VERY BIG DEAL! MFG,……MFG………MANUFACTURING…………..!!!!!!!!!!!!!
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174804997
8:35 AM · Jul 25, 2024
·
108
Views
Discover more
Sourced from across X
Peter Davis
@peter_brit
·
1h
#dcvax $nwbo #gbm
Ms. Linda F. Powers is the Chairman and Chief Executive Officer of Northwest Biotherapeutics (NW Bio), a publicly traded, NASDAQ listed Company developing personalized immune therapies for cancer. Ms. Powers has served as Chairman since May 2007, and as CEO June 2011.
Previously, Ms. Powers served as a Managing Director of Toucan Capital Fund II, a venture capital fund focused on immune therapy and regenerative medicine companies, commencing in 2001. She also has over 15 years’ experience in corporate finance and restructurings, mergers and acquisitions joint ventures and intellectual property licensing.
Ms. Powers is a Board member of M2GEN (an affiliate of Moffitt Cancer Center), the Chinese Biopharmaceutical Association, and the Rosalind Franklin Society. She serves on the MD Stem Cell Research Commission, and was the Commission Chair for the first two years of the state’s stem cell funding program. Ms. Powers served for more than 6 years on the Board of the Trudeau Institute (a specialized research institute focused on immunology). Ms. Powers served for several years on a Steering Committee of the National Academy of Sciences, evaluating government research funding, and has been appointed to three Governors’ commissions created to determine how to build the respective states’ biotech and other high-tech industries. Ms. Powers serves on the boards of a number of private biotechnology companies.
For six years, Ms. Powers taught an annual internal course at the U.S. National Institutes of Health, for bench scientists and technology transfer personnel, on the development and commercialization of house medical products. She also taught for eight years as an adjunct professor at Georgetown Law School.
Ms. Powers holds a B.A. from Princeton University, where she graduated magna cum laude and Phi Beta Kappa. She also earned a J.D., magna cum laude, from Harvard Law School.
https://terrapinn.com/conference/emerging-disease-vaccines/speaker-linda-POWERS.stm
Flaskworks acquisition:-
Northwest Biotherapeutics Acquires Flaskworks: Breakthrough Automation Technology For Cell Therapy Products To Enable Scale-Up of Production Volumes and Reduction of Production Costs
The acquisition of Flaskworks was executed and closed on August 28, 2020. The total purchase price was approximately $4.33 million, of which $1.65 million was paid in cash at closing, up to $2.01 million will be paid in stock subject to milestone-based vesting, and $0.67 million will be paid in either cash or stock, or a combination thereof, within 120 days after the closing.
The acquisition includes both intellectual property owned by Flaskworks and a license of additional intellectual property from Northeastern University.
https://nwbio.com/northwest-biotherapeutics-acquires-flaskworks-breakthrough-automation-technology-for-cell-therapy-products-to-enable-scale-up-of-production-volumes-and-reduction-of-production-costs/
Roswell Park in-licensing:-
"The portfolio in-licensed from Roswell Park is complementary to, and builds upon, a portfolio which the Company exclusively licensed from another institution last year. Together, the two portfolios encompass more than 20 years of work by one of the foremost groups of dendritic cell experts, led by Dr. Kalinski"
"The terms of the Roswell license include standard provisions for an upfront license fee and milestones related to the first Phase 2 trial, first Phase 3 trial, first product approval and first commercial sale. If all of the milestones are met, the payments would be approximately $2.3 million. The license terms also include royalties of 4% on product sales (potentially reduced to 3% in the event of royalty stacking)"
"The portfolio in-licensed last year includes the foundational technologies and IP, and positive early-stage clinical trial results, developed by the Kalinski group over 17 years before coming to Roswell. The portfolio in-licensed now includes the further work during the last 7 years at Roswell. Taken together, the Company believes that the two portfolios comprise a whole that is greater than the sum of its parts and offer compelling synergies with the Company’s own portfolio. The Company plans to collaborate with Dr. Kalinski on the further clinical development of the combined technologies"
https://nwbio.com/northwest-biotherapeutics-announces-exclusive-in-license-of-portfolio-of-dendritic-cell-technology-and-intellectual-property/
Northwest Biotherapeutics Announces Exclusive In-License of Portfolio of Dendritic Cell Technology and Intellectual Property
https://roswellpark.org/sites/default/files/2022-12/51330-innovation-tech-quick-facts_vf4.pdf
https://x.com/hoffmann6383/status/1807137334934278619
Last edited
7:23 AM · Jul 25, 2024
Excellent post by beartrap12:
dstock, this ph 2 trial you found appears to be the third Ph 2 we in-licensed from Roswell and uses their DCs, NOT our DCVax-L. Note the use of intra-tumoral administration mentioned in the NWBO PR on Roswell and also in the cllinical trial that starts 10/1/2024. DCVax-L is not administered intra-tumorally:
Here is what we now own, according to our PR:
The DC based therapies include versions with tumor antigens loaded into the DCs and versions for intra-tumoral administration without pre-loading of antigens. Phase 2 trials involving the licensed technologies for two different cancers opened for enrollment earlier this year and are currently under way, and a third Phase 2 trial for a third cancer is pending. The trials are fully funded by grant funding and are being conducted as investigator led trials. The Company does not anticipate having to provide any funding or undertake any operational role for these trials.
From the clinical trial:
Patients may also receive an autologous dendritic cells intratumorally on day 50.
Great find, dstock! Thank you for all your hard work.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174805345
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174806214
8:21 AM · Jul 25, 2024
·
188
ViewsPeter Davis
@peter_brit
With $nwbo stating at the ASM that they are "working on collaborations but are not yet ready to announce these yet" and with Linda Power's master class in acquisition and in-licencing deals to date, I am really looking forward to these announcements. Should we really be surprised ? Linda's curriculum vitae is nothing short of outstanding and when she stated "Go Big or Go Home" I for one, would not bet against her achieving this with $nwbo and DCVax® - 'the gift that keeps on giving'
Ms Linda Powers | Chief Executive Officer
Northwest Biotherapeutics Inc
See new posts
Conversation
Peter Davis
@peter_brit
#dcvax $nwbo #gbm
Excellent post by Foogie88:
THERE ENTIRE POST
Flaskworks “EDEN” _ “ISSUE FEE PAYMENT RECEIVED” – JULY 23, 2024
The Flaskworks’ news is a VERY BIG DEAL, so don’t let the muted stock reaction fool you. The stock price is being suppressed by entities that are against Northwest Bio in order to create uncertainty and doubt about any positive news, with the idea being, that the news can’t be that important if the share price hardly increased. Nothing could be further from the truth.
In a nutshell, this Flaskworks news means that when Northwest Bio receives marketing approval, they will soon after, be able to produce their DCVax product to meet very strict commercial quality standards, in large quantities, at a low cost, and they will have patent protection from all the other competition that will come along and attempt to copycat Northwest Bio’s cell therapy. The biggest takeaway is that Northwest Bio has now industrialized the production process of a cell therapy, and they will be capable of producing tens of thousands of treatments annually, and eventually ramp up to hundreds of thousands as other solid-tumor indications are approved, and demand increases.
Due to the lack of any updates about the Flaskworks’ system for over a year, the haters have recently suggested that Flaskworks’ development has stalled, and that Northwest Bio is still years away from regulatory approval for an automated manufacturing system. They say that if and when Northwest Bio does receive marketing approval from regulators this year, they will have to produce the product using the very expensive, inferior manual process, which means they will only be able to produce hundreds of treatments annually, and they may not get insurance reimbursement because it will be too expensive to produce, or they won’t be able to earn much of a profit even if they do. This PR put all those ridiculous lies to death.
Since the Flaskworks acquisition in 2020, Northwest Bio (actually Flaskworks and Advent) has in fact, been very busy developing the original Flaskworks MicroDEN system, which was designed as a bench-top device intended for clinical trial production, which has lower regulatory requirements, and turning it into a commercial system with biosensors that are capable of providing real-time feedback on culturing conditions, and the ability to adjust those conditions as needed. This is necessary for commercial production, which has much higher regulatory requirements. The prototype culturing system was first revealed during a presentation entitled, Manufacturing of DCVax-L Past, Present and Future by Dr. Marnix Bosch, Chief Technical Officer of NW Bio, at ASCO on June 4, 2022. (better pictures here )
Yesterday’s Flaskworks press release revealed that in the time period since that ASCO presentation, Northwest Bio (Flaskworks and Advent) have actually further developed that commercial system, which was capable of producing one patient’s treatment (10-12 doses) at a time, into an industrial commercial system that is capable of producing 10-12 patient’s treatments (100-120 doses) at a time. This is A VERY BIG DEAL. With this Flaskworks automated process, Northwest Bio will be able to produce tens of thousands of treatments a year. All of the current companies with CAR-T cell therapy treatments are capable of producing a single patient’s treatment at a time, and are only able to produce a few thousand treatments a year. They are currently unable to meet patient demand, with long backlogs, and rationing care, which obviously limits the revenue they can earn.
So this Flaskworks news means that when the Flaskworks automated production process is approved, Northwest Bio will have the only commercial cell therapy treatment in the world that can produce enough treatments to meet a very high patient demand, which means this company will become much more valuable because the potential available revenue just skyrocketed. What this also means is that ten times the number of treatments can be manufactured from the same cleanroom footprint of that first iteration. As I said in another post a couple years ago, I think this may be what Michael Bigger was referring to as “cleanroom disruption.”
This brings up another interesting feature that was discussed in the press release; that the updated system now incorporates another previously separate process, in addition to cell culturing. As I’ve said in other posts, the manufacturing process has three main stages; the separation of the monocytes from the other white blood cells in the leukapheresis material, the culturing of those cells, and then filling the final product into individual dosage vials and cryopreserving. This new system now combines the first two steps in one system so that it not only requires less manufacturing systems, but it also allows those steps to be enclosed in one system so that it’s not necessary to transfer the cells from one machine to another, which saves time, reduces potential contamination, saves critical cleanroom space, and cuts down on expensive manpower.
Some have have speculated or at least hoped that the automated Flaskworks production process is a part of the marketing application, and it will also be approved when the DCVax product is approved. Linda Powers threw cold water on this idea at the shareholder meeting a year ago, but because the marketing application took so long to finish, some still thought that in that extra time, the development work on the Flaskworks system might also be finished. This PR dispelled this speculation, because it said that final installation, validation, and testing of the system will still need to be accomplished before it can be approved by the regulators, and the marketing application has already been submitted.
So the question that many may be asking is: “How long until it is approved by the regulators?”
First, I think it’s important to note that some of the development work that has already been completed was, “producing finished DCVax-L products with substantially the same composition and percentage purity of dendritic cells, the same biologic profile and functional characteristics of the cells, and the same yield in number of doses as with the existing manual process.” So Advent has already demonstrated to their own satisfaction that the Flaskworks’ system can produce an equivalent product as the current approved method. Now they just have to demonstrate it to the satisfaction of the regulators. They have also already engaged a contract manufacturer to make the systems that will be installed and validated at Sawston which may take a few months to receive. Then the validation - the Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ), will take a few months. Then, a few side-by-side runs for the comparability study, and gather and assess the data, and submit the Comparability Protocol to the MHRA which could take a couple more months. The MHRA should be able to review the CP within a couple months, but possibly longer if there are still staffing issues. (the EMA has a 60-day response time for this type of filing, but I’m unsure about the MHRA) If all goes well, it may be possible to receive regulatory approval, and begin automated commercial production with Flaskworks by the end of the year.
So, in summation, ………… THIS IS A VERY BIG DEAL! MFG,……MFG………MANUFACTURING…………..!!!!!!!!!!!!!
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174804997
8:35 AM · Jul 25, 2024
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Peter Davis
@peter_brit
·
1h
#dcvax $nwbo #gbm
Ms. Linda F. Powers is the Chairman and Chief Executive Officer of Northwest Biotherapeutics (NW Bio), a publicly traded, NASDAQ listed Company developing personalized immune therapies for cancer. Ms. Powers has served as Chairman since May 2007, and as CEO June 2011.
Previously, Ms. Powers served as a Managing Director of Toucan Capital Fund II, a venture capital fund focused on immune therapy and regenerative medicine companies, commencing in 2001. She also has over 15 years’ experience in corporate finance and restructurings, mergers and acquisitions joint ventures and intellectual property licensing.
Ms. Powers is a Board member of M2GEN (an affiliate of Moffitt Cancer Center), the Chinese Biopharmaceutical Association, and the Rosalind Franklin Society. She serves on the MD Stem Cell Research Commission, and was the Commission Chair for the first two years of the state’s stem cell funding program. Ms. Powers served for more than 6 years on the Board of the Trudeau Institute (a specialized research institute focused on immunology). Ms. Powers served for several years on a Steering Committee of the National Academy of Sciences, evaluating government research funding, and has been appointed to three Governors’ commissions created to determine how to build the respective states’ biotech and other high-tech industries. Ms. Powers serves on the boards of a number of private biotechnology companies.
For six years, Ms. Powers taught an annual internal course at the U.S. National Institutes of Health, for bench scientists and technology transfer personnel, on the development and commercialization of house medical products. She also taught for eight years as an adjunct professor at Georgetown Law School.
Ms. Powers holds a B.A. from Princeton University, where she graduated magna cum laude and Phi Beta Kappa. She also earned a J.D., magna cum laude, from Harvard Law School.
https://terrapinn.com/conference/emerging-disease-vaccines/speaker-linda-POWERS.stm
Flaskworks acquisition:-
Northwest Biotherapeutics Acquires Flaskworks: Breakthrough Automation Technology For Cell Therapy Products To Enable Scale-Up of Production Volumes and Reduction of Production Costs
The acquisition of Flaskworks was executed and closed on August 28, 2020. The total purchase price was approximately $4.33 million, of which $1.65 million was paid in cash at closing, up to $2.01 million will be paid in stock subject to milestone-based vesting, and $0.67 million will be paid in either cash or stock, or a combination thereof, within 120 days after the closing.
The acquisition includes both intellectual property owned by Flaskworks and a license of additional intellectual property from Northeastern University.
https://nwbio.com/northwest-biotherapeutics-acquires-flaskworks-breakthrough-automation-technology-for-cell-therapy-products-to-enable-scale-up-of-production-volumes-and-reduction-of-production-costs/
Roswell Park in-licensing:-
"The portfolio in-licensed from Roswell Park is complementary to, and builds upon, a portfolio which the Company exclusively licensed from another institution last year. Together, the two portfolios encompass more than 20 years of work by one of the foremost groups of dendritic cell experts, led by Dr. Kalinski"
"The terms of the Roswell license include standard provisions for an upfront license fee and milestones related to the first Phase 2 trial, first Phase 3 trial, first product approval and first commercial sale. If all of the milestones are met, the payments would be approximately $2.3 million. The license terms also include royalties of 4% on product sales (potentially reduced to 3% in the event of royalty stacking)"
"The portfolio in-licensed last year includes the foundational technologies and IP, and positive early-stage clinical trial results, developed by the Kalinski group over 17 years before coming to Roswell. The portfolio in-licensed now includes the further work during the last 7 years at Roswell. Taken together, the Company believes that the two portfolios comprise a whole that is greater than the sum of its parts and offer compelling synergies with the Company’s own portfolio. The Company plans to collaborate with Dr. Kalinski on the further clinical development of the combined technologies"
https://nwbio.com/northwest-biotherapeutics-announces-exclusive-in-license-of-portfolio-of-dendritic-cell-technology-and-intellectual-property/
Northwest Biotherapeutics Announces Exclusive In-License of Portfolio of Dendritic Cell Technology and Intellectual Property
https://roswellpark.org/sites/default/files/2022-12/51330-innovation-tech-quick-facts_vf4.pdf
https://x.com/hoffmann6383/status/1807137334934278619
Last edited
7:23 AM · Jul 25, 2024
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alphavestcapital.com
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$nwbo
@alphavestcap
Looks like Citadel, et al, are getting sued by the creditors of Glorifi(Purpose, Inc) after Glorifi's bankruptcy. Could discovery in the $nwbo - Citadel case help the plaintiffs in the Glorifi lawsuit? Please post the Glorifi plaintiffs' 140 page complaint.
https://unicourt.com/case/pc-db5-casegud39047e9a122-1838937
BANKRUPTCY TRUSTEE JOINS DEBT HOLDERS OF GLORIFI TO PURSUE ALLEGED SABOTEURS
BANKRUPTCY TRUSTEE JOINS DEBT HOLDERS OF GLORIFI TO PURSUE ALLEGED SABOTEURS
PR Newswire
DALLAS, July 22, 2024
Defendants Citadel, Peter Thiel, Vivek Ramaswamy, Joe Lonsdale, Rick Jackson, Nick Ayers and others named in the Georgia RICO suit
DALLAS, July 22, 2024 /PRNewswire/ -- With Purpose, Inc. d/b/a GloriFi today announces its Chapter 7 Bankruptcy Trustee, its secured creditors, and its former CEO, Toby Neugebauer, entered into a joint prosecution agreement, subject to court approval, to pursue defendants alleged to have conspired against the pro-America financial services challenger.
The Trustee filed a motion for court approval of the joint prosecution agreement in the company's Chapter 7 bankruptcy proceedings, following a May lawsuit filed by WPI Collateral Management, LLC on behalf of GloriFi's secured creditors in the U.S. District Court for the Northern District of Georgia. The 140-page complaint details allegations of defamation and intellectual property theft at the hands of Defendants Citadel, LLC, Peter Thiel, Vivek Ramaswamy, Joe Lonsdale, Nick Ayers, Rick Jackson, Keri Findley and other notable individuals who are accused of conspiring to gain control of GloriFi for their benefit. According to the lawsuit, the defendants launched a "blitzkrieg" campaign to make the company uninvestable for anyone but themselves, while forming and/or investing in competitive companies. The lawsuit further outlines the alleged actions that ultimately resulted in GloriFi's closure in 2022.
With a strong ethos and powerful technological capabilities, GloriFi was poised to achieve extraordinary success on par with the Nation's most successful companies. Within days of a social media post kicking off the launch, GloriFi had onboarded 33,000 members with 5,000 opening a financial services account. The suit alleges that 72 hours later the Defendants orchestrated a final fatal blow.
At the time of its closure, the unicorn company had on file with the Securities and Exchange Commission a merger agreement with DHC Acquisition Corp, a Nasdaq listed company, valuing it at $1.65 Billion.
On behalf of the company, Neugebauer said, "as this litigation process unfolds, the employee-owners welcome their day in court where each can share their story - what they achieved at GloriFi and how the Defendants who reap the greatest rewards of America allegedly destroyed the company that would give them their rightful hard-earned piece of the pie."
WPI Collateral Management, LLC is represented by Ryan Downton of the Texas Trial Group and Chris Timmons of Knowles Gallant Timmons LLC. Any former GloriFi employee or creditor seeking more information can contact Mr. Downton at Ryan@TheTexasTrialGroup.com.
MEDIA CONTACT:
Megan Paquin, APR, CPRC
Paquin Public Relations 407-432-7066
megan@paquinpr.com
$nwbo @alphavestcap @hoffmann6383 @BrianEgolf2 @SmithOnStocks1 @ATLnsider
— alphavestcapital.com (@alphavestcap) July 25, 2024
Looks like Citadel, et al, are getting sued by the creditors of Glorifi(Purpose, Inc) after Glorifi's bankruptcy. Could discovery in the $nwbo Citadel case help the plaintiffs in the Glorifi lawsuit?… https://t.co/xLl8rXCxFq
Looks like Citadel, et al, are getting sued by the creditors of Glorifi(Purpose, Inc) after Glorifi's bankruptcy. Could discovery in the $nwbo - Citadel case help the plaintiffs in the Glorifi lawsuit? Please post the Glorifi plaintiffs' 140 page complaint.
https://unicourt.com/case/pc-db5-casegud39047e9a122-1838937
BANKRUPTCY TRUSTEE JOINS DEBT HOLDERS OF GLORIFI TO PURSUE ALLEGED SABOTEURS
BANKRUPTCY TRUSTEE JOINS DEBT HOLDERS OF GLORIFI TO PURSUE ALLEGED SABOTEURS
PR Newswire
DALLAS, July 22, 2024
Defendants Citadel, Peter Thiel, Vivek Ramaswamy, Joe Lonsdale, Rick Jackson, Nick Ayers and others named in the Georgia RICO suit
DALLAS, July 22, 2024 /PRNewswire/ -- With Purpose, Inc. d/b/a GloriFi today announces its Chapter 7 Bankruptcy Trustee, its secured creditors, and its former CEO, Toby Neugebauer, entered into a joint prosecution agreement, subject to court approval, to pursue defendants alleged to have conspired against the pro-America financial services challenger.
The Trustee filed a motion for court approval of the joint prosecution agreement in the company's Chapter 7 bankruptcy proceedings, following a May lawsuit filed by WPI Collateral Management, LLC on behalf of GloriFi's secured creditors in the U.S. District Court for the Northern District of Georgia. The 140-page complaint details allegations of defamation and intellectual property theft at the hands of Defendants Citadel, LLC, Peter Thiel, Vivek Ramaswamy, Joe Lonsdale, Nick Ayers, Rick Jackson, Keri Findley and other notable individuals who are accused of conspiring to gain control of GloriFi for their benefit. According to the lawsuit, the defendants launched a "blitzkrieg" campaign to make the company uninvestable for anyone but themselves, while forming and/or investing in competitive companies. The lawsuit further outlines the alleged actions that ultimately resulted in GloriFi's closure in 2022.
With a strong ethos and powerful technological capabilities, GloriFi was poised to achieve extraordinary success on par with the Nation's most successful companies. Within days of a social media post kicking off the launch, GloriFi had onboarded 33,000 members with 5,000 opening a financial services account. The suit alleges that 72 hours later the Defendants orchestrated a final fatal blow.
At the time of its closure, the unicorn company had on file with the Securities and Exchange Commission a merger agreement with DHC Acquisition Corp, a Nasdaq listed company, valuing it at $1.65 Billion.
On behalf of the company, Neugebauer said, "as this litigation process unfolds, the employee-owners welcome their day in court where each can share their story - what they achieved at GloriFi and how the Defendants who reap the greatest rewards of America allegedly destroyed the company that would give them their rightful hard-earned piece of the pie."
WPI Collateral Management, LLC is represented by Ryan Downton of the Texas Trial Group and Chris Timmons of Knowles Gallant Timmons LLC. Any former GloriFi employee or creditor seeking more information can contact Mr. Downton at Ryan@TheTexasTrialGroup.com.
MEDIA CONTACT:
Megan Paquin, APR, CPRC
Paquin Public Relations 407-432-7066
megan@paquinpr.com
$nwbo @alphavestcap @hoffmann6383 @BrianEgolf2 @SmithOnStocks1 @ATLnsider
— alphavestcapital.com (@alphavestcap) July 25, 2024
Looks like Citadel, et al, are getting sued by the creditors of Glorifi(Purpose, Inc) after Glorifi's bankruptcy. Could discovery in the $nwbo Citadel case help the plaintiffs in the Glorifi lawsuit?… https://t.co/xLl8rXCxFq
dstock07734 : These two trials and the phase 3 were bought for $2.5 million, I assume.
After the PR, my buddy said, " Each of those 2 trials could be worth $1 billion someday.". Then it dawned on me that maybe the price of $ nwbo is set by Citadel and other 6 market makers, and no one else.
https://nwbio.com/northwest-biotherapeutics-announces-exclusive-in-license-of-portfolio-of-dendritic-cell-technology-and-intellectual-property/
Re: None
Wednesday, July 24, 2024 9:38:54 PM
Post#
708069
of 708074
Pembrolizumab and Autologous Dendritic Cells for the Treatment of Refractory Colorectal Cancer (CRC)
https://clinicaltrials.gov/study/NCT05518032
Dendritic Cell-Based Treatment Plus Immunotherapy for the Treatment of Metastatic or Unresectable Triple Negative Breast Cancer
https://clinicaltrials.gov/study/NCT05539365
About
Professor Ashkan is a leading neurosurgeon at King’s College Hospital, London and one of the handful of neurosurgeons in the UK to be awarded a Professorship. Professor Ashkan underwent dual postgraduate training in medicine and surgery, obtaining Membership of the Royal College of Physicians in 1997 and the Fellowship of the Royal Colleges of Surgeons of England and Glasgow (FRCS) in 1998. Thereafter, he underwent higher specialist training in general neurosurgery in London, being awarded the Fellowship of the Royal College of Surgeons in Neurosurgery (FRCS SN) in 2002. His subspecialist training in stereotactic and functional neurosurgery included a Fellowship in France with Professor Benabid, generally considered as the founder of modern deep brain stimulation surgery, which led to a MD degree in 2006. He was appointed as a Consultant Neurosurgeon at King’s College Hospital in January 2007 and subsequently was promoted to the position of Professor.
In addition to his expertise in degenerative spine disease, which includes the management of back and neck pain, arm pain and sciatica together with peripheral nerve disorders such as carpal tunnel syndrome, Professor Ashkan’s main interests are neuromodulation surgery and brain tumours. This includes deep brain stimulation, spinal cord stimulation and occipital nerve stimulation for movement disorders, pain, headaches and image guided minimally invasive and stereotactic surgery for brain tumours including awake craniotomies and brain mapping. He is also one of the few UK surgeons trained in Gamma and Cyberknife radiosurgery.
He is the UK Lead for Genomics England programme for brain tumour, President of the British Society for Stereotactic and Functional Neurosurgery, Chairman of the Neurosurgery Section of the International Parkinson and Movement Disorder Society, King’s Lead for Neuro-Oncology, Chair of King’s Neuroscience Clinical Trial Unit and Deputy Lead for King’s Neuroscience Research Advisory Committee.
Professor Ashkan has published over 400 peer review papers, abstracts and book chapters and is an Associate Editor or reviewer for several journals.
In his spare time Professor Ashkan has completed a degree and diploma in music and enjoys playing the piano.
Diseases, Medical Tests and Treatments
Visualase, Deep Brain Stimulation, Spinal Cord Stimulation, Occipital Nerve Stimulation, DCVax Immunotherapy, Awake Craniotomy, Surgery for Brain Tumours, Visualase, Gamma-knife and Cyberknife Radiosurgery, Lumbar and Cervical Laminectomy and Discectomy.
Parkinson's disease, Essential Tremor, Brain Tumours, Spine Disease, Back Pain, Sciatica.
SUBSPECIALITIES
Functional Neurosurgery
ALL PROCEDURES
Brain Surgery
Discectomy
Laminectomy
Spinal Decompression
Awake Craniotomy
Gamma Knife Radiosurgery
Laser Ablation Brain Surgery
Lumbar Back Surgery
Sciatica Surgery
Scoliosis Surgery
Spine Fracture Surgery
Video Consultation
ALL CONDITIONS
Brain Tumours
Herniated Disc or Slipped Disc
Metastases
Carpal Tunnel Syndrome
Degenerative Disc Disease
Hydrocephalus
Sciatica
Scoliosis
Spinal Stenosis
Spine Fractures and Trauma
Spondylolisthesis & Spondylosis
Sports-Related Spine Injuries
LANGUAGES
English, Farsi
QUALIFICATIONS
BA BSc MB BCh FRCP FRCPath FRCS FRCPS FRCS (SN) MD
REGISTERED WITH
General Medical Council: 4011040
Locations
The Harley Street Clinic, part of HCA Healthcare UK
35 Weymouth Street, London, W1G 8BJ
Wednesday, July 24, 2024 6:52:13 AM
@InvestorTurf
Predatory institution Citadel LLC, named in the Georgia RICO suit, face allegations of defamation and intellectual property theft detailed in a 140-page complaint. Citadel LLC and other prominent individuals are accused of conspiring to gain control of GloriFi for their own benefit.
According to the lawsuit, the defendants launched a "blitzkrieg" campaign to render the company uninvestable for anyone but themselves while forming and investing in competitive companies. The lawsuit further outlines the alleged actions that ultimately led to GloriFi's closure in 2022.
BANKRUPTCY TRUSTEE JOINS DEBT HOLDERS OF GLORIFI TO PURSUE ALLEGED SABOTEURS
NEWS PROVIDED BY
Glorifi
Jul 22, 2024, 15:18 ET
SHARE THIS ARTICLE
Defendants Citadel, Peter Thiel, Vivek Ramaswamy, Joe Lonsdale, Rick Jackson, Nick Ayers and others named in the Georgia RICO suit
DALLAS, July 22, 2024 /PRNewswire/ -- With Purpose, Inc. d/b/a GloriFi today announces its Chapter 7 Bankruptcy Trustee, its secured creditors, and its former CEO, Toby Neugebauer, entered into a joint prosecution agreement, subject to court approval, to pursue defendants alleged to have conspired against the pro-America financial services challenger.
The Trustee filed a motion for court approval of the joint prosecution agreement in the company's Chapter 7 bankruptcy proceedings, following a May lawsuit filed by WPI Collateral Management, LLC on behalf of GloriFi's secured creditors in the U.S. District Court for the Northern District of Georgia. The 140-page complaint details allegations of defamation and intellectual property theft at the hands of Defendants Citadel, LLC, Peter Thiel, Vivek Ramaswamy, Joe Lonsdale, Nick Ayers, Rick Jackson, Keri Findley and other notable individuals who are accused of conspiring to gain control of GloriFi for their benefit. According to the lawsuit, the defendants launched a "blitzkrieg" campaign to make the company uninvestable for anyone but themselves, while forming and/or investing in competitive companies. The lawsuit further outlines the alleged actions that ultimately resulted in GloriFi's closure in 2022.
With a strong ethos and powerful technological capabilities, GloriFi was poised to achieve extraordinary success on par with the Nation's most successful companies. Within days of a social media post kicking off the launch, GloriFi had onboarded 33,000 members with 5,000 opening a financial services account. The suit alleges that 72 hours later the Defendants orchestrated a final fatal blow.
At the time of its closure, the unicorn company had on file with the Securities and Exchange Commission a merger agreement with DHC Acquisition Corp, a Nasdaq listed company, valuing it at $1.65 Billion.
On behalf of the company, Neugebauer said, "as this litigation process unfolds, the employee-owners welcome their day in court where each can share their story - what they achieved at GloriFi and how the Defendants who reap the greatest rewards of America allegedly destroyed the company that would give them their rightful hard-earned piece of the pie."
WPI Collateral Management, LLC is represented by Ryan Downton of the Texas Trial Group and Chris Timmons of Knowles Gallant Timmons LLC. Any former GloriFi employee or creditor seeking more information can contact Mr. Downton at Ryan@TheTexasTrialGroup.com.
MEDIA CONTACT:
Megan Paquin, APR, CPRC
Paquin Public Relations 407-432-7066
megan@paquinpr.com
Foogie88
Re: None
Wednesday, July 24, 2024 7:51:44 PM
Post#
708061
of 708067
THERE ENTIRE POST
Flaskworks “EDEN” _ “ISSUE FEE PAYMENT RECEIVED” – JULY 23, 2024
The Flaskworks’ news is a VERY BIG DEAL, so don’t let the muted stock reaction fool you. The stock price is being suppressed by entities that are against Northwest Bio in order to create uncertainty and doubt about any positive news, with the idea being, that the news can’t be that important if the share price hardly increased. Nothing could be further from the truth.
In a nutshell, this Flaskworks news means that when Northwest Bio receives marketing approval, they will soon after, be able to produce their DCVax product to meet very strict commercial quality standards, in large quantities, at a low cost, and they will have patent protection from all the other competition that will come along and attempt to copycat Northwest Bio’s cell therapy. The biggest takeaway is that Northwest Bio has now industrialized the production process of a cell therapy, and they will be capable of producing tens of thousands of treatments annually, and eventually ramp up to hundreds of thousands as other solid-tumor indications are approved, and demand increases.
Due to the lack of any updates about the Flaskworks’ system for over a year, the haters have recently suggested that Flaskworks’ development has stalled, and that Northwest Bio is still years away from regulatory approval for an automated manufacturing system. They say that if and when Northwest Bio does receive marketing approval from regulators this year, they will have to produce the product using the very expensive, inferior manual process, which means they will only be able to produce hundreds of treatments annually, and they may not get insurance reimbursement because it will be too expensive to produce, or they won’t be able to earn much of a profit even if they do. This PR put all those ridiculous lies to death.
Since the Flaskworks acquisition in 2020, Northwest Bio (actually Flaskworks and Advent) has in fact, been very busy developing the original Flaskworks MicroDEN system, which was designed as a bench-top device intended for clinical trial production, which has lower regulatory requirements, and turning it into a commercial system with biosensors that are capable of providing real-time feedback on culturing conditions, and the ability to adjust those conditions as needed. This is necessary for commercial production, which has much higher regulatory requirements. The prototype culturing system was first revealed during a presentation entitled, Manufacturing of DCVax-L Past, Present and Future by Dr. Marnix Bosch, Chief Technical Officer of NW Bio, at ASCO on June 4, 2022. (better pictures here )
Yesterday’s Flaskworks press release revealed that in the time period since that ASCO presentation, Northwest Bio (Flaskworks and Advent) have actually further developed that commercial system, which was capable of producing one patient’s treatment (10-12 doses) at a time, into an industrial commercial system that is capable of producing 10-12 patient’s treatments (100-120 doses) at a time. This is A VERY BIG DEAL. With this Flaskworks automated process, Northwest Bio will be able to produce tens of thousands of treatments a year. All of the current companies with CAR-T cell therapy treatments are capable of producing a single patient’s treatment at a time, and are only able to produce a few thousand treatments a year. They are currently unable to meet patient demand, with long backlogs, and rationing care, which obviously limits the revenue they can earn.
So this Flaskworks news means that when the Flaskworks automated production process is approved, Northwest Bio will have the only commercial cell therapy treatment in the world that can produce enough treatments to meet a very high patient demand, which means this company will become much more valuable because the potential available revenue just skyrocketed. What this also means is that ten times the number of treatments can be manufactured from the same cleanroom footprint of that first iteration. As I said in another post a couple years ago, I think this may be what Michael Bigger was referring to as “cleanroom disruption.”
This brings up another interesting feature that was discussed in the press release; that the updated system now incorporates another previously separate process, in addition to cell culturing. As I’ve said in other posts, the manufacturing process has three main stages; the separation of the monocytes from the other white blood cells in the leukapheresis material, the culturing of those cells, and then filling the final product into individual dosage vials and cryopreserving. This new system now combines the first two steps in one system so that it not only requires less manufacturing systems, but it also allows those steps to be enclosed in one system so that it’s not necessary to transfer the cells from one machine to another, which saves time, reduces potential contamination, saves critical cleanroom space, and cuts down on expensive manpower.
Some have have speculated or at least hoped that the automated Flaskworks production process is a part of the marketing application, and it will also be approved when the DCVax product is approved. Linda Powers threw cold water on this idea at the shareholder meeting a year ago, but because the marketing application took so long to finish, some still thought that in that extra time, the development work on the Flaskworks system might also be finished. This PR dispelled this speculation, because it said that final installation, validation, and testing of the system will still need to be accomplished before it can be approved by the regulators, and the marketing application has already been submitted.
So the question that many may be asking is: “How long until it is approved by the regulators?”
First, I think it’s important to note that some of the development work that has already been completed was, “producing finished DCVax-L products with substantially the same composition and percentage purity of dendritic cells, the same biologic profile and functional characteristics of the cells, and the same yield in number of doses as with the existing manual process.” So Advent has already demonstrated to their own satisfaction that the Flaskworks’ system can produce an equivalent product as the current approved method. Now they just have to demonstrate it to the satisfaction of the regulators. They have also already engaged a contract manufacturer to make the systems that will be installed and validated at Sawston which may take a few months to receive. Then the validation - the Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ), will take a few months. Then, a few side-by-side runs for the comparability study, and gather and assess the data, and submit the Comparability Protocol to the MHRA which could take a couple more months. The MHRA should be able to review the CP within a couple months, but possibly longer if there are still staffing issues. (the EMA has a 60-day response time for this type of filing, but I’m unsure about the MHRA) If all goes well, it may be possible to receive regulatory approval, and begin automated commercial production with Flaskworks by the end of the year.
So, in summation, ………… THIS IS A VERY BIG DEAL! MFG,……MFG………MANUFACTURING…………..!!!!!!!!!!!!!
eagle8:please post the complaint. thanks.
Wednesday, July 24, 2024 6:52:13 AM
@InvestorTurf
Predatory institution Citadel LLC, named in the Georgia RICO suit, face allegations of defamation and intellectual property theft detailed in a 140-page complaint. Citadel LLC and other prominent individuals are accused of conspiring to gain control of GloriFi for their own benefit.
According to the lawsuit, the defendants launched a "blitzkrieg" campaign to render the company uninvestable for anyone but themselves while forming and investing in competitive companies. The lawsuit further outlines the alleged actions that ultimately led to GloriFi's closure in 2022.
Excellent post by
@d_stock07734
A hypothetical question:
Assuming the collaboration trial between Merck and NWBO is real, can Merck file for FDA approval for the combination on colorectal cancer?
A multi-center, Phase II clinical trial evaluating DCVax-L (autologous dendritic cells pulsed with tumor lysate antigen) and pembrolizumab (an anti–PD-1 monoclonal antibody) for subjects with liver metastases of primary colorectal carcinoma
https://rlp-forschung.de/public/facilities/2807/research_projects/22146
Merck filed for FDA approval of an ADC based on a phase 2 trial which was solely run by Daiichi Sankyo. But Merck did sign a deal with Daiichi about this specific ADC last October. That's why I was wondering whether Merck can for FDA approval based on the results from the collaboration trial.
Patritumab Deruxtecan BLA Submission Receives Complete Response Letter from FDA Due to Inspection Findings at Third-Party Manufacturer
https://merck.com/news/patritumab-deruxtecan-bla-submission-receives-complete-response-letter-from-fda-due-to-inspection-findings-at-third-party-manufacturer/
HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer
https://clinicaltrials.gov/study/NCT04619004
https://daiichisankyo.us/press-releases/-/article/patritumab-deruxtecan-demonstrated-clinically-meaningful-and-durable-responses-in-patients-with-egfr-mutated-metastatic-non-small-cell-lung-cancer-in-
https://merck.com/news/daiichi-sankyo-and-merck-announce-global-development-and-commercialization-collaboration-for-three-daiichi-sankyo-dxd-adcs/
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174796910
7/24
dstock07734
Re: None
Tuesday, July 23, 2024 2:43:30 PM
Post#
707777
of 707875
This project with Dr. Robert Prins as the PI is up for renewal the end of this month. The research has been going on for over five years. Will UCLA start running a clinical trial using the technology licensed from NWBO in the coming new budget year?
Project 1: Targeting immunotherapy-induced resistance with DC vaccination and PD-1/CSF-1R inhibition
https://reporter.nih.gov/search/aoyfNLfFVUq2O5ILmmPMMQ/project-details/10673749
Abstract Text
PROJECT SUMMARY/ABSTRACT – Project 1 The lack of effective treatments for glioblastoma (GBM) patients remains a significant health problem and highlights the need for novel and innovative approaches. Immunotherapy is an appealing strategy because of the potential ability for immune cells to traffic to and destroy infiltrating tumor cells in the brain. For the past 15 years, our group and others have been testing active vaccination strategies, such as dendritic cells (DC) pulsed with tumor lysate, to induce antitumor immunity in glioblastoma patients. From the interim results of the clinical trial we initiated in our current SPORE funding period, we found that in addition to inducing T-cell infiltration into brain tumors, DC vaccination + anti-PD1 blockade may also create a pro-inflammatory environment within the tumor that induces the immigration of immunosuppressive myeloid cells (TIM). These cells are phenotypically similar to the myeloid cells that dominantly attenuate the T-cell response to chronic viral infections, and may counteract the effective anti-tumor T-cell responses induced by DC vaccination within the tumor microenvironment. Therapies that target myeloid cells within the tumor microenvironment represent a promising new strategy. As such, inhibition of these myeloid cells using a CSF-1R inhibitor, in conjunction with autologous tumor lysate-pulsed DC vaccination (ATL-DC) and PD-1 mAb blockade, resulted in significantly prolonged survival in tumor-bearing animals with large, well-established intracranial (i.c.) gliomas. Our hypothesis is that myeloid cells mediate adaptive immune resistance in response to T cell activation induced by immunotherapy. In this SPORE Project renewal, we have planned a series of novel pre-clinical studies to re- polarize myeloid cells, to optimize how the timing and sequence of immunotherapy can influence ant-tumor immunity, and a new clinical trial to test the first-in-human combination of a new brain penetrant CSF-1R inhibitor (CSF-1Ri; PLX3397, Daiichi-Sankyo) with DC vaccination and PD-1 mAb blockade (Pembrolizumab, Merck) in patients with newly diagnosed GBM. A better understanding of the biology of these cellular interactions will provide insight into more effective ways to induce therapeutic anti-tumor immune responses for this deadly type of brain tumor. These studies span the continuum of translational research in brain tumor immunotherapy, and will likely provided informative new insights for the development of new, rational immune-based strategies for brain tumor patients.Re: dstock07734 post# 707805
Tuesday, July 23, 2024 6:10:16 PM
Post#
707843
of 707875
“Leidos
https://www.highergov.com/idv/75N95022D00022/
Battelle Memorial Institute
https://www.highergov.com/idv/75N95022D00021/
Battelle, AmplifyBio, Andelyn Biosciences Win Research Contract for National Institute of Neurological Disorders and Stroke
https://www.battelle.org/insights/newsroom/press-release-details/battelle-amplifybio-andelyn-biosciences-win-research-contract-for-national-institute-of-neurological-disorders-and-stroke “
Interesting note: Louis Von Thaer, President & CEO of Battelle, joined Battelle in 2017 and had been a senior executive with Leidos; currently he is Chairman of the Board of AmplifyBio.
Re: None
Tuesday, July 23, 2024 2:17:59 PM
Post#
707758
of 707875
A hypothetical question:
Assuming the collaboration trial between Merck and NWBO is real, can Merck file for FDA approval for the combination on colorectal cancer?
A multi-center, Phase II clinical trial evaluating DCVax-L (autologous dendritic cells pulsed with tumor lysate antigen) and pembrolizumab (an anti–PD-1 monoclonal antibody) for subjects with liver metastases of primary colorectal carcinoma
https://www.rlp-forschung.de/public/facilities/2807/research_projects/22146
Merck filed for FDA approval of an ADC based on a phase 2 trial which was solely run by Daiichi Sankyo. But Merck did sign a deal with Daiichi about this specific ADC last October. That's why I was wondering whether Merck can for FDA approval based on the results from the collaboration trial.
Patritumab Deruxtecan BLA Submission Receives Complete Response Letter from FDA Due to Inspection Findings at Third-Party Manufacturer
https://www.merck.com/news/patritumab-deruxtecan-bla-submission-receives-complete-response-letter-from-fda-due-to-inspection-findings-at-third-party-manufacturer/
HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer
https://clinicaltrials.gov/study/NCT04619004
https://daiichisankyo.us/press-releases/-/article/patritumab-deruxtecan-demonstrated-clinically-meaningful-and-durable-responses-in-patients-with-egfr-mutated-metastatic-non-small-cell-lung-cancer-in-
https://www.merck.com/news/daiichi-sankyo-and-merck-announce-global-development-and-commercialization-collaboration-for-three-daiichi-sankyo-dxd-adcs/
Re: manibiotech post# 707761
Tuesday, July 23, 2024 2:30:58 PM
Post#
707764
of 707875
Poly-iclc must be bonded with DCVax-L to have efficacy. I simply cannot see how poly-iclc alone without any efficacy data from all the previous clinical trials can convince all the RAs all over the world to grant the approval.
https://gritdaily.com/cancer-therapy-oncovirs-hiltonol/
“We have a drug master file with the FDA, and we have been in front of many of the world’s tier 1 regulatory agencies including the European Union Countries including France and Switzerland, in addition to Canada, Japan, Brazil and Thailand. Our product is going to be able to be used around the world. Our big push is to get funding so that we can support the development of Hiltonol with our partners and get commercialized in one therapeutic area.”
For fighting a devious enemy in immunotherapy settings, Oncovir’s Hiltonol is a knight in shining armor ready to do battle as a standalone drug product and as a potent vaccine adjuvant in oncology and infectious diseases.dstock07734
Re: Steady_T post# 707795
Tuesday, July 23, 2024 8:02:47 PM
Post#
707866
of 707875
I didn't finish the list of all the acquisitions of ADCs by BPs in the past three years. I think the list is long enough. I see big money incoming soon.
AbbVie to Acquire ImmunoGen, including its Flagship Cancer Therapy ELAHERE® (mirvetuximab soravtansine-gynx), Expanding Solid Tumor Portfolio
https://investor.immunogen.com/news-releases/news-release-details/abbvie-acquire-immunogen-including-its-flagship-cancer-therapy
Orum Therapeutics Announces Acquisition of ORM-6151 Program by Bristol Myers Squibb
https://www.orumrx.com/news/orum-orm-6151-acquisition-by-bms
Tubulis Announces Strategic License Agreement with Bristol Myers Squibb to Develop Next Generation ADCs for the Treatment of Cancer Patients
https://tubulis.com/news/tubulis-announces-strategic-license-agreement-with-bristol-myers-squibb-to-develop-next-generation-adcs-for-the-treatment-of-cancer-patients-2/
Daiichi Sankyo and Merck Announce Global Development and Commercialization Collaboration for Three Daiichi Sankyo DXd ADCs
https://www.merck.com/news/daiichi-sankyo-and-merck-announce-global-development-and-commercialization-collaboration-for-three-daiichi-sankyo-dxd-adcs/
Merck Snaps Up Small Startup in $208M Deal, Seeks to Improve Safety of ADCs
https://www.biospace.com/merck-snaps-up-small-startup-in-208m-deal-seeks-to-improve-safety-of-adcs
GSK enters exclusive license agreement with Hansoh for HS-20089
https://www.gsk.com/en-gb/media/press-releases/gsk-enters-exclusive-license-agreement-with-hansoh-for-hs-20089/
LaNova Medicines Announces Global Exclusive License Agreement with AstraZeneca for LM-305, a Novel GPRC5D-Targeting Antibody Drug Conjugate
https://www.prnewswire.com/news-releases/lanova-medicines-announces-global-exclusive-license-agreement-with-astrazeneca-for-lm-305-a-novel-gprc5d-targeting-antibody-drug-conjugate-301823364.html
Eli Lilly expands ADC scope with Mablink Bioscience acquisition
https://www.pharmaceutical-technology.com/news/eli-lilly-expands-adc-scope-with-mablink-bioscience-acquisition/
Genmab buys ProfoundBio for $1.8B, adding to ADC dealmaking flurry
https://www.biopharmadive.com/news/genmab-profoundbio-adc-acquisition-buyout-seagen/712097/
Johnson & Johnson to Acquire Ambrx, Advancing Next Generation Antibody Drug Conjugates to Transform the Treatment of Cancer
https://www.janssen.com/johnson-johnson-acquire-ambrx-advancing-next-generation-antibody-drug-conjugates-transform-treatment
dstock07734
Re: None
Tuesday, July 23, 2024 3:33:33 PM
Post#
707792
of 707874
ABL Awarded $Multimillion Contract to Provide Manufacturing and Nonclinical Services to Support Development of Promising Therapeutics for the NINDS
https://ablinc.com/about-abl/news/news-item/abl-awarded-multimillion-contract-to-provide-manufacturing-and-nonclinical-services-to-support-development-of-promising-therapeutics-for-the-ninds/
Rockville, Maryland (US), November 4, 2022 Advanced BioScience Laboratories (ABL), a global Contract Development and Manufacturing Organization (CDMO) and Contract Research Organization (CRO) to the U.S. Government and biopharmaceutical industry, announced it is one of three contractors awarded an Indefinite Delivery, Indefinite Quantity (IDIQ) contract for “Manufacturing and Nonclinical Studies support for Development of Therapeutic Biotechnology Products (Biologics) for Neurological-related Disorders” by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) of the U.S. Department of Health and Human Services (HHS), contract number 75N95022D00023.
ABL & NINDS Partnership
The eight-year, multiple-award-IDIQ contract has a total potential funding value of $149.2M million. ABL, as an awardee of the IDIQ contract pool will provide NINDS current Good Manufacturing Practices (cGMP) manufacturing and Good Laboratory Practice (GLP) nonclinical (preclinical) services to support translational development of therapeutic biotechnology (biologics) products of various modalities for NIH’s drug discovery and development programs. This contract supports the NIH Biologics development projects for the NIH Blueprint Neurotherapeutics Network Biologics (BPN-Biologics) program, the NINDS Ultra-Rare Gene Therapy (URGenT) program, the Helping to End Addiction Long-term Pain Therapeutics Development Program (HEAL-PTDP), and other extramural or intramural NIH drug discovery and development programs. ABL’s portfolio of services includes feasibility studies, process and assay development, cGMP manufacturing, IND-enabling GLP safety, pharmacokinetic and efficacy studies, stability studies, and product release testing. These services are provided either at ABL facilities or at one of the 42 companies that formed the ABL Collaboratory to support this contract.
ABL’s scientists have been supporting NIH’s mission since the 1980s. Our Government Solutions staff has worked hand-in-hand with government and industry key opinion leaders (KOLs) for many years to develop novel biomedical products.
“We look forward to continuing to serve the mission of the NIH through this contract with NINDS and in support of the most innovative investigators in the field who are developing cutting-edge products that prevent, treat, and cure neurological disorders, stroke, and ultrarare genetic disease” said Marykay Marchigiani, COO of ABL.
martyDg: Let's fast forward to '29. Sawston free cash flow that year will be $1 billion. And the $ 1 billion cash received in late '24 in lawsuit settlements will still be on the balance sheet. What's the value of that to the 15 CI manufacturers?
Re: just Scottie post# 707760
Tuesday, July 23, 2024 5:11:04 PM
Post#
707820
of 707820
$0.20 is very possible; it’s a make-or-break at this point. The only near-future catalyst is approval, so if it’s disapproved, welcome to the pink sheets, possibly $0.001. If approved, then $1+. Then, move on to the next milestone, which is FDA approval, but without revenue, this won’t crawl up to $3-6.
Tuesday, July 23, 2024 3:33:33 PM
Post#
707792
of 707817
ABL Awarded $Multimillion Contract to Provide Manufacturing and Nonclinical Services to Support Development of Promising Therapeutics for the NINDS
https://ablinc.com/about-abl/news/news-item/abl-awarded-multimillion-contract-to-provide-manufacturing-and-nonclinical-services-to-support-development-of-promising-therapeutics-for-the-ninds/
Rockville, Maryland (US), November 4, 2022 Advanced BioScience Laboratories (ABL), a global Contract Development and Manufacturing Organization (CDMO) and Contract Research Organization (CRO) to the U.S. Government and biopharmaceutical industry, announced it is one of three contractors awarded an Indefinite Delivery, Indefinite Quantity (IDIQ) contract for “Manufacturing and Nonclinical Studies support for Development of Therapeutic Biotechnology Products (Biologics) for Neurological-related Disorders” by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) of the U.S. Department of Health and Human Services (HHS), contract number 75N95022D00023.
ABL & NINDS Partnership
The eight-year, multiple-award-IDIQ contract has a total potential funding value of $149.2M million. ABL, as an awardee of the IDIQ contract pool will provide NINDS current Good Manufacturing Practices (cGMP) manufacturing and Good Laboratory Practice (GLP) nonclinical (preclinical) services to support translational development of therapeutic biotechnology (biologics) products of various modalities for NIH’s drug discovery and development programs. This contract supports the NIH Biologics development projects for the NIH Blueprint Neurotherapeutics Network Biologics (BPN-Biologics) program, the NINDS Ultra-Rare Gene Therapy (URGenT) program, the Helping to End Addiction Long-term Pain Therapeutics Development Program (HEAL-PTDP), and other extramural or intramural NIH drug discovery and development programs. ABL’s portfolio of services includes feasibility studies, process and assay development, cGMP manufacturing, IND-enabling GLP safety, pharmacokinetic and efficacy studies, stability studies, and product release testing. These services are provided either at ABL facilities or at one of the 42 companies that formed the ABL Collaboratory to support this contract.
ABL’s scientists have been supporting NIH’s mission since the 1980s. Our Government Solutions staff has worked hand-in-hand with government and industry key opinion leaders (KOLs) for many years to develop novel biomedical products.
“We look forward to continuing to serve the mission of the NIH through this contract with NINDS and in support of the most innovative investigators in the field who are developing cutting-edge products that prevent, treat, and cure neurological disorders, stroke, and ultrarare genetic disease” said Marykay Marchigiani, COO of ABL.
Re: TTsr post# 707797
Tuesday, July 23, 2024 4:04:10 PM
Post#
707805
of 707819
Here are the two other contractors.
Provide support for both Biologics current good manufacturing practices (cGMP) manufacturing and GLP nonclinical services, including execution of the studies and completing study reports and documentation that will enable regulatory filing and evaluation of biological therapeutics in clinical trials for NIH drug development programs. The vehicle supports the NIH biologics development projects for the NIH Blueprint Neurotherapeutics Network Biologics (BPN-Biologics) program, the NINDS Ultra-Rare Gene Therapy (URGenT) program, the Helping to End Addiction Long-term Pain Therapeutics Development Program (HEAL-PTDP), as well as other extramural or intramural NIH drug discovery and development programs.
Leidos
https://www.highergov.com/idv/75N95022D00022/
Battelle Memorial Institute
https://www.highergov.com/idv/75N95022D00021/
Battelle, AmplifyBio, Andelyn Biosciences Win Research Contract for National Institute of Neurological Disorders and Stroke
https://www.battelle.org/insights/newsroom/press-release-details/battelle-amplifybio-andelyn-biosciences-win-research-contract-for-national-institute-of-neurological-disorders-and-stroke
The team of Battelle, AmplifyBio and Andelyn Biosciences has won a seat on an eight-year, $149 million indefinite delivery, indefinite quantity (IDIQ) contract vehicle for the National Institute of Neurological Disorders and Stroke. As one of the prime contractors on the multi-award IDIQ, the team will provide manufacturing and nonclinical support for translational development of therapeutic biotechnology products in the National Institutes of Health’s drug discovery and development program that addresses neurological conditions.
“The contract will be used to advance innovative therapies, including cell and gene therapy, for a broad variety of neurological diseases,” said Drew Cawthon, Business Line Director of Battelle’s Life Science Research. “We’ll be researching new and novel ways to treat rare diseases, ones that don’t yet have effective treatments.”
“The success of this proposal bid allows AmplifyBio to demonstrate our continued partnership with Battelle and formalizes a new partnership with Andelyn Biosciences,” said Jerry Hacker, EVP and Chief Commercial Officer, AmplifyBio. “This highlights the types of collaborations possible in the growing life science hub in Central Ohio. We look forward to bringing our expertise in advanced therapy analytics and preclinical study capabilities to accelerate groundbreaking therapies for neurological conditions.”
Eric Blair, Chief Commercial Officer at Andelyn, added: “We are proud to be supporting this research program by NINDS. At Andelyn, we are wholly committed to making an impact when it comes to manufacturing therapies, particularly when it comes to treating rare disease. We are looking forward to working alongside our partners and providing hope to the patients impacted.”
Battelle offers assay support and integration services to support regulatory approval, as well as decades of federal government contracting experience that supports its position as the prime contractor. Beyond the significant technical and program management expertise, the team is unique in that all team members are local to Central Ohio.
“What we have in Central Ohio rivals anything available on a national or international stage,” said Brian Burback, Battelle chemist in the Life Science Research business line. “The specific scope of work was an incredible opportunity to pull together a Central Ohio team.”
All three of the teams actively collaborated on the winning proposal. As they bid on task orders, they expect for each partner to receive similar shares of the work, relying on the differentiated strengths of each organization to meet the client’s needs.
Re: Nemesis18 post# 707662
Tuesday, July 23, 2024 9:52:38 AM
Post#
707688
of 707739
How about you open the following files and search "murcidencel" first?
https://www.derbyshiremedicinesmanagement.nhs.uk/assets/High_cost_drugs/NHSE%20ICB%2024-25.xlsx
https://www.england.nhs.uk/wp-content/uploads/2023/12/23-25NHSPS-amendment-consultation-annex.xlsx
https://www.sps.nhs.uk/wp-content/uploads/2022/10/Prescribing-Outlook-2023-amended-Mar-24.xlsx
Guest blog: “It doesn’t seem right to think about dying at 26”
BRAIN TUMOUR RESEARCH
2 min read
During Glioblastoma (GBM) Awareness Week, Charlie Pearson shares how it feels to be preparing for his death when he should have so much life left to live…
I have always been the sort of person who loves language. I love how words flow.
But these days, I open my mouth and I’m left hanging, my mind whirring with the effort of trying to remember what I want to say. And then I have to stop because the more I think, the more I feel like I’m going to have a seizure.
A year ago, I found out I had a glioblastoma (GBM) – an aggressive brain cancer that comes with a prognosis of 12 to 18 months. And so now I find myself having to think about the end of my life, when it feels like I was only just beginning.
I’d been flying high at work, carving out a career in the civil service. I’d moved to London from Essex and landed a promotion. It was a high stress environment but I thrived on it. Big dinner parties with friends, nights at the opera and trips to Europe with my partner, Ollie, were top of my to do list.
Charlie and Ollie at Munich Opera House
Life was full and exciting. But then I had a seizure on the tube to work one morning in July 2023. In a way, I was waiting for it. I had suffered a seizure once before, aged 21, in 2019, and scans had shown I had a grade 2 astrocytoma. The news hit me hard and I felt like giving up.
But after going through surgery, an infection and more surgery to reconstruct part of my skull, I felt a renewed lease of life. My medical team were honest – the tumour would come back. But if there was no reoccurrence within four years, it would take a lot longer to return.
I decided I wasn’t going to waste a minute and threw myself into living as though I didn’t have this disease.
And I almost hit that four-year mark. But then, after what turned out to be my last holiday to Portugal with Ollie, came the news that I had cancer spreading across both sides of my brain.
That whole time is a blur. An awake craniotomy, radiotherapy and chemotherapy. The treatment was absolutely awful, I was violently ill. You wouldn’t put your worst enemy through it.
My hair fell out, the steroids made my face balloon and I still find it hard to look in the mirror.
And though I’ve finished my treatment, it’s clear I’ll never be the same again. My personality has changed, I’m constantly battling fatigue and memory loss and I’m easily overstimulated. I live at home now so my parents can help take care of me.
And yet, I’m not done with living yet. Though I can’t do the job I loved anymore, I need something to get up for. So, I’m hoping to begin volunteering in a school, reading to children and helping them to fall in love with language too.
The only way I can get through the days and keep going is to accept my fate. This brain tumour is going to take my life. It doesn’t seem right to have to think about dying at 26, but I don’t feel angry. I’m actually very lucky to be given the time I have with the people I love because I know a lot of people get less time than me.
At a recent wedding with friend Katie
I’ve written my will, told my mum what I’d like for my funeral, chosen the songs to be played and asked some special people to speak. These aren’t things I expected to have to think about for many years but in a way it felt good to get it done.
Now I just live in the moment. Spending time with my mum, dad, twin brother Davey, Ollie and my friends who have all been incredibly supportive.
Charlie with his parents and twin Davey
My story may not be as long as I would have wished but by helping to raising awareness of GBMs and the work that Brain Tumour Research does, I hope I can help prevent others from suffering the same fate.
If you’ve been touched by Charlie’s story, you can help us find a cure by donating whatever you can to fund the fight against brain tumours. Together, we can make a difference. To make a one-off or monthly donation, please click here
Related reading:
Charlie’s story
How will we find a cure for GBMs?
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@debog93
https://www.bizjournals.com/sanfrancisco/news/2024/07/18/cancer-sean-parker-immunotherapy-cell-therapy.html
https://www.parkerici.org/the-latest/parker-institute-commits-additional-125m-for-audacious-mission-to-cure-cancer/
The Parker Institute for Cancer Immunotherapy Awards More Than $1 Million to Four Early Career Investigators
06.27.24
Fascinating to see how every single one of the different immunotherapy research works of these investigators receiving these awards have synergy and show huge potential benefits of combining with DCVax:-
Research focus on interrogating cytotoxic T cell function with CRISPR screens holds immense potential for synergy with DCVax technology in cancer immunotherapy.
Parker Bridge Fellow Zachary Steinhart, PhD, Gladstone Institutes,
Understanding the Players:
Cytotoxic T cells (CTLs): These are the assassins of the immune system, capable of directly recognizing and destroying cancer cells. However, tumors often evolve mechanisms to evade CTL attack.
CRISPR screens: This powerful technology allows for high-throughput interrogation of gene function. By knocking out genes in CTLs, you can identify those crucial for their anti-tumor activity.
DCVax technology: This personalized immunotherapy platform uses a patient's own dendritic cells (DCs) – the master orchestrators of the immune response – to prime CTLs against tumor-specific antigens.
Synergy and Potential:
Identifying Targets for Enhanced DCVax Efficacy:
CRISPR screens can pinpoint genes in CTLs that, when modified, enhance their killing capacity, persistence, or ability to overcome tumor immunosuppression.
These genes become prime targets for genetic engineering using CRISPR in the DCVax platform. Imagine creating "supercharged" CTLs armed with enhanced anti-tumor properties by:
Boosting expression of co-stimulatory molecules: Amplifying signals that activate CTLs more effectively.
Silencing inhibitory receptors: Removing the "brakes" that tumors use to suppress CTL function.
Enhancing CTL infiltration into tumors: Overcoming physical barriers that prevent CTLs from reaching cancer cells.
Optimizing Antigen Selection for DCVax:
CRISPR screens can identify novel tumor-associated antigens that are highly specific and immunogenic, meaning they are more likely to elicit a strong CTL response.
Incorporating these superior antigens into the DCVax platform could lead to more effective and targeted immunotherapy.
Predicting and Overcoming Treatment Resistance:
CRISPR screens can help identify genes involved in resistance to DCVax therapy. This knowledge allows for:
Developing strategies to circumvent resistance: For example, combining DCVax with drugs that target the resistance mechanisms.
Identifying patients most likely to benefit from DCVax: Leading to more personalized treatment strategies.
Implications:
This synergistic approach holds tremendous promise for improving cancer immunotherapy by:
Enhancing the efficacy of DCVax technology:
Leading to more durable and complete responses in cancer patients.
Expanding the applicability of DCVax:
Potentially targeting a wider range of cancers and patients.
Developing more personalized and precise cancer treatments: Tailoring therapies based on individual tumor characteristics and patient immune profiles.
Conclusion:
The combination of your research on CTL function using CRISPR screens with the DCVax platform represents a powerful convergence of cutting-edge technologies. This synergy has the potential to revolutionize cancer immunotherapy by generating safer, more effective, and personalized treatments for patients. (Gemini-1.5-Pro)
Synergy Implications and Possibilities for Combining Novel Hybrid Synthetic Receptors with DCVax Technology for Enhanced Solid Tumor T-cell Therapy
Parker Scholar Maxwell Foisey, PhD candidate, the University of California, San Francisco,
Your research focus on novel hybrid synthetic receptors delivering immunomodulatory payloads to enhance solid tumor T-cell therapy holds immense potential, especially when considering synergy with DCVax technology. Let's break down the potential implications and possibilities:
Understanding the Players:
Hybrid Synthetic Receptors:
These are engineered receptors designed to recognize specific tumor antigens and activate T cells. The "hybrid" aspect implies combining different functionalities, such as antigen recognition domains from antibodies with signaling domains from T-cell receptors, potentially improving targeting and activation. Delivering immunomodulatory payloads directly to the tumor microenvironment can further enhance the immune response.
DCVax Technology: This personalized immunotherapy platform uses a patient's own dendritic cells (DCs), key orchestrators of the immune system. DCs are extracted from the patient's blood, primed with tumor-specific antigens (often derived from the patient's tumor), and then reinfused. These "educated" DCs then prime T cells to recognize and attack the tumor cells.
Synergy Potential and Combination Possibilities:
Combining these two approaches could lead to synergistic effects through several mechanisms:
Enhanced T-cell Priming and Activation:
DCVax: Primes T cells against a broad repertoire of tumor antigens, potentially including neoantigens specific to the individual's tumor.
Hybrid Receptors: Enhance T-cell activation and tumor recognition through:
Increased binding affinity and specificity to tumor antigens.
Delivery of co-stimulatory signals to T cells within the tumor microenvironment, overcoming immunosuppressive signals.
Release of immunomodulatory payloads that promote T-cell proliferation and persistence.
Overcoming the Immunosuppressive Tumor Microenvironment:
DCVax: Can induce a systemic anti-tumor immune response, potentially impacting the tumor microenvironment.
Hybrid Receptors: Can be engineered to:
Block inhibitory checkpoints within the tumor microenvironment (e.g., PD-1, CTLA-4), unleashing T-cell activity.
Deliver payloads that directly target and eliminate immunosuppressive cells within the tumor, such as regulatory T cells (Tregs) or myeloid-derived suppressor cells (MDSCs).
Improved Targeting and Reduced Off-Target Effects:
DCVax: While generally safe, off-target effects can occur due to the broad immune response generated.
Hybrid Receptors: Can enhance specificity by targeting T cells only to tumor cells expressing the specific antigen, potentially reducing off-target toxicity.
Combination Strategies:
Sequential Treatment:
DCVax could be administered first to prime the immune system, followed by T cells engineered with hybrid receptors to enhance tumor infiltration and killing.
Concurrent Treatment:
Simultaneous administration of DCVax and engineered T cells could lead to synergistic effects within the tumor microenvironment.
Research Avenues:
Optimizing Hybrid Receptor Design:
Explore different antigen targets, co-stimulatory domains, and immunomodulatory payloads to maximize synergy with DCVax.
Investigating Combination Regimens:
Determine the optimal timing and dosing of DCVax and engineered T-cell therapy for different tumor types.
Evaluating Biomarkers:
Identify predictive biomarkers for treatment response to personalize therapy and optimize patient selection.
Conclusion:
The combination of novel hybrid synthetic receptors and DCVax technology holds significant promise for improving solid tumor T-cell therapy. By harnessing the strengths of both approaches, this synergistic strategy could lead to more effective and durable anti-tumor immune responses. Further research is warranted to explore the full potential of this exciting combination. (Gemini-1.5-Pro)
Metastatic Stem Cells, Immune Evasion, and DCvax: A Potential Synergy
Parker Scholar Debolina Ganguly, PhD, Dana-Farber Cancer Institute,
Metastatic cancer remains a significant challenge in oncology, largely due to the ability of disseminated tumor cells to evade the immune system and resist therapy. Emerging research points to a subpopulation of cells within tumors, termed metastatic stem cells (MSCs), as key drivers of this immune evasion and treatment resistance. Understanding the mechanisms by which MSCs suppress anti-tumor immunity is crucial for developing effective therapeutic strategies, and recent findings suggest promising synergy with DCvax technology.
Mechanistic Underpinnings of MSC-Mediated Immune Suppression:
MSCs employ a multi-pronged approach to suppress anti-tumor immune responses:
Immunosuppressive Cytokine Milieu:
MSCs secrete a cocktail of immunosuppressive cytokines, including:
TGF-ß: This cytokine inhibits the proliferation and cytotoxic activity of CD8+ T cells, key players in anti-tumor immunity.
IL-10: IL-10 suppresses the function of antigen-presenting cells (APCs) like dendritic cells (DCs), hindering their ability to prime effective T cell responses.
PGE2: Prostaglandin E2 (PGE2) promotes the differentiation of immunosuppressive regulatory T cells (Tregs) and inhibits the activity of natural killer (NK) cells.
Recruitment of Immunosuppressive Cells: MSCs actively recruit immunosuppressive cells to the tumor microenvironment:
Myeloid-derived suppressor cells (MDSCs): These cells suppress T cell responses through various mechanisms, including the production of reactive oxygen species (ROS) and the depletion of essential amino acids.
Regulatory T cells (Tregs): Tregs suppress the activity of effector T cells, maintaining immune tolerance to tumor antigens.
Impaired Antigen Presentation: MSCs can directly suppress the function of APCs:
Downregulation of MHC molecules: MSCs express lower levels of major histocompatibility complex (MHC) molecules, reducing their ability to present tumor antigens to T cells.
Inhibition of DC maturation: MSCs can inhibit the maturation of DCs, preventing them from effectively priming anti-tumor T cell responses.
DCvax Technology: A Potential Ally in Overcoming MSC-Mediated Suppression
DCvax is a personalized immunotherapy approach that utilizes a patient's own DCs, key orchestrators of the immune response, to stimulate a targeted attack against cancer cells. Here's how DCvax technology holds the potential to synergize with strategies targeting MSC-mediated immune suppression:
Enhanced Antigen Presentation:
DCvax involves ex vivo loading of DCs with tumor-associated antigens, bypassing the need for antigen presentation by tumor cells or potentially suppressed APCs within the tumor microenvironment. These activated DCs can then effectively prime tumor-specific T cells.
Overcoming Immunosuppressive Signals:
DCvax-activated DCs are matured and activated ex vivo, making them less susceptible to the immunosuppressive signals present in the tumor microenvironment. These activated DCs can then effectively prime tumor-specific T cells despite the presence of inhibitory cytokines like TGF-ß and IL-10.
Induction of Long-lasting Immunity: DCvax aims to induce a robust and long-lasting anti-tumor immune response by generating memory T cells. These memory cells can provide sustained tumor surveillance and control, even if MSCs persist.
Potential Combination Strategies and Future Directions:
Combining DCvax with therapies targeting MSCs or their immunosuppressive mechanisms holds significant promise:
Targeting MSCs Directly:
Therapies aimed at eliminating MSCs, such as targeted antibodies or small molecule inhibitors, could synergize with DCvax by reducing the overall immunosuppressive burden within the tumor microenvironment.
Blocking Immunosuppressive Pathways:
Combining DCvax with inhibitors of immunosuppressive cytokines (e.g., TGF-ß inhibitors) or checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies) could further enhance anti-tumor immunity by unleashing the full potential of DCvax-activated T cells.
Combination with Other Immunotherapies:
Exploring the combination of DCvax with other immunotherapies, such as adoptive cell transfer (ACT) or oncolytic viruses, could lead to synergistic anti-tumor effects.
Further research is crucial to fully elucidate the complex interplay between MSCs and the immune system, as well as to optimize combination strategies involving DCvax. However, the potential for synergy between these approaches offers a compelling avenue for developing more effective treatments for metastatic cancer. (Gemini-1.5-Pro)
Harnessing Engineered CD47 with DCVax for Cancer Immunotherapy:
Parker Scholar Sean Yamada-Hunter, PhD, Stanford Medicine
Synergy, Potential, and Benefits
Combining engineered CD47 blockade with DCVax technology represents a promising avenue for cancer immunotherapy, potentially offering synergistic benefits and accelerating clinical translation. Let's break down the components and their interactions:
1. CD47 and its Role in Immune Evasion:
CD47 is a cell surface protein overexpressed on many cancer cells.
It acts as a "don't eat me" signal by binding to SIRPa receptors on macrophages and other phagocytic cells, inhibiting their ability to engulf and destroy the tumor cells.
2. Engineered CD47 Blockade:
This strategy utilizes monoclonal antibodies or other engineered molecules to block the interaction between CD47 and SIRPa.
This blockade prevents cancer cells from evading the immune system, allowing macrophages to recognize and eliminate them.
3. DCVax Technology:
DCVax is a personalized cancer vaccine platform that utilizes dendritic cells (DCs), the most potent antigen-presenting cells in the immune system.
The process involves extracting a patient's own DCs, priming them with tumor-specific antigens (often from the patient's tumor), and injecting them back into the patient.
This approach educates and activates the patient's T cells to recognize and destroy cancer cells expressing those specific antigens.
Synergy and Potential Benefits of Combining Engineered CD47 Blockade with DCVax:
Enhanced Antigen Presentation and T Cell Priming:
By blocking CD47, macrophages can effectively engulf tumor cells, process tumor antigens, and present them to T cells, enhancing the efficacy of DCVax in priming tumor-specific T cell responses.
Overcoming Immune Suppression in the Tumor Microenvironment:
CD47 blockade not only promotes phagocytosis but can also reverse the immunosuppressive environment often found within tumors. This creates a more favorable environment for the activated T cells generated by DCVax to infiltrate and eliminate cancer cells.
Synergistic Tumor Cell Killing:
The combination allows for a two-pronged attack on cancer cells. Macrophages directly eliminate tumor cells through phagocytosis, while DCVax-activated T cells target and destroy tumor cells through cell-mediated cytotoxicity.
Potential for Durable Immune Responses:
DCVax, by activating T cells, can potentially establish long-lasting immunological memory, providing sustained protection against tumor recurrence even after the initial treatment course. Combining it with CD47 blockade could further amplify and prolong this effect.
Rapid Clinical Translation:
Both engineered CD47 blockade and DCVax have shown promising results in clinical trials as standalone therapies. Combining these approaches, which already have established safety and efficacy profiles, could potentially accelerate the clinical translation process.
Challenges and Future Directions:
While promising, further research is needed to:
Optimize the timing and dosing of both therapies for optimal synergy.
Identify potential biomarkers to predict patient response to this combination therapy.
Investigate the efficacy of this combination in various cancer types.
In conclusion, combining engineered CD47 blockade with DCVax technology holds significant potential for a synergistic and potent cancer immunotherapy approach. This combination could enhance tumor cell killing, overcome immune suppression, and potentially lead to durable anti-tumor immunity, paving the way for rapid clinical translation and improved outcomes for cancer patients (Gemini-1.5-Pro)
https://parkerici.org/the-latest/parker-institute-commits-additional-125m-for-audacious-mission-to-cure-cancer/
Parker Institute Commits Additional $125M for Audacious Mission to Cure Cancer
https://parkerici.org/the-latest/the-parker-institute-for-cancer-immunotherapy-awards-more-than-1-million-to-four-early-career-investigators/
dstock07734
#dcvax $nwbo #gbm
— Peter Davis (@peter_brit) July 23, 2024
Excellent post by @d_stock07734
In the PR, LP mentioned about how challenging to isolate adherent cells like dendritic cells without damaging them. I recall she even used the word "barnacle" to illustrate how dendritic cell can be adherent to vessels. I did… pic.twitter.com/YF4Yoz1USq
dstock07734
Re: ae kusterer post# 707540
Monday, July 22, 2024 12:30:53 PM
AE,
Thanks for the transcript.
In the PR, LP mentioned about how challenging to isolate adherent cells like dendritic cells without damaging them. I recall she even used the word "barnacle" to illustrate how dendritic cell can be adherent to vessels. I did keep track of NWBO hiring records on flaskworks. If I am not mistaken, there are only three new employees joining flaskworks who came out of college fresh. It doesn't strike me that those new employees have enough professional experience to tackle very challenging technical issues. On the other hand, the founder of Flaskworks, Shashi Murthy left NWBO in January 2022 to have a new start-up.
Co-Founder & Chief Technology OfficerCo-Founder & Chief Technology Officer
Nanite · Full-timeNanite · Full-time 2022 - Present · 2 yrs 7 mos2022 to Present · 2 yrs 7 mos Boston, Massachusetts, United StatesBoston, Massachusetts, United States
• Nanite designs fit-for-purpose non-viral delivery vehicles for gene therapies using machine learning.
• Current partners include the Bill & Melinda Gates Foundation, the CMT Research Foundation, and the Cystic Fibrosis Foundation in addition to undisclosed biotech and pharma companies.
But after hearing about Corning from ASM, I had Eureka moment. When did Corning have their FBR system ready? According to the waybackmachine, the webpage on FBR was first setup in July 2022. It is fair to say that FBR system was ready for marketing several months after Shashi left. We can also see that West Pharmaceutical was in collaboration with Corning to develop new vial system for cell therapy. It makes sense that NWBO needs a big supplier which has enough manufacturing capacity to supply huge number of upgraded version of flaskworks since IMO all the BPs which have ADCs and t-cell engagers in their portfolio have to franchise the system.
https://www.corning.com/worldwide/en/products/life-sciences/products/bioprocess/ascent-fbr-system.html
https://web.archive.org/web/20220801000000*/https://www.corning.com/worldwide/en/products/life-sciences/products/bioprocess/ascent-fbr-system.html
Yeah. I'm taking too much time, so I have to hurry up. Flaskworks . . . I'll just say, 18 months ago, we, they had only developed one approach for the system. It was a good approach. It was attractive. It's part of why we acquired them from Corning, but it wasn't necessarily, specifically as optimized as we would like it to be. So over these 18 months more, we developed two other fundamentally different approaches to the automation, the closing, magic word, and automation of the manufacturing.
Before the acquisition by NWBO, Flask Works had developed only one approach for its system. It was a good approach and part of the reason why NWBO acquired it from Corning. Still, it wasn't as optimized as NWBO wanted. So over the last 18 months since the acquisition, Advent and NWBO have developed two additional, fundamentally different approaches to the automation and the closing of the manufacturing process. Extensive comparative testing between the two evaluated how cells did with one approach or another looking at parameters such as the yield and the stress on the cells.
dstock07734
Monday, July 22, 2024 2:28:12 PM
Not sure if this was mentioned before.
In collaboration with AZN, Dr. Timothy Cloughesy is the PI for a clinical trial using ADC from AZN which targets EGFR highly overexpressed in GBM. The trial is also testing a new imaging technology.
18F-FDG PET imaging may help to detect changes in tumor glucose utilization, which may allow investigators to obtain an early read out on the impact of osimertinib on recurrent glioblastoma patients whose tumors have EGFR activation.
18F-FDG PET and Osimertinib in Evaluating Glucose Utilization in Patients With EGFR Activated Recurrent Glioblastoma
https://clinicaltrials.gov/study/NCT03732352
NIMG-34. QUANTIFICATION OF GLYCOLYTIC FLUX REDUCTION IN RECURRENT GLIOBLASTOMA AFTER EGFR INHIBITION USING MOLECULAR MR-PET
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9660931/
NIMG-36. MR PERFUSION IS A BETTER PREDICTOR OF TUMOR RECURRENCE AND TREATMENT RESPONSE THAN STANDARD MRI IN SOME OLIGODENDROGLIOMA PATIENTS
https://academic.oup.com/neuro-oncology/article/24/Supplement_7/vii171/6826366#google_vignette
exwannabe: When you say " Even an exact copy of DCVax-L would not infringe as those patents are all expired." , you are barking up the wrong tree. UCLA, the MHRA, Oncovir, Nature , and Roswell would not be doing transactions with $nwbo unless their patent attorneys had assured those institutions that dc vax l and dc vax direct are proprietray therapies with long term patent protection.I suggest you study the last five years of twitter postings by @henrymuney . He is the best $nwbo patent researcher. Also, @hoffmann6383 has analyzed several NWBO patent situations.
P.S. Your nwbo disinformation is beyond the pale. It strikes me a criminal, warranting free room and board so you have time to think over whether or not you want to remail a U.S. citizen.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174785640
exwannabe
Re: Horseb4CarT post# 707358
Sunday, July 21, 2024 11:25:17 AM
Post#
707395
of 707591
Does this encroach on DCVax patents?
It certainly does not now, as clinical trials are fair use even if infringing.
It does not seem particularly likely it would infringe. It s clearly a fairly different process. Remember that ATL-DCs existed even before NWBO did. There are many DCs out there that do infringe. Even an exact copy of DCVax-L would not infringe as those patents are all expired.
Sunday, July 21, 2024 11:25:17 AM
" Even an exact copy of DCVax-L would not infringe as those patents are all expired."
#DCVax-L facts. Match the references to the items in the screenshot.
— Henry (@HenryMuney) January 4, 2023
1. SAP https://t.co/1bPnvQoKBT
2. Contemporaneous External Controls https://t.co/G6BhQPSeZM
3. DCVax-L = ATL-DC https://t.co/QbqNHXYKYK
4. Crossover arm https://t.co/KX6dqxmFOU
5. Patient-level data$NWBO pic.twitter.com/3ID2wMKBT7
beartrap: In the ASM transcript below , LP elucidates three phases of MHRA review, adding up to 210 days . If NWBO's start date is its validation date, 1/24/24,then 8/24/24 is the mhra 's deadline . Caveat:when the mhra announced the 150 day guidance in 2020, did they molt their organization to make the new deadlines possible?
Re: XMaster2023 post# 707420
Monday, July 22, 2024 7:36:08 AM
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of 707537
This Thursday is the beginning of the next monthly meeting of the Commission on Human Medicine (CHM) where MRHA officials discuss new medicines in the approval pipeline. Yes, we could be approved during or following this two-day meeting. It is approximately 6 months since we received MAA validation on January 24 or 180 days since that approval. If we're on the 150-day schedule for approval and if MHRA is sticking to it, then this Thursday would have given us 30 days of time-off to address questions from the MRHA. Remember, the 60-day time-off is just the maximum amount of time companies are allowed for a single time-out period. (Companies can take two time-outs during the 150-day MAA process).
XMaster, thanks for pointing out that Thursday is nine days before the date that MHRA announces medicines it has approved.
Approval could be after the 9 days but not historically before. As noted the next date is this Thursday 7/25/24.
The next meeting of the CHM is the last Thursday/Friday is August: August 29-30.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174721256 $nwbo
@alphavestcap
210 days; 7 months; "but we don’t, we do not have confirmation of that".
"We're well underway. We believe the MHRA is following the 150-day process that they have, but we don’t, we do not have confirmation of that. We don't have a way to be sure of that, to know it for sure, but we believe that. It, the “150 days,” quote, unquote, involves approximately 3 stages, and the time frame of each stage is approximate. So it's not, you know, on the button.
The first stage is approximately 80 days of initial review of the application. The second stage is approximately 60-day clock stop, when the agency is going to deliver a list of questions to us, as they do in all these processes. It's not just us. They'll deliver a list of questions. They'll ask for supplementary information, all of that. And, and we will try to respond as fast as we can, which is part of why we're trying to guess what they might might ask, and try to already kind of prepare.
The 3rd stage, which will come after the 60-day clock stop, or however long the clock stop turns out to be, to provide all the answers and info, additional information. The third stage is approximately 70 days of further review, and reaching a decision. Again, the the timelines are approximate. As as far as we've seen, there is not an equivalent thing in the UK that's similar to a PDUFA date in the US. You know, under the legislation in the US, you know, FDA can have a target date for giving you a decision.
We don't have a target date. It'll be what it'll be, okay? And those approximate time frames of those 3 stages that I described, of course, depend also on MHRA's workload, and what backlog they have, and so forth. So that's the approximate process, and the approximate timelines."
ae kusterer
Followers 113
Posts 8675
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ae kusterer
Re: None
Monday, July 08, 2024 6:08:08 PM
Post#
704648
of 707545
hyperopia
Transcript of 2023 ASM held June 29, 2024
https://nwbio.com/audio-of-nwbio-2023-annual-shareholders-meeting/
Having concluded the formal business, we have no other business that was properly brought before the annual meeting of stockholders. Within 4 business days, we will provide the final voting results in a form 8k filed with the SEC, Securities and Exchange Commission. I would now like to take this opportunity for an information discussion, informal information discussion, in regard to questions submitted by stockholders in advance of the meeting. We may have to make this point. We may make forward looking statements during this discussion, and our actual results may differ materially from those forward looking statements.
You should not rely upon forward looking statements, and you should read Northwest Biotherapeutics Inc. periodic filing with the US Securities and Exchange Commission for a nonexclusive list of risk factors related to our business and operations that could cause actual results to differ materially from any forward looking statements provided during this meeting, and discussion. And now without further ado, we'll transition into that discussion. So now it can be a little more informal. Right?
This is meant to be a discussion of questions, that we're aware of, that shareholders have submitted or shareholders have raised with us. First thing that, what? Before I dive into the discussion, I think all of us at Northwest, I speak for all of us, wanna really thank all the stockholders for the tremendous voter turnout, and the tremendous, number of shares voted for this annual meeting. We really appreciate it, and we really appreciate the positive votes.
And we, we're just tremendously thankful and appreciative for that. We got a lot to discuss today, and we hope you're gonna find it exciting. And you're gonna leave the meeting feeling as excited as we do about the progress we've been making, and what our plans look like going forward. We plan to spend up to about an hour in this discussion, and we will, I will go through kind of a lot of information, that we've collected and that we think covers most of the questions, that we're aware of, that have come from shareholders. So I'm gonna start by, I'm gonna talk about the MAA, about developments at the Sawston facility, about progress with FlaskWorks. Also, gonna talk about some of the new exciting IP that we've acquired, and an update on our groundbreaking lawsuit against the folks that we believe have been manipulating our stock price.
So that'll be a kind of recap of where have we come in the last 18 months since the last annual meeting of shareholders. It's been a a busy period. After reviewing, the recapping the past 18 months, we're gonna look forward. And I'll describe our planning and our priorities for the next approximately 18 months.
And we think we hope that you'll find that exciting at with, a lot of anticipated, growth areas and potential progress. So, I wanna just go through some of these particular subject areas, for the last 18 months. So recapping where we've come to, over the last 18 months. First of all, near and dear to all of our hearts, is the MAA, for the commercial approval, application for the commercial approval of our DCVax-L product for glioblastoma brain cancer in the UK. And during this past period, key things that have been accomplished relating to this.
First of all, as you may recall, there were quite a few very significant prerequisites, that we had to complete before we were even eligible to apply. And that was in addition to the clinical trial results from our phase 3 trial. So we had to get 3 licenses for the Sawston facility. We had to get the initial license. We had to get a human tissue authority license. And then, most importantly, we had to get the MIA commercial license.
And that license, which was obtained in March of last year, was one of the first that's been granted for cell therapies in the UK. All of those licenses, the work was done, and the license was obtained, by Advent Bioservices, that worked with us. Another key, prerequisite that we had to do before being eligible to apply with the MAA, related to pediatric, treatments. We had to have a pediatric investigation plan, a PIP, which seems like a very English term.
And, the PIP had to be submitted to the regulator, and approved by the regulator, MHRA. And, so that was accomplished, and in fact, was accomplished in, what we understand to be, approximately half the usual amount of time. MHRA has been wonderful. They have given us rapid turnarounds, more than we could have expected or hoped for, in the steps that we've had with them so far. That doesn't necessarily predict anything, but it's been it's been a really great experience so far.
So completing all of those prerequisites, there were a lot of preparations as well, that kind of our surrounding context of the application itself. Pulling together the enormous, I mean it’s, it's just an enormous paper exercise, the trial master file. I don't even, I mean, I'm told it's a couple hundred linear feet of paper. I've seen it. I haven't measured it.
It's ginormous, and you cannot have any gaps. And when the inspectors come and they say, I wanna see the lab tests for patient X at clinical trial site Y, you have to be on top of that, and go right to it, and pull that page right out, and be ready for them. And we're talking an enormous trial master file. This phase 3 trial was one of the largest clinical trials of any, of a cell therapy product, particularly a personalized cell therapy product, that anybody has conducted.
And the trial master file is correspondingly enormous. That's just an example to give you a flavor. There's just a such an enormous amount, particularly to prepare for inspections, and that's a common theme you're gonna hear. We have been working our tails off with teams of consultants, because everybody's going to be inspected. We, the sponsor, are gonna be inspected. The contract research organization, who conducted the trial, is gonna be inspected. The document, the trial master files, its own, its own inspection. The independent database company that held the database for the trial will be inspected, the hospital sites, selected ones that were trial sites, are gonna be inspected.
So what I just described as the glimpse, the example, of the trial master file, every one of these parties has to have everything shipshape. And when they come with inspectors, our understanding from our advisers, is they will send a team of inspectors. Two, three, four inspectors, and they'll stay for a week.
That is a big undertaking. So we've been spending enormous amounts of time with all our teams of consultants preparing for all of those things. And we have gone through, audits, mock inspections. We hire people who used to be inspectors for regulatory agents and are now consultants, and we've gone through mock inspections. And each cycle is several months, and we get a report and then fix those things.
And so, anyway, that gives you a bit of a flavor. The drafting of the MAA package itself was a year long process as everybody knows. It was our Christmas present last year (haha) to to ourselves and everybody. Got it submitted on December 20th this past year, and had been working with medical writers since the fall of the year before. It was a multi thousand page, submission.
And then in the period since the submission, of course, there's been post-filing support. One of the things we are trying to do, working with consultants, a little bit like the practice inspections. We're trying to guess. We're trying to predict, what kind of questions might MHRA ask us about the package we submitted? And what kind of supplementary information might they ask us for? So that, to the extent possible, to send, to whatever extent we've guessed right with the guidance from all our advisors, who are experts in this, that will enable us to do a faster turnaround time.
That's the whole idea. We wanna try to keep the momentum, and keep up with path, rapid turnaround time. So that's a big area. As I think you know, also during this past 18 months, we we conducted and carried out and then publicly presented, all the, the results of our mechanism of action studies. These were, studies about the underlying biology of how DCVax works.
And our our chief technical officer, doctor Bosch, presented all that information in a company presentation during ASCO last year, and it was tremendously important because it showed with the underlying biology that DCVAX is what we've always hypothesized, it is. That it gave support for the hypothesis that it's a broad spectrum treatment. We reported that, in the examples that were studied, in those mechanism of action studies, the dendritic cells were picking up, and from the tumors tissue sample, the lysate, and presenting to the T-cells over 600 different tumor targets. So when we say it's a broad spectrum treatment, you know, that gives you a flavor of it. And those mechanism of action studies were really important to add more scientific underpinning that supports the clinical trial results that we've seen in the patients, and help support our MAA.
And we, it was very important, you know, we use proteomics technologies that are relatively recently developed. You know, proteomics, the study of the proteins, active agents, are not as far along as genomic, tools. And so we were using quite recent technologies in doing these studies, and that was really important.
We . . . on another front, we do continue to follow our patients from the phase 3 trial. We do still have patients alive. I'll remind you that the last patient was enrolled in November of 2015.
We also have, continuing our ongoing compassionate use program, we have not had as much activity in that while we've been so occupied with the MAA. But that program continues to give us really valuable real-world experience. You know, in a clinical trial, you try to do everything as cookie cutter as possible, as homogeneous, the same as possible, but that's not the way the real world is. And so, the compassionate use program has been so valuable for us because we've gained a tremendous amount. And we still are gaining tremendous amount of real world experience, basically practicing for when we're able to be commercial.
So we have patients who their tumor tissue sample isn't in the condition that it's supposed to be, or it hasn't been frozen quite the right way, or it was frozen several years ago, or the patients are way outside the age range. We have patients in their eighties, and upper eighties. So lots of real-world circumstances that, that's really been valuable for us. And, I think it's been very valuable for the patients too, which is quite important, and we are learning lessons. We have some very nice long term survivors, 8, 9, 10 years. And, so we are learning lessons from the cases of long term survivors as well.
Okay, another huge area of activity over these past 18 months has been in the Sawston facility. The development of it, not just the licenses, which I've already touched on. But let me just let me just, for a moment of history here, remind everybody, the very first manufacture of a DCVax-L product for a patient in the Sawston facility, product number 1 ever, was manufactured in February of 2022.
Just two . . . and and there's a press release about it, you can find it on our on our website. . . just two and a half years later, look at where we are. We've completed the phase 1A build out, the phase 1B build out. We have worked with specialized architects and engineers to design the grade C labs, that I'll talk about in a minute, that will be, for the build out going forward. We've gotten, Advent has gotten, all 3 of those licenses, and we're working on commercial readiness, less than two and a half years from the first product ever made GMP in that facility. So that's been a huge area of work. We're very proud of that progress, and it's a, it's a valuable facility.
One of the things we've mentioned, that you may remember from our press release earlier this year, about the progress on the FlaskWorks system, which I'll come to in a second, is that the traditional, type of clean rooms in a GMP, (good manufacturing practice) clinical grade manufacturing facility, are what the Europeans call grade B labs, the letter B as in boy. We would call them class 10, 000 in the US. These are the high level sterility, an entire air change of the whole suite 60 times every hour, I.E. full air change every one minute. Technicians wearing spacesuits, special water, special environmental systems, no particulates, whatever, all of that. Those are the traditional ones. They're super expensive to build. They're super expensive to operate.
What we are transitioning to now, and we're able to do this because of the FlaskWorks system, is we're transitioning to grade C labs, which would roughly be more like class 100, 000 in the US. In other words, it's a lower level of rigor and sterility, and you can only do that when you have your whole manufacturing process is done in a closed way. The word closed is a magic word in the world of medical manufacturing. Right?
When your process is closed, that means it's all kept within a machine, or within a bag, or within a flask, or something that's not open to the air. Because once it's open to the air, it's no longer closed, and then the air has to be basically perfect. And that's very expensive. So the FlaskWorks system has enabled us to transition first to being a closed system for the manufacturing steps, and also to start the process of automation, which is a separate thing and an additional benefit. So we've ,we as we look towards the further development of the Sawston facility, we are, we're moving into to, all grade C labs from here on out.
And another huge difference, just to crystallize it for you . . . In this grade B labs, the more, the more rigorous sterile ones, you can only produce one patient's product at a time. You have to clean the whole suite in between each product. Imagine that. And that's on top of all the special air, and everything that I just said. Okay. And that's because, if you're doing a procedure in there that, at least partially, is open. That's why the word closed is such a magic word. So in the grade C lab, because everything is, magic word . . . closed, you can, the regulators allow you to manufacture product for multiple patients at the same time in the same suite. So you can begin to see the efficiencies. So important.
So that this whole area has been a big amount of focus for us, and work. There's a lot of aspects. It's not simple. Nothing is simple, but it's not simple to change your planning from grade B labs to grade C labs, because not only is the size and the configuration, and so forth, different, even the load on the building is different. And, oddly, some of the load is more problematic, more challenging structurally, for grade C labs, than for grade B labs, which I was surprised about. But, anyway, a lot of work, big area, tremendous progress over the last 18 months.
Just before we leave that subject, in terms of capacity, our current anticipation . . . and this is, you know, based on assessments, by the Advent folks, who are the experts, is that we anticipate that each of the grade C labs should be able to, with two shifts operating, produce about a 1, 000 or 1,100 patients products per year, per grade C lab. Okay? And we anticipate, you know, we're so fortunate this building, is very large, and it's about, close to 88, 000 square feet on 2 floors. We anticipate, ultimately, when the building is fully built out, if it's fully built out with C labs, with our current understanding, and if the engineers don't change things, we anticipate being able to manufacture up to, up to potentially 15,000 patients a year, with all grade C labs in the rest of the building.
So you can start to see, even if we get part of the way towards 15,000 a year, that is an enormous amount of patients, especially for personalized cell therapies. My understanding is, for example, big company, the big companies who bought the CAR T cell technologies, in their first years of commercial operations, made 50 patient products. Right? So, you know, having the eventual capacity to make up to 15,000 patients would be absolutely enormous.
We also have been doing a lot of preparations of the nuts and bolts of things that would be needed for commercial operations. I won't take time on that, but just to give you one glimpse of it, again, giving you flavor. We have established, and it’s existing today, we have controlled clinical grade cryo storage for 3 million vials of doses. So, 3 million is a pretty good amount to start with.
Part of all this is not just the physical aspects of building out the Sawston facility, but there's a step that have, that you have to go through for any medical product for a human patient. And that is, after you manufacture the product, it has to go through product release, and it it has to go through quality control tests, using quality control assays, or tests, or analyses, that have been approved by the regulator. You have to test the sterility, the purity, the potency, the composition, all of that, of your product. Okay?
But you also have to check that all during the manufacturing process, all of those regulatory requirements were met. So you have to check the readouts from the environmental monitoring system to make sure that the the number of particles in the air in the suite, during the entire 7-day process, stayed below the maximum allowed. I mean, it's enormous. And the manual way of doing product release, is for a certified person, they're called a QP, a qualified person, is to manually review all those records.
Well, that can take up to 30 person hours to do that, and that's one thing if a batch of product is like a million tablets. But a batch of product of a personalized therapy, is one patient. So that would have been a bottleneck if you manufacture the product and you can't release it to be used in a patient. So we started, close to 5 years ago now. Advent has worked with a company. They've developed a system, and the system, I won't bore you with the details. We'll have more to say about it, in the coming weeks, and months. But the system essentially automates the product release process, and removes that, as or hopefully, potentially, removes that as a bottleneck. Certainly, greatly improves over the manual process. So, again, huge area of work.
Yeah. I'm taking too much time, so I have to hurry up. Flaskworks . . . I'll just say, 18 months ago, we, they had only developed one approach for the system. It was a good approach. It was attractive. It's part of why we acquired them from Corning, but it wasn't necessarily, specifically as optimized as we would like it to be. So over these 18 months more, we developed two other fundamentally different approaches to the automation, the closing, magic word, and automation of the manufacturing.
Did extensive testing, comparatively evaluated: how did the cells do? Were the cells stressed with one approach or another? Was the yield better? All that kind of thing you would imagine. Selected the best approach, developed, optimized a non-GMP, non-cleanroom version of the machine, and then, went through and, just in this year to date, we've done the adaptation of that, to go into the clean room. Which you have to use different materials, and you have to use some different mechanics and so forth, that I won't go into. So that adaptation work for GMP was recently finished. There are a couple of improvements that we are doing to streamline, and then those units are about to be ordered shortly. So that's the that's the clinical grade machines.
Les is going to, I guess, make a couple comments about the, about the role. Most of this work that I've described has either been carried out, or driven by Advent. So we know that stockholders had some questions about Advent: How our arrangements with Advent are, how we pay them, what the structure is, and Les is gonna give you just a minute or two on that.
Thank you. Advent provides a range of contract services to Northwest that is very important and significant in terms of having people on the ground in the UK able to do things like: manage the complete development of the Sawston facility, prepare for, and draft all the sections of the MAA, from a from a scientific perspective, and the writing on-site, detailed science, oversee the functionality, and the actual work done on the compassionate treatment program, again, all under contract to Northwest. Substantial inputs, as Linda indicated, into development of the Flaskworks system. It involves a lot of collaboration, and a lot of testing and a lot of, it's been amazing how much work has been done, and how great the people there have done on that. And the way that Advent is finishing up ,even right now, things like the restart of DCVax-Direct, which will be coming up, and has done put a lot of work on that in the last 7, 8 months. And and let me take on, and and state how we compensate them under these contracts.
And that is, that the payment structure provides a pass through of all baseline costs, and, a fee, if you will, for the administration of it all, which is a 15% on top of that cost. But Advent doesn't really realize any gain on any of that until they meet the milestones, like getting the MAA in, or or getting the facility going for the next phase of the of the C, the C, services. And so, we find that that kind of an approach is very favorable to us, and to Advent because of the assemblage of all the capability, not only on manufacturing, but on the experimentation, and the work that has to be done on the science side. And so that kind of a compensation is something that allows us to get services that would be far less costly than if we had to go to a third party provider that we didn't have this close intimate relationship with. And and it makes a lot of sense, and it's been a great relationship.
And we monitor all of these inputs very carefully. And, I oversee that. And, we just wanna give you a flavor of how all that works. A large chunk of what we, pay to to Advent is just pass through costs of of the work that they're doing with their personnel and the various contractors that they bring in to do things like get the facility put together, or to do the C labs. Right. Thanks.
Thank you. So we have kind of two more large subjects, to finish up the recap of the last 18 months. Having gone over the MAA, and the facility, and the Flaskworks and all that, Now I like to turn to talking for a minute about intellectual property and collaboration. That's been a a significant area of activity for us.
We've reached completion on some things that we're quite excited about. So I'll talk for, just a minute, a couple minutes about that subject. And then I'll finish by talking briefly about our lawsuit, and the progress of our lawsuit against the parties who we believe are manipulating our stock, and we'd like that to stop. Yeah, so would you, right? Little understatement of the millennium. Right?
Okay. Intellectual property. Let me start with the big picture point. Our goal is to build a franchise in dendritic cell technologies. We want to build a leading, and preferably THE leading franchise in this area. The mainstream thundering herd hasn't yet fully recognized the special capabilities of dendritic cells, but it's starting to happen more and more. If you noticed, for example, when the the federal government created a new agency, modeled on DARPA, the Defense Advanced Research Projects Agency, which they call ARPA-H, for Health, Advanced Research Project.
The very first grant that this elite technologies of the future agency awarded, was a large $25 million grant for Dendritic Cells Technologies, in academic setting. And that's just one glimpse, but increasingly, people are beginning to recognize the special capabilities of dendritic cells. So we are working busily to build a dominant franchise in the meantime, before the thundering herd arrives, or while they're on their way. (haha) So we have quietly, and you may, or may not have noticed, but in our 10K and 10Q’s, we have been quietly reporting that we have been in-licensing technologies that we think will be valuable for the future in building this franchise.
Now just recently, we announced one that was particularly big. I mean, ginormous. And that's the arrangement, the in-licensing package that we did from Roswell Park. But if you noticed, even in that announcement, we explained that that package from Roswell covered 7 years of work by this leading research group on dendritic cell technologies. But we had also completed last year, an in-license of a package of the original older foundational work, that that group had spent 17 years developing, at another institution. And we have in-licensed both of those packages. And we purposely stayed in stealth mode while we put all the pieces together, because we believe, in our own analysis, that the whole, the sum is greater than the parts.
And those two packages together have some just wonderful things in them. They include enhanced versions of dendritic cells. They also include technologies that are complementary to, to use with dendritic cells. For example, a combination treatment regimen, in a trial, or agents to just be immune booster agents, that kind of thing. And if you think about it, interestingly, this collection of new tools or technologies, gives us a lot of growth opportunities, which we can use together with our existing DCVax platforms, which as you know, we have two versions of the platform, DCVax-L for operable tumors, DCVax-Direct that you haven't heard much about recently, but which will be coming up again, now I'm happy to say, for inoperable tumors. We can use these complementary technologies with our own DCVax platforms.
We can even use them with other kinds of agents. You can use a conditioning regimen, for example, that's meant to condition the patient to have more of a response to immune therapies, or is meant to, as people like to say, reprogram the tumor environment, the tumor microenvironment, to be more conducive to an immune response. You can use those with any type of agent. So we could, we could do partnering with other companies who have, biologics, or targeted therapies, or checkpoint inhibitors. That could either be with the dendritic cells included, or with just the other agents.
So we start to have a pipeline that has complementary things, but has many permutations and combinations that we can can do. And, obviously, one of the really nice things about the package, and I was, we were surprised because people, maybe it didn't quite register. But as we said in our announcement, there are two phase 2 trials currently underway with these technologies that we in licensed. Okay? And these two clinical trials are fully funded by grants, and they're being fully carried out by the investigators.
So we don't pay anything, and we don't do anything. But these are the results of technologies that we now have. So those will be going along in the background in parallel, while we're busily working on the MAA, and all of that. And if they produce positive encouraging results, we will then take them on into phase 3. And, we we think Roswell, which is an absolutely top tier. If you don't know, it's a very prestigious institution, very top tier cancer center. We think they've done a marvelous job of developing the technologies at the research stage ,and then the early clinical trial stage, and even now into the mid stage clinical trials.
And we're really gratified that they chose us to pass the baton to, to take it forward, for late stage clinical trial ,and hopefully, eventually, the commercialization. So, these are some of the, intellectual property, but we've been quietly in-licensing quite a number of different pieces of technology that we feel will be useful building blocks in building our, our franchise. And we've also, been putting some collaborations in place. So we haven't announced those yet, but, those will be, something that will be coming along. Okay.
The last section for the past . . . and we went way longer than we're supposed to here . . . is our lawsuit against the seven market makers. You know, all of us, I don't have, I mean I hardly have to say this, but all of us are unbelievably frustrated that the share price is not yet reflecting the value that we are working to build. And we believe that our stock has been manipulated, and we believe that was going on for many years, and we were very anxious to try to take some action to do something about it. But we had to bide our time, and meticulously collect evidence and so forth, because the bar is extremely high. You, the degree of detail that you have to put in a complaint, is, hard to even describe. It’s, I mean, in our, so we did bide our time until we had, what we believe, is a very strong case put together.
We filed that in December of 2022, so just before the last annual meeting, And it has gone through, a whole lot of back and forth skirmishes, all of them relating to the defendant's effort to have the case dismissed, and never go anywhere, by filing a motion to dismiss. And we are very gratified that the magistrate and the court have found that the pleadings in our complaint have been sufficient on all but one of the elements that we have to plead, and that's in process. I'll come back to that. So what they found already, is that our pleadings are sufficient, to pleading that the defendants engaged in manipulation of our stock, and that they did so with scienter, with the intent to damage Northwest. Now, again, we're at the pleading stage.
So the court has only said that we have adequately plead this, but that's a very, very big deal, because these cases that the companies who've been the victims or targets or, never have pretty much not been able to get anywhere trying to seek redress with this kind of case, because you have to be able to articulate all the minute details of the transactions that you allege involve the manipulation. And you have to do that first before you can get to the stage of discovery, but you can't get the information unless you get discovery. So it's kinda like when you get out of school and you can't get your first job until you have experience, but you can't get experience until you have your first job. And so, for years and years, decades, victim companies have have been, unable to get over that bar. And I encourage you guys to read the complaint.
I mean, read it when you wanna go to sleep, but,(haha) I mean, we did our complaint details thousands of transactions down to the millisecond. We're very proud of this, and it, a lot of work went into that. And so, and and we've been vigorously pursuing this case. The only element that the magistrate and the court said that we hadn't plead sufficiently, was one element, which is referred to as loss causation, saying, okay, well, if they did manipulate our stock, and they did have the intention to harm us, you know, what's the connection between their bad behavior, and what damage we say that we incurred.
You have to be able to connect the dots. And there's a time element to it. Like, was it the same day? Was it within 24 hours? Is there a lingering effect that lasts? You know, all of that complexity. So the court, and the magistrate specifically gave us permission to amend our complaint, to strengthen the pleading claims on that one element. We've done that. It's been submitted. The defendants made their objections. We did our reply. So now we're just waiting for the magistrate to evaluate all this, and give their report and recommendation, which then subsequently the court will act, unlike before.
So I know it feels like it's taking a long time, because, you know, it's been a year and a half since we filed a complaint. And we've been fighting, you know, we we try to press the schedule, as much as as we can. But, actually, this is a pretty good pace, from what we understand. It's in line with other cases of this type, and actually a little bit faster even, than some other cases of this type. It's just that the wheels of justice grind slowly, but we are pursuing this vigorously.
So you’ll see that, and there are no guarantees, but we are optimistic about what the ultimate decision will be, about the motion to dismiss. Namely, we are optimistic that it will be denied and the case will be allowed to go forward. We believe our case is meritorious and strong, and we believe that the case may be an opportunity to recoup damages, and to get, what we believe, is manipulation, to stop. So this is a big area of effort for us, and we just want you guys to know that, because we're as frustrated as you, are about the situation.
Okay. That was a really long recap of the last 18 months. The looking forward, I can buzz through faster. Well wanna do, like, a 7th inning, what is that? What inning is it? 7th inning stretch. Anybody wanna do a 7th inning stretch? Get a drink, or whatever, cookie? Just had to check which inning it was. 7th inning stretch. Okay. I know it's way too long . . . .
Was just only meant to be, like, a minute, but, okay. So now we're changing focus to forward looking. And let me remind you what I said at the end of the formal meeting, which is, these are forward looking statements. The actual results could vary materially for lots of different reasons. Please read the risk factors in our SEC filings, and please don't rely on forward looking statements.
So what I'd like to do, is just give you a sense of looking ahead now, for the going forward 18 months or so. What are our priorities that we're gonna be focusing on? And I'm grouping them into 3 groups; our top priorities, our second priorities, and then our, as we can, as feasible, priorities. So I'll give you the 3 groupings, and I'll just, describe. So, needless to say, our top priority, our laser focus, is to complete the process, and hopefully obtain our first commercial approval in the UK, hopefully, approval of the MAA.
We're well underway. We believe the MHRA is following the 150-day process that they have, but we don’t, we do not have confirmation of that. We don't have a way to be sure of that, to know it for sure, but we believe that. It, the “150 days,” quote, unquote, involves approximately 3 stages, and the time frame of each stage is approximate. So it's not, you know, on the button.
The first stage is approximately 80 days of initial review of the application. The second stage is approximately 60-day clock stop, when the agency is going to deliver a list of questions to us, as they do in all these processes. It's not just us. They'll deliver a list of questions. They'll ask for supplementary information, all of that. And, and we will try to respond as fast as we can, which is part of why we're trying to guess what they might might ask, and try to already kind of prepare.
The 3rd stage, which will come after the 60-day clock stop, or however long the clock stop turns out to be, to provide all the answers and info, additional information. The third stage is approximately 70 days of further review, and reaching a decision. Again, the the timelines are approximate. As as far as we've seen, there is not an equivalent thing in the UK that's similar to a PDUFA date in the US. You know, under the legislation in the US, you know, FDA can have a target date for giving you a decision.
We don't have a target date. It'll be what it'll be, okay? And those approximate time frames of those 3 stages that I described, of course, depend also on MHRA's workload, and what backlog they have, and so forth. So that's the approximate process, and the approximate timelines.
I mentioned, with a lot of emphasis, and a lot of discussion about the inspections, that they're gonna inspect everyone, and everything. Those are gonna be going on all during this MAA review process, and those will have to be completed before an MAA decision can be rendered. Right? So there's gonna be extensive inspections, and it's gonna be going on, during this period.
So we, the typical thing, we are gonna follow the typical practice of biotech and pharma companies, which is, we are not going to provide interim step blow by blow. They asked us this, we answered that. They asked us the next thing, we answer that. No, we’re not gonna do the interim steps. We're just going to tell the result when the process is finished. That's the typical approach, and that's the approach that we're gonna be taking. Okay. That's our big priority area, of course.
Another big priority, in this grouping of top priority, is preparations for commercial launch. There, we've been working on this for years, as I've described, but there's still a lot to do. We're very excited about working on this. First off is, we anticipate that we will be beginning commercialization using our existing grade B labs. So we're gonna be pursuing the build out process for the grade C labs as rapidly as we can, but we're not counting on that to get started with commercialization. We're able to get started with our existing B labs. We will, and likewise, we, a part of this preparation for commercialization, will be finishing the process that we described with the FlaskWorks machine.
So now that the adaptation for clinical grade GMP, that design work has been done. The remaining steps are; complete the the streamlining, or condensing some of the portions of it, get the units ordered, have the units delivered, and then Advent will need to conduct a large amount of, what are referred to as, engineering runs. They're practice runs. You have to run, do practice runs with the Flaskworks machine in the Sawston facility, collect all the data, compare the data with the data from the DCVax products produced by the existing manual process, because they have to show, they have to demonstrate to the regulator, not only that the Flaskworks machine operates properly, doesn't shed particles into the clean room air, things like that.
We have to show that it produces a product that's the same, or as close to the same, as a biologic product can be. So they'll be in addition, after they do all of these engineering runs, and they collect all the data, they'll do comparability studies, equivalency studies, and collect the data from that. And then all of that will be submitted to the regulator, and the regulator will give approval. And this will all be going on, these are all things, all going on in parallel. Right? So this will be going on over the coming months, at the same time that the MAA process is going on, and the same time that the inspections are going on, and so forth. So it's not stretching out, you know, to infinity. It's parallel. What else on this? I think that's enough.
We definitely, we need to do some mundane things like expand our operating arrangements. We need to expand our contractual arrangements for leukapheresis, blood draw slots. You have to contract for those, and you have to pay for those. So it's such a little bit of chicken and egg, or a calibration as, you know, you want to have enough slots, but you don't wanna get too far ahead of yourself, and have your burn rate get too high before you need it.
So, anyway, we'll be calibrating, making contract arrangements for more of those slots. We will certainly need to expand the staff who will handle logistics, you know, mundane things like that. There's just a lot of mundane things to do, but it’s, it needs to be done. Among other things is, as part of the preparation for commercialization, we will need to determine what our pricing model is gonna be. What's gonna be the pricing model for DCVAX? That's something on which we will work with expert advisors, and, but it will be important, obviously. And, again, all these tracks going in in parallel. Okay.
After the MAA, and the commercialization preparation, and those activities, we also need to go through the process of applying for approval for reimbursement. So in the UK, that's a process that is handled by NICE. And NICE has been absolutely wonderful to us. I cannot say enough things wonderful about NICE. They've been supportive. They've been flexible. They're standing by.
We talk to them. They reach out to us every couple of months to check on the status of things. I mean, I couldn't imagine a government agency, that's been so supportive as they've been. What we will need to do is, we'll need to engage specialized consultants to develop, what's referred to, as a health economics model. We have to make an economic model about the cost benefits of the DC vaccine treatment, and how it fits with their policies, and that sort of thing. So, that for sure will be, in our grouping of top priority activities, over the, as we look forward, over the coming 18 month period, 12 months, whatever.
Of course we are anxious to submit applications for approval in other countries. We're very happy to be going through our first process in the UK, because they have the fastest process of any that we know of. And it's been really great, but, of course, we want to get start, getting applications put together, and that'll be another thing that we'll be working on during this period, and getting those prepared and submitted. We have a partial head start on them because one big component of the application anywhere, is the clinical study report, which is a ginormous document that has the 20 years of efficacy and safety data from every program that's ever been done in DCVax, even programs other than brain cancer. So, we have a partial head start, but applications in other countries will be important.
And very dear to our hearts, we need to expand the management team. We need to expand the management team rather substantially. As you probably have guessed, and as we described in the proxy, each of the core members of the senior team has been wearing multiple hats, has been fulfilling multiple roles. And I mean, multiple roles that would each be normally a separate senior management person at other companies. And I'm really proud that we've been able to do that, but we need to we need to ramp up. We we've got tremendous opportunity, and we need to ramp up. So that is going to be a significant focus for us, as soon as we can achieve it. We wanna be highly selective, but we plan to substantially expand the management team.
Okay, the last item in our top grouping of top priority, is what I've already mentioned, which is continue to vigorously pursue the lawsuit in New York against the parties, that we believe have been, and are continuing, we believe, to manipulate our stock.
Okay, second grouping of priorities for this going forward period: we plan to initiate the pediatric glioma trial. Just so everybody understands, that conducting the trial itself, is not specifically a requirement connected to our obtaining approval for our adult medicine. What was a requirement, it was in fact a prerequisite, and it was a requirement in order to, for our application to be validated, which it has been as we publicly reported. We had to have an approved plan. We don't have to have completed the trial. So we're going to be pursuing that.
It's been a very long process in the UK. It's been a year and a half of discussions with pediatric neurosurgeons, or oncologists. We actually just recently, finally, after a year and a half of all this, reached conceptual agreement with them. We are gonna be proceeding with just one of the two pediatric trials first, and then the next one will be in sequentially, rather than simultaneous, which is actually a good thing. It'll kind of reduce the bandwidth, and resource requirement on us. So that'll be proceeding.
We, as you can imagine from what I've already discussed, we'll be pursuing build out and equipment of the first grade C lab, the one with the magic closed systems, in the Sawston facility. We will do, on FlaskWorks, what I've already said, which is finish the process. I've already described what that involves.
For the product release system that I described, to release a batch of product, just in terms of where we are with that . . so that was developed from scratch starting about 5 years ago. It was deployed in a pilot version in the small GMP lab in London several years ago. I believe, if I'm remembering correctly, it was about 3 years ago. And it went through a pilot testing period in the small GMP lab in the London facility. And then I believe about a year ago, if I'm remembering correctly, was, initially, it was installed on a pilot basis, in Sawston.
And now we have to go through all the usual steps. We have to go through the practice runs, it has to be optimized, we have to collect data, and so on. And we always have to show equivalency. Right? We have to show that the system produces an equivalent evaluation as the manual process by a QP, a qualified person. And again, this is another parallel track. This isn't, you know, off, you know, in the future, it'll be in parallel underway. Advent will be doing all of this, so fortunately, won't be us.
DCVax-Direct . . . very near and dear to our hearts. We have been eager to restart this program for a long time. And we, the first thing, of course, that we need to do, is restart the manufacturing. As it turns out . . . and this will be something that we'll make a public announcement when the time is right . . . anytime that you do a technology transfer process, because that product was only ever produced in the US, by parties who are no longer there, and so we had to do a technology transfer process to the Sawston facility.
Whenever you do a technology transfer process, you have to draft a whole new set of SOPs, (standard operating procedures), regulatory documents, all of that. And usually a technology transfer, especially for a cell therapy, is a minimum of at least 6 months of work. And then we've had two additional, challenges, which I think, we're on our way to having behind us. One that related to the machine that we use for the first stage of the process, and one which related to some key ingredients in the process. And when we come to that announcement, we'll we'll sort of explain all that.
But suffice it to say, restarting the manufacturing process, is a significant priority for us, in this going forward period, and you'll be hearing from us about that. And then once we've got the manufacturing restarted okay. Then we come to the last grouping of priorities. Once we have the manufacturing restarted, we are very eager to get the clinical trials underway to proceed. I guess, I don't know to what extent people remember, but the early stage trial that we did, was a phase 1 trial which, in which, it was conducted at MD Anderson.
We treated 13 different types of solid tumors, very diverse, pancreatic, breast, sarcoma, lung, colorectal. I mean, very diverse solid tumors, with very encouraging survival extensions in patients who were metastatic, and had failed every other treatment, and were pretty, pretty broken. DCVax-Direct. So that was really encouraging in the phase 1 trial. And even today, with all the billions that have been spent by the whole pharma and biotech industry on cancer treatments, when you have metastatic solid tumors today, there's not very much for you, as a patient.
And DCVax-Direct is a wonderful technology because it's directly injected into the tumor. The tumor that can't be surgically removed, either because there's too many of the tumors, or because it's located somewhere, where you might bleed out on the operating table, whatever, that are inoperable. But you, with image guidance, any form of image guidance, physician's choice, you can reach pretty much any location in the patient's body, to inject directly into the tumor. And even now, all these years later, we haven't seen, I'm not aware . . . maybe it's out there, but I'm not aware, we aren't aware . . . of any treatment like it, that's had the kind of encouraging results that the phase 1 trial did, and MD Anderson, in these patients. So we are very eager to get, get going again with that program. So that is, another priority.
We also, we have said, in all of our presentations about the results of our . . . now switching back to DCVax-L, lysate, for tumors that are operable . . . we have said, in all of our public presentations about the trial results, that this is very exciting to see the survival extensions with DCVax-L by itself, as a monotherapy, and version 1.0 of the DCVax-L technology, and that we are eager to build on that, with combinations of DCVAX L. And because DCVax-L has such a benign safety profile and because of what its mechanism of action, as a broad spectrum, we believe, that it will be eminently combinable with most other types of treatments.
You can imagine combining it with checkpoint inhibitor drugs, with targeted therapies, with chemotherapies, any variety of type of therapy. So we, we have some collaboration discussions underway, and at the appropriate time, because we only announce things when they're significant, and they're done. Right? We don't say, and that you know, giving our forward perspective, is quite unusual for us. But, anyway, again, these are forward looking statements. Everybody knows that. Right? Just reminding you again.
But we have said in every presentation, we are eager to combine DCVax-L with these other combinations. And so one of our many priorities, for the going forward period, is to do one or more of those combinations. And we've received considerable interest from various parties for that. So, we are looking forward to that. One thing I will say about our general approach, as we look forward on further clinical trials, is this: We want to focus particularly on clinical trials where tumor response, meaning tumor shrinkage, can be the endpoint as opposed to overall survival being the endpoint.
Why? Because, if you're going to see tumor shrinkage from a treatment, you can typically, potentially see it in a matter of months . . . and survival takes years and years. And we've just got done conducting one of the biggest, one of the longest, one of, you know, a real a major landmark in the field, in our opinion. But we would now like to do some more focused, faster path, tumor shrinkage endpoint trials. So we are, as we evaluate, I mean, we have so many opportunities in front of us now. Really, the challenge is choosing. Right? And so we we gotta steer ourselves, to the extent we can, towards that direction, to more shrinkage endpoints.
Two last points before we're done, done, done. Partnering. We've had some questions, various questions from shareholders. We're quite open to partnering. I've just I gave you a couple examples earlier of potential partnering, especially now that we have this tool chest of all these more technologies. But we're open to partnering. We'd like to be, where we see a partnering that could have either strategic value, or financial value, or both. And as we think about it, a partnering could be a regional partnering, geographic region. We have made a point of filing our IP and maintaining our IP in countries, wide range of countries. And we we try to build for the day when it would be, useful for that type of partnering, or it could be partnering for particular applications. So, we ,we will be open to that, and see what makes sense.
Last but not least, some folks have asked about uplisting. Certainly, everyone would love to be on a national exchange rather than the OTC, and we do realize, we do know that you guys are having difficulties, some of you, with the brokers, and they're making it difficult sometimes with our shares, while we're on the OTC. So we, we will be looking for when the strategic timing is right. We're not quite there yet, but we will be looking for that, so as we look at the going forward, period.
So let me close with just, a couple of concluding comments. First of all, I've I've tried to give you a flavor of a lot of different areas, without being here till next Tuesday. It's been longer than it was supposed to be. But all in all, I I have to say we've made, we feel, we've made tremendous progress in the last 18 months.
We're such a different company, further on company, than we were 18 months ago, and we're proud of that. And we hope that you are finding that exciting too. Second, comment is; there's no guarantees. I have to say this again, but we believe that we are well positioned to get a favorable result, and get our first approval, and begin commercialization. So that's all we can say is, we believe that we're well positioned, but, you know, and we'll all know, you know, reasonably soon.
We also believe that the infrastructure, and the systems that I've tried to give you a glimpse of without being too boring, that we've been working on these for years, in order to build for the day that's now arriving. Show that we have the physical facilities, and we also have the operating systems, and the strategies that can make this kind of a product, you know, can facilitate the commercialization. Also, we believe that at this point, with the careful in licensing, we've built a tool chest that has just tremendous growth opportunities to work with. I'll say again, we are painfully aware that the share price does not, at least currently, not yet, reflect this progress that we've made, that I'm describing. And I've said several times now repeatedly, we know how frustrating that is.
I will say, we believe, that if we can continue making progress in building actual value, intrinsic value, real value, and if we can continue taking action against parties, that we believe are artificially manipulating, and holding the shares down, and if we can work to attract some additional institutional investors, like our recent one, that we're very gratified, we think the combination of those things, building intrinsic value, fighting back against what we believe is manipulation, and attracting institutional investors, that ultimately the market will recognize the value. We know that we're not there yet.
And last of all, is what I get began with, which is we're so appreciative of all the votes that you guys cast. It was a phenomenal turnout, really impressive turnout, and we're so grateful for all the positive votes. And thank you. We're all done. I move that the meeting be adjourned.
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Expert Financial Analysis and Reporting
Northwest Biotherapeutics: CEO Linda Powers’ In-depth Company Overview at the Annual Meeting
POSTED by LARRY SMITH on JUL 8, 2024 • (0)
Glossary of Key Acronyms Used in this Report
MHRA Medicines and Healthcare products Regulatory Agency is the United Kingdom regulatory counterpart to FDA. The two agencies have a close, collegial working relationship. Approval of DCVax-L by MHRA would carry great weight in the FDA’s decision making.
MAA Marketing Authorization Application is the document that must be submitted to the MHRA by companies seeking approval for a drug. The MIA is an integral part of this submission. Approval of the MAA allows commercialization.
MIA Manufacturer's Importation Authorization is required by the MHRA before a company can manufacture, import or export drugs. To qualify, a manufacturer needs to demonstrate to MHRA that it complies with good manufacturing practices and can pass regular GMP inspections of its manufacturing site.
GMP Good Manufacturing Practice is a system required by regulatory agencies for ensuring that drugs are consistently manufactured according to carefully defined quality standards. Guidelines address issues such as process validation, quality assurance assays, record keeping, personnel qualifications, sanitation, cleanliness, equipment verification and others.
NICE National Institute for Clinical Excellence plays a crucial role in determining reimbursement for new pharmaceutical products and treatments in the UK's National Health Service (NHS). It is considered to be the gatekeeper to reimbursement by the NHS. A positive recommendation from NICE typically obliges the NHS to make funding available for a product or treatment, usually within three months
Introduction
It has been over a year since CEO Linda Powers has spoken about her strategic vision for Northwest Biotherapeutics; during this time there has been some remarkable progress. At the annual shareholder meeting on June 29th, 2024 CEO Powers provided a comprehensive, hour long overview of what has been accomplished over the last 18 months and her key priorities for the coming year. In this report I have largely reproduced a verbatim transcript of her talk which contains a wealth of information. I have summarized what I consider to be the key points, but I would urge you to read the whole report in order to understand the amazing job that NWBO has done with the development of DCVax-L in the face of an egregious stock manipulation scheme that has had an extremely negative impact on the stock price and blocked ready access to capital.
The transcript of her talk is over 18 pages. Speaking is not always as precise as writing which makes reading the transcript challenging. I have tried to edit and organize the subject matter to give a more user friendly format. My purpose is to organize and edit but not to inject my own thoughts. Her presentation focused on issues relating to:
MAA submission for DCVax-L in the UK,
Manufacturing accomplishments at Sawston with special emphasis on Flask Works,
Broad, industry leading portfolio of intellectual property covering dendritic cell technology that has been assembled.
Groundbreaking lawsuit against the market makers who have been manipulating the stock price and continue to do so,
Key accomplishments in the past 18 months and
Priorities for the coming year.
My Key Takeaways
I would urge you to take the time to read this full report. However, if you just want a quick summary here are my key takeaways.
The MHRA is actively reviewing the MAA for DCVax-L for the treatment of newly diagnosed and recurrent glioblastoma multiforme (GBM). The regulatory agency has not issued and will not issue guidance on when their review process will be completed. Most analysts who closely cover the company, me included, are estimating UK approval in the September-October of 2024 time frame.
NWBO has done an awesome job in building a world class personal cell manufacturing capability at its Sawston, UK facility to support the commercial launch. MIA approval was obtained in March 2023.
Before launching DCVax-L in the UK, NWBO will need to get a favorable reimbursement recommendation from NICE. Ms. Powers reported that there have been ongoing interactions with NICE over years that have been quite encouraging and there is reason to hope that a positive reimbursement recommendation will follow swiftly on the approval of the MAA.
The manufacturing capacity at launch is expected to be 1,000+ patients per year using grade B clean labs. However, the implementation of the Flask Works grade C lab technology could expand capacity to 15,000 in the not too distant future.
NWBO has assembled an industry leading, dominant package of intellectual property covering dendritic cell technology which was recently bolstered substantially by the acquisition of a very important IP package from Roswell Park whose scientists have spent 24 years developing a cutting edge dendritic cell technologies and arguably are the leading group worldwide in this field.
Along with the IP acquired from Roswell, NWBO also gained control of two phase 2 trials that are being conducted by independent investigators that are fully funded by grants. NWBO will not be required to fund these trials or to provide any support until a phase 3 begins (if warranted). This gives an immediate jump start to the medium term pipeline.
NWBO has been the target of a long term stock manipulation scheme that has had a devastating impact on the stock price. The company filed a lawsuit against seven market makers in December 2022 to block this. I believe that the defendants motion to dismiss the lawsuit will be denied in a month or two and allow NWBO to go forward to discovery. This could lead to stopping the manipulation and ultimately the awarding of substantial damages, possibly meaningfully above $1 billion.
Discussions are underway to begin combination trials of DCVax-L with other drugs such as checkpoint inhibitors, targeted therapies and chemotherapies. We may hear more by year end. Phase 2 trials of DCVax-L combined with checkpoint inhibitors and other drugs have produced very exciting results in GBM.
The company is in a number of discussions involving partnering parts of its technology platform. We may hear more by year end.
NWBO is in the process of restarting trials of DCVax Direct. This product takes a different approach from DCVax-L in that it addresses the treatment of metastatic cancers in which the tumor cannot be surgically removed. This is a huge unmet need. DCVax-L addresses cancers that are surgically resectable.
The major weakness of NWBO is an extremely strained balance sheet. Approval of the MAA and denial of the motion to dismiss in the lawsuit could provide access to the substantial low cost capital needed to implement the Company’s plans. Ms. Powers did not directly address this in her remarks.
The company chose to file for regulatory approval in the UK because the process is much faster than for other regulatory agencies and because it us highly respected will carry great weight in future decisions by other regulatory agencies. It is preparing to file for approval in the US, European Union and elsewhere following UK approval.
The MAA Submission to the MHRA
Prerequisites to Filing the MAA
The MAA was filed on December 20, 2023 seeking approval for both newly diagnosed and recurrent glioblastoma multiforme. In addition to the clinical trial results from the DCVax-L phase three trial, there were significant prerequisites that had to be completed before MHRA would accept the submission.
On March 20, 2023 NWBO announced that an MIA license had been approved and issued by the MHRA for commercial manufacturing of cell therapy products at the GMP facility in Sawston, U.K. Under this license, cell therapy products manufactured in the Sawston facility may be exported globally. Products (e.g., immune cells) may also be imported into the U.K. for production or release of cell therapy products under the facility’s licenses. This license was obtained by Advent
A human tissue authority license is a regulatory requirement for organizations that use and store human tissue. This was also obtained by Advent.
A Pediatric Investigation Plan (PIP) for clinical trials of DCVax-L in children had to be submitted to and approved by the MHRA; beginning the trial is not a requirement for approval of the MAA for DCVax-L. This work was largely done by NWBO.
Ms. Powers said that the interactions with MHRA have so far been wonderful. They gave NWBO quicker than expected turnarounds on each of these prerequisites.
Trial Master File Submitted with the MAA Is an Enormous Document
This phase three trial was one of the largest clinical trials of a cell therapy product (particularly a personalized cell therapy product) that has ever been conducted. This resulted in an enormous Trial Master File (TMF) which is a comprehensive collection of documents that provide evidence of how a clinical trial was conducted and managed. It also contains essential documents that demonstrate compliance with regulatory requirements and Good Clinical Practice. It allows monitors, auditors, and regulators to evaluate the conduct of a trial and the quality of data produced.
Pulling together all of the contents of the TMF, was an enormous organizational exercise. The drafting in combination with medical writers began in the fall of 2022. If the digital file were reproduced on paper, it would create a stack of paper 200 feet tall. There cannot be any gaps in the file and all data must be easily accessible. For example, if inspectors want to see lab tests for patient X at clinical trial site Y, the regulator must be able to immediately access that data.
Preparing for MHRA Inspections as Part of the MAA Review
An enormous amount of work is required to prepare for MHRA field inspections. NWBO as the sponsor is going to be inspected as are the contract research organization that conducted the trial, the independent database company that held the database and certain hospital trial sites. Each organization has to have everything ship shape and NWBO has been working diligently with teams of consultants to prepare them. MHRA typically sends a team of inspectors who may stay for a week or more. NWBO hired people who previously worked as inspectors for regulatory agencies and now act as consultants, to conduct audits and mock inspections. They try to anticipate what kind of questions MHRA will ask and what kind of supporting information might be required.
Demonstrating Mechanism of Action
The MHRA will also have questions on the proposed mechanism of action of DCVax-L. Over the last 18 months, NWBO completed and then presented results from mechanism of action studies which studied the underlying biology of how DCVax-L is believed to work. Chief Technical Officer, Dr. Marnix Bosch, presented that information in a company presentation at ASCO last year. It is tremendously important because it strongly supports the underlying biology hypothesized for DCVax that results in its broad spectrum of activity.
It was shown that the dendritic cells on which DCVax-L is based are picking up a very broad range antigens from the tumor tissue sample (the lysate). Studies showed that over 600 different tumor antigen targets were displayed to T-cells. This is the basis for its broad spectrum of activity. Those studies were extremely important to add scientific underpinning that supports the clinical trial results that have been seen. Proteomics technologies that study the activity of proteins that have only recently been developed and were used in this study.
Data from the Compassionate Use Program Supplements the MAA
They continue to follow patients still alive from the phase 3 trial; the exact number wasn’t specified. With standard of care, the five year survival rate is about 5%. There are still a meaningful number of patients alive from the trial in which the last patient was enrolled in November of 2015. This means that each of these patients has survived at the very least about nine years. NWBO has gleaned important information about these long-term survivors.
There has been a long running, well over a decade, compassionate use program that has provided valuable, real world experience. In a clinical trial, the goal is to replicate in cookie cutter fashion the treatment of each patient. However, this is not how it works in the real world. For example, there are patients whose tumor tissue sample wasn't in the condition that it was supposed to be. It may not have been frozen quite the right way or was frozen several years ago or the patients were way outside the age range. They have had patients in their 80s. And so the compassionate use program has been valuable in gaining a tremendous amount of real world experience, basically practicing for what will happen when they go commercial. Recent activity has slowed because of the preoccupation with the MAA.
Activities At Sawston, Commercial Preparation and Flask Works
Sawston Has Received a License for Commercial Production of DCVax-L
Another huge area of activity over the past 18 months has been in the development of the Sawston facility allowing for the MIA and TIA licenses. To put this in perspective, Ms. Powers provided some history. The very first manufacture of DC-VAX-L for a patient in Sawston was in February of 2022. GMP allowing for the MIA in Sawston was obtained less than two and a half years from the time this first product was made; there has been enormous progress. Phase 1 grade A and grade B lab build outs that will be used for initial commercial production which were the basis for the MIA approval. Specialized architects and engineers are at work to design the grade C labs under development with Flask Works technology that will be ultimately used in production. Advent is working on commercial readiness.
Grade B Labs Will Be the Basis for Initial Manufacturing, But Grade C Labs Based on Flask Works Are the Future
NWBO highlighted in a March 2024 press release progress made in the Flask Works system which ultimately will be used for all production at Sawston. Before discussing Flask Works, Ms. Powers addressed the traditional type of clean rooms involved in a GMP (good manufacturing practice), clinical grade manufacturing facility. The regulatory requirement is to have labs with no particulates in the air. Europeans call these grade B labs; in the US they are referred to as a class 10,000 lab. They are high level sterility facilities that perform a complete air change of the whole suite once every minute. They are manned by technicians wearing spacesuits. Facilities require special water and environmental systems.
The traditional Class B facilities must be perfectly sterile and are very expensive. The objective of Flask Works system is to enable NWBO to transition first to being a closed system for most manufacturing steps and then to automate the process in a grade C lab which will ultimately be the basis for all commercial manufacturing at Sawston.
Manufacturing Capacity Will Be Significantly Increased in a Grade C Lab
In the most rigorous, sterile grade B labs, only one product for one patient can be produced at a time. Then the whole suite has to be cleaned before the next product can be produced because the procedure is partially open. In the grade C lab, everything is closed allowing for the manufacture of product for multiple patients at the same time in the same suite. This has been a huge focus for NWBO. It's not simple to change planning from grade B labs to grade C labs, because not only is the size and the configuration different, even the load on the building is different. There has been tremendous progress over the last 18 months.
In terms of initial capacity, the current anticipation for the class B lab is estimated to be about 1,000 or 1,100 DCVax-L patient treatments per year. Sawston is very large with close to 88,000 square feet on two floors. When the building is fully built out with C labs, it is anticipated that each of the grade C labs operating with two shifts should be able to provide product for 15,000 patients a year. That is an enormous amount, especially for personalized cell therapies. The big companies who brought the CAR T cell technologies to the market in their first years of commercial operations were only able to produce 50 patient treatments per year. Having the eventual capacity to make product for up to 15,000 patients would be an absolutely enormous manufacturing achievement.
Additional Nuts and Bolt Preparations for Commercialization
There have also have been a lot of preparations for the more nuts and bolts things that are needed for commercial operations beyond the physical aspects of building out the facility. One example is that NWBO has established controlled clinical-grade cryogenic storage for three million dosage vials. Also, readouts from the environmental monitoring system must be able to make sure that the number of particles in the air in the suite during the entire seven-day process stays below the maximum allowed.
An important focus is that after manufacturing is completed the product has to go through product release. This requires quality control tests using assays or tests or analyses that have been approved by the MHRA to test and assure the sterility, purity, potency and composition of the product. These are regulatory requirements.
The manual way of doing product release is for a certified quality person (QP) to manually review all records which can take up to 30 person hours. It’s one thing if a batch of product is made up a million tablets, but entirely different if a batch is a personalized therapy for one patient. The development of the manufacturing process was started five years ago by their Advent. It essentially automates the product release process and removes it as a bottleneck.
More on Flask Works
Before the acquisition by NWBO, Flask Works had developed only one approach for its system. It was a good approach and part of the reason why NWBO acquired it from Corning. Still, it wasn't as optimized as NWBO wanted. So over the last 18 months since the acquisition, Advent and NWBO have developed two additional, fundamentally different approaches to the automation and the closing of the manufacturing process. Extensive comparative testing between the two evaluated how cells did with one approach or another looking at parameters such as the yield and the stress on the cells.
They first developed an optimized non-GMP, non-clean room version of the machine and then adapted it for the clean room. This required the use of different materials and different mechanics. The adaptation work for GMP was recently finished. There are a couple of improvements that are being done to streamline the machine for which units are about to be ordered.
Advent’s Contributions Have Been Critical
Most of the work at Sawston has been carried out by Advent which provides a range of contract services to Northwest that are critical. Advent people on the ground in the UK do things like:
Manage the operation and development of this Sawston facility,
Draft all the manufacturing related sections of the MAA,
Conduct on-site detailed science,
Oversee the functionality and the actual work done on the Compassionate Treatment Program.
This is all done under contract and in collaboration with NWBO.
Advent is owned by the Toucan Investment Fund which is managed by Linda Powers and this makes it a related entity. Working with Advent is far less costly than would be the case if NWBO were using a third-party provider with whom it did not have a close relationship. It makes a lot of operational sense and has produced a great working relationship.
NWBO monitors Advent inputs and costs very carefully. A large chunk of what is paid to Advent is just pass-through for costs of the work that they're doing with their personnel and the various contractors that they bring in to work on Sawston. Advent is compensated with a pass-through of costs plus a 15% fee on top. Payment is based on meeting contractual milestones, e.g. receiving the MAA or getting the facility going for the next phase of designing the grade C lab. Advent is extremely valuable to NWBO not only in its manufacturing capabilities, but also on experimentation and the work that has to be done on the science side.
NWBO Has Assembled an Industry Leading Portfolio of Intellectual Property
Dendritic Cell Technology Is in Its Early Stages of Development
Acquisition of dendritic cell technology intellectual property has been a significant area of activity and has been very productive. From a big picture standpoint, the goal is to build a to build the industry leading platform. The mainstream biopharma thundering herd are always a followers on innovative technologies such as monoclonal antibodies and CAR-T.
The herd hasn't yet fully recognized the special capabilities of dendritic cells, but it's beginning. For example, when the federal government created a new agency modeled on DARPA (Defense Advanced Research Projects Agency) which is called ARPA-H (Advanced Research Projects Agency for Health). The very first grant that this elite “technologies of the future” agency awarded was a large $25 million grant for dendritic cell technologies to an academic setting. Increasingly people are beginning to recognize the special capabilities of dendritic cells. NWBO has been aggressively building a dominant franchise before the thundering herd recognizes the promise of dendritic cell technologies.
In its regulatory filings, NWBO has been quietly reporting on the in-licensing of technologies that they believe will be valuable in building this franchise. NWBO just recently announced a consequential agreement that was the in-licensing of IP from Roswell Park Comprehensive Cancer Center. It covered the IP package developed by a world leading group of dendritic cell scientists based on seven years of work at Roswell. However, NWBO previously completed an in-license of a package of the original, older foundational work which that group had spent 17 years developing at another institution.
Synergy of Acquired Intellectual Property and Technologies with the DCVax Platform
NWBO stayed in stealth mode while it was putting all the IP pieces together. The two packages just described have some wonderful things in them. They include enhanced versions of dendritic cells. They also include technologies that are complementary to use with dendritic cells such as immune system boosters for use in combination trials. This collection of new tools and technologies provides a wealth of growth opportunities that complement the existing DCVax platform of which there are two versions. DCVax-L is for operable tumors and DCVax Direct for inoperable tumors. NWBO hasn’t said much about DCVax Direct lately, but Advent is finishing up requirements that will allow a restart of the DCVax Direct program
The in-licensed IP also can be used with drugs of other companies. For example, there is a conditioning regimen meant to condition the patient to have a stronger response to immune therapies; this is referred to as reprograming the tumor microenvironment. This is synergistic with any type of agent and would allow NWBO to partner with companies who have biologics or targeted therapies or checkpoint inhibitors which might or might not be promising combinations with the DCVax platforms.
One of the really important aspects of the in-licensed package from Roswell is that NWBO gained two phase two trials currently underway. They are fully funded by grants and are being fully carried out by independent investigators. NWBO isn’t required to provide funding or any other type of support. If they produce encouraging results, NWBO will then have the right to take them into phase three. Roswell is a very prestigious, top tier cancer center. They have done a marvelous job of developing dendritic cell technologies at the research stage and at the early clinical trial stage and even now into the mid stage clinical trials. NWBO is really gratified that they were chosen to carry the baton to take these assets forward into late stage clinical trials and hopefully into commercialization.
These are some of the intellectual property, that NWBO has been quietly in-licensing. They provide quite a number of different pieces of technology that they feel will be useful building blocks. NWBO has also been putting some collaborations in place which haven’t yet been announced; those will be something that will be coming along.
Lawsuit Against Citadel, Virtu, Canaccord Genuity, G1 Execution, GTS, Instinet and Lime Trading-in the United States District Court, Southern District of New York.
Status of the Lawsuit
NWBO filed a lawsuit in December 2022 that alleges that seven market makers illegally manipulated its stock price. Management and investors are unbelievably frustrated that the share price is not reflecting the value that has been and is being built because of this. NWBO believes this scheme has been going on for many years. Management was very anxious to try to take some action to do something about it, but had to bide its time and meticulously collect evidence as the bar for success in this type of lawsuit is extremely high. The degree of detail required to be put in a complaint is hard to even describe. NWBO did bide its time until it could put together a very strong case.
Since the lawsuit was filed, it has gone through a lot of back and forth skirmishes, all of them relating to the defendants’ effort to have the case dismissed by filing a motion to dismiss. NWBO is encouraged that the magistrate and the court have found that the pleadings in the complaint have been sufficient on all but one of the elements that they need to plead in order to deny the motion to dismiss and proceed to discovery and then to trial or settlement.
NWBO Has Successfully Pled that the Market Makers Purposely Manipulated Its Stock
The magistrate and district court have found already that NWBO’s pleadings are sufficient to show that the defendants engaged in manipulation of the stock through spoofing and that they did so with scienter (intent to damage Northwest). This is at the pleading stage so the court has only said that they have adequately pled this; it has to be proven in a trial. However, this is a very, very big deal. This is a widespread scheme and there are many, many cases in which the companies who've been the victims or targets of this alleged criminal enterprise have not been able to get anywhere close to trying to seek redress.
This is because the plaintiff must articulate all the minute details of the transactions that are alleged in the manipulation before getting to discovery. However this data is controlled by the market makers and DTCC and not readily available. This is a catch 22 in which the data that is necessary to proceed to discovery isn’t available unless they get to discovery. Hence for years and years, victim companies have been unable to get over that bar. Ms. Powers encourages investors to read the complaint in which the result of a special investigative technique allowed them to get details for thousands of transactions down to the millisecond. NWBO is very proud of this and a lot of work thar went into it over the years that NWBO has been vigorously pursuing this case.
The Court found based on NWBO pleadings that the market maker defendants had spoofed the stock. Spoofing is a trading strategy where traders manipulate market prices by pretending to have interest in buying or selling assets without the intention to execute those trades. In the U.S., spoofing was explicitly made illegal by the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010. In addition to spoofing, NWBO had to demonstrate three other acts in its pleading. Two of these were reliance which essentially means that the trading data used in the pleading is valid and scienter which means that the defendants knowingly spoofed the stock with the intent to damage NWBO. The magistrate ruled in NWBO’s favor on reliance and scienter as well as spoofing.
Successfully Pleading Loss Causation is Key to Having the Motion to Dismiss Denied
The fourth and final element of the case is loss causation. This must establish that the illegal spoofing did cause financial damage to NWBO. It needs to be shown that that there is a connection between the defendants bad behavior and the damage it caused. The magistrate and the court said that NWBO hadn't pled sufficiently this element which is referred to as loss causation. The court was asking if they did manipulate the stock with the intention to harm, in what time frame and to what extent did this occur? Was it the same day? Was it within 24 hours? Was there a lingering effect that lasts for much longer-weeks, months or years? Encouragingly, the court and the magistrate specifically gave NWBO permission to amend its complaint to strengthen the pleading claims on loss causation.
An amended filing that only deals with loss causation has been submitted. There is no need to reargue reliance, spoofing or scienter. The defendants made their objections to the filing as it pertains to loss causation and NWBO replied. The company is now waiting for the magistrate to evaluate this and give his report and recommendation, which the court will then act on. It has been a long time ( a year and a half) since the complaint was filed. They have tried to press the schedule as much as they can but defendants went to great lengths to slow the process. Still, this is a pretty good pace from what they understand. It's in line with other cases of this type and may actually be a little bit faster. It's just that the wheels of justice grind slowly.
Strong Reasons to Believe Defendants Motion to Dismiss Will Be Denied
There are no guarantees, but they are optimistic about what the ultimate decision will be about the motion to dismiss, namely, that the motion to dismiss will be denied and the case will be allowed to go forward to discovery. They believe the case is meritorious and strong and that there will be an opportunity to recoup damages and to get the manipulation to stop.
Looking Forward
To this point, the presentation focused on accomplishments reached in the last 18 months. The next part of the presentation dealt potential milestones upcoming in the 18 months or so. CEO Powers laid out priorities, grouping them into three categories: top priorities, second priorities and then feasible priorities.
Top Tier Priorities
MAA Approval for DCVax-L in the UK
Needless to say the top priority on which they are laser focused is to complete the process and hopefully obtain the first commercial approval of DCVax-L in the UK. NWBO believes that the MHRA is following the hundred and fifty day process that they have but do not have confirmation and don't have a way to be sure. They believe that the hundred and fifty day process involves approximately three stages and the time frame of each stage is approximate. The first stage is approximately 80 days of initial review of the application. The second is approximately a 60 day clock stop when the agency delivers a list of questions to the sponsoring company. It's not just that they deliver questions; they may also ask for supplementary information. After the 60 days or however long the clock stop turns out to be, there is a third stage of approximately 70 days in which MHRA may seek additional information. NWBO is trying to guess what they might ask and to prepare to provide all the answers and for additional information the third stage.
In the US, the FDA gives a target date for reaching a decision. There is not an equivalent thing in the UK. The approximate timeframes of the three stages also depend also on MHRA's workload and backlog. CEO Powers also emphasized that during this approximate 150 day process there will be numerous inspections that will have to be completed before an MAA decision can be rendered. NWBO as is typical for biopharma companies will not provide information on interim steps or questions asked and answered. They will just release the result when the MAA reaches its decision.
Preparing for the Commercial Launch
Another top priority is preparation for commercial launch. They have been working on this for years, but there is still a lot to do. They anticipate beginning commercialization using the existing grade B labs while pursuing . the buildout process for the grade C labs. As a part of this preparation for commercialization, they will be finishing the process previously described for the Flask Works machine to establish a grade C lab. The design work has been done. Advent will need to conduct a large number of engineering or practice runs. They will need to collect all the data and compare it with the data from the DCVax-L products produced by the existing manual process.
NWBO will have to demonstrate to regulators that the Flask Works machine operates properly and doesn’t shed particles into the clean room air. They also have to show that it produces a product that's the same or acceptably close to the same. They will collect all the data and do equivalency studies and collect the data from that. These will be submitted to the regulator for approval.
These are all things going on in parallel as the MAA process and inspections are taking place. They also need to do some more mundane things like expanding operating arrangements. One example is expanding contractual arrangements for leukapheresis blood draw slots. They have to contract for those and they have to pay for them so it's such a little bit of chicken and egg calibration. They want to have enough slots but don't want to get too far ahead of needs and needlessly increase the burn rate. So they will be calibrating contract arrangements for more of those slots. They will certainly need to expand the staff who will handle logistics. As part of the preparation for commercialization, they will need to determine what the pricing model is going to be for DCVax-L. That's something on which they are working with expert advisors and it will be important obviously and again all these tracks are going in in parallel.
Applying for Reimbursement
Following MAA approval, they will need to go through the process of applying for reimbursement. In the UK, gatekeeper is NICE. CEO Powers says that NICE has been absolutely supportive in their dealings with NWBO and she cannot say enough wonderful things about the relationship so far. They have been reaching out to NWBO every couple of months to check on the status of things. She couldn't imagine a government agency that's been as supportive of as they have been. NWBO will need to do a health economics model that justifies the cost benefits of the DCVax-L treatment.
NWBO has engaged specialized consultants to develop that model. This is certainly one of top priorities over the coming 18 month period.
Filing for Approval in Other Countries
NWBO is planning to submit applications for approval in other countries. They are very happy to be going through the first approval process in the UK because they have a very fast process; probably the fastest in the world. In submissions to other counties, they have an important head start because one big components of the application anywhere is data comparable to the trial master file combined with the 20 years of efficacy and safety data from every program that's ever been done with DCVax-L This includes use with cancers other than GBM.
Expanding the Management Team
The management team needs to be substantially expanded. Core members of the senior team have been wearing multiple hats fulfilling multiple roles. In many cases these normally would require a separate senior management person. They need to ramp up, but want to be highly selective as they expand the management team.
Vigorously Pursuing the Lawsuit
The last item in the grouping of top priority is to continue to vigorously pursue the lawsuit in New York against the parties that we believe have been and are continuing to manipulate our stock.
Second Grouping of Priorities
Pediatric Trial of DCVax-L in the UK
NWBO is planning to initiate a pediatric glioma trial with DCVax-L in the UK as a requirement by MHRA. CEO Powers emphasized that completing the trial itself is not a specific requirement for obtaining approval for the adult GBM indication. What was in fact a prerequisite in order to file the MAA was that they had approved plan. This was a long process in the UK that involved a year and a half of discussions with pediatric neurosurgeons and oncologists passing before reaching conceptual agreement. NWBO is going to proceed with just one of the two planned pediatric trials first and the second one will be sequential rather than simultaneous. This is actually a good thing as it will reduce the bandwidth and resource requirement.
Restarting the DCVax Direct Program
NWBO has been eager to restart the DCVax Direct program. The first requirement is to restart manufacturing which requires a technology transfer to Sawston. This is necessary because the product was only produced in the US by parties who are no longer operational. This requires the drafting of a whole new set of standard operating procedure, regulatory documents.
Usually a technology transfer especially for a cell therapy is a minimum of at least six months of work. There have been two major challenges that have been faced and hopefully will soon be behind NWBO. One related to the machine that is used for the first stage of the process and the other to some key ingredients in the process. Restarting the manufacturing process is a significant priority. There will be a press release once manufacturing is restarted
Once manufacturing is restarted NWBO is very eager to get the clinical trials underway. The early stage trial was a phase one trial which was conducted at MD Anderson. It treated 13 different types of very diverse, inoperable solid tumors-pancreatic, breast, lung colorectal, et al. There were very encouraging survival extensions in metastatic patients who had failed all other treatments. DCVax Direct was really encouraging in extremely difficult to treat patient group. Today with all the billions that have been spent by the pharma and biotech industry on cancer development, there is not very much that can be done with patients who have inoperable, metastatic solid tumors.
DCVax Direct is a very promising technology because it is directly injected into the tumor. In many cases, the tumor can't be surgically removed because there are too many metastases or because of where it is located. With image guidance physicians can reach almost any location in the body and inject DCVax directly into the tumor. Ms. Powers said that she’s not aware of any treatment that has had the kind of encouraging results shown in phase one trial at MD Anderson.
Starting Combination Trials
In all of its public presentations about the trial results in the phase 3 trial, NWBO has emphasized the survival extensions with DCVax L when used as a monotherapy in combination with standard of care. This is version 1.0 of the DCVax L technology platform. They are eager to build on that by combining DCVax-L with drugs having different mechanisms of action. Its benign safety profile and broad spectrum lends itself to combination therapies. It is eminently combinable with treatments such as checkpoint inhibitors (Keytruda and Opdivo), targeted therapies, chemotherapies and indeed almost any variety of therapy. They have received considerable interest from various companies. NWBO has some collaboration discussions underway and one of their priorities is to do one or more of those combination trials.
The DCVax-L phase 3 trial was one of the biggest and without question the longest trial ever done in glioblastoma. NWBO believes that it will be major landmark in the field. However, they now want to do trials more focused and using faster path tumor shrinkage endpoints. They want to focus particularly on clinical trials where tumor response (meaning tumor shrinkage) can be the endpoint as opposed to overall survival. Tumor shrinkage be seen in a matter of months while survival takes years. They have so many opportunities that the challenge is choosing the right one.
Partnering
NWBO has had questions from shareholders as to whether they are open to partnering. Ms. Powers cited a couple of examples of potential partnering deals especially now that they have this this tool chest of new technologies and intellectual property. They are looking for deals that have either strategic or financial value. This could be a regional partnering. They have emphasized filing and maintaining their IP in a wide range of countries. They would also consider partnering for a specific application.
Shareholders have also asking about up listing to a national exchange from the OTC. The company realizes that some investors are experiencing difficulties with some brokers with share management and purchases. They will be looking to up list when the time is right.
Conclusion
Ms. Powers in her concluding comments said that she had tried in this presentation to give an overview of a lot of different areas without going into great detail. She feels they have made tremendous progress in the last 18 months and are a different and much stronger company. While there are no guarantees, she believes they are well positioned to get their first product approval and begin commercialization with DCVax-L in the UK. They believe that the infrastructure and the systems that they have been working on for years are in order to build for the day that's now arriving. They have the physical facilities, operating systems and strategies that can facilitate commercialization
She believes that through in-licensing they have built a tool chest that provides tremendous growth opportunities. She is painfully aware that the share price does not currently reflect the progress that has been made. She believes that they can continue making progress in building intrinsic value if they can continue taking action against parties that they believe are artificially manipulating and holding the shares down. They also will work to attract institutional investors. Ms. Powers thinks that the combination of building intrinsic value and fighting back against manipulation will ultimately lead the market to recognize the value.
Nemesis18
Re: kabunushi post# 706255
Monday, July 15, 2024 5:48:34 PM
Post#
706260
of 707496
Why not contact the MHRA's CEO's Office direct then, to find out yourself ?
Or are you afraid to venture outside of this forum to seek answers ?
Go on, take that security blanket off , created by the echo chamber here....
Executive.Office@mhra.gov.uk
The MHRA's CEO's direct email is
June.raine@mhra.gov.uk
Or if you prefer, you can address any questions to:
clintrialhelpline@mhra.gov.uk
And if your feeling particularly brave, why not contact the Chair of the CHM ?..
p.mulholland@ucl.ac.uk
Tuesday, July 16, 2024 1:56:15 AM
Post#
706323
of 707497
And if your feeling particularly brave, why not contact the Chair of the CHM ?..
p.mulholland@ucl.ac.uk
You know that it was Paul Mullholland who presented the DCVax-L P3 data results at New York Academy of Sciences in about an hour long presentation on May 20, 2023, right?
My guess is that no, you didn’t.
sentiment_stocks
Followers 230
Posts 14768
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Alias Born 03/29/2014
sentiment_stocks
Member Level
Re: Smitty5150 post# 707246
Saturday, July 20, 2024 12:42:31 PM
Post#
707253
of 707498
Something seems certainly off in what Nemesis is claiming regarding some sort of hold up. But as I've stated over and over, as sure as you are receiving information from the MHRA that there is no external investigation, I, too, am QUITE sure that what Nemesis states regarding his diagnosis, and his GBM treatment, is what he says it is. What doesn't quite make sense is his insistence that Kings wanted to put him in the DCVax trial. What possibly happened is that perhaps at some time prior to surgery, Kings suggested that if it was found that he did have GBM, he could enter the trial. But certainly after the surgery, when it was obvious there was no tumor (just a few cells) to make a vaccine with, they'd have had to tell him he wasn't eligible for the trial. But even with a small presence of GBM (in the biopsy), they opted to move forward with SOC, which didn't require any tumor present to do so.
It's also possible that the timing of everything that happened during that initial diagnosis and surgery was for him a bit of a blur, as all of that stress leading into this could have made him mix up the times. But his medical records would likely reflect the accurate timeline as to how things unfolded. Perhaps whomever he's been in contact with have already investigated and found there not to be any issue. He has indicated he'll be accepting of that outcome.
dmb2
Re: Doc logic post# 706926
Sunday, July 21, 2024 7:39:11 PM
Post#
707465
of 707475
Doc logic, I think FDA has become more political in recent years, it once was the drug regulatory leader in the world regarding its processes and its scientific decision making. That appears to be changing and it has become more apparent that there is more than a noble agenda of protecting the public at play at FDA, sounds a bit like the USA financial markets. The UK has always been quite analytical in its approach and its processes. We always knew at site inspection time the FDA would require massive documents to review at the site while the UK inspectors would take more time to physically inspect the site, and more thoroughly review the physical processing areas and equipment.
The EU has always been a bit of a maze to work with due to the country differences which still exist, though approvals are now more streamlined due to the single process. There are still country level differences regarding labeling, transportation, distribution as well as quality issue resolution though the ICH process continues to reduce major regulatory differences.
All in all it is fair to say what NWBO has undertaken has been a significant set of accomplishments and their strategy will hopefully turn out to be valuable as well as telling regarding how the FDA has slipped. I would love to know more about their pivot to the UK, but that is probably never to be revealed completely.
I am hoping the PIM designation comes through with some prioritization for DCVax-L approval soon.
GLTA
Citadel and the 6 other market makers have bought 90% of the American stock market order flow. With this, they exact a trading tax on American stock market investors. In the case of Ken Griffin-Citadel ,$10 billion a year is their annual profit via algorithmic spoofing and naked short selling .
$nwbo @alphavestcap @hoffmann6383 @kshaughnessy2 @BrianEgolf2 @SmithOnStocks1 @ATLnsider @TiltMyBrain @glen_bwrhr42
— alphavestcapital.com (@alphavestcap) July 21, 2024
If Judge Woods denies Citadel's motion to dismiss(MTD), will that result in Laura Posner's capabilities moving U.S. regulators to finally address the Citadel tax… https://t.co/hggX3CJ8iB
?Impressive LCM strategy before initial approval! #dcvax $nwbo
— Allen Turner (@AllenTurner206) February 15, 2023
DCVax-L + Poly-ICLC. Est primary completion Jan 2024. Unpublished interim results: ~50% survival at >8 YEARS.
DCVax-L + PD-1. Est primary completion Aug 2024. Unpublished interim results: ~65% survival at >26 mos. pic.twitter.com/T0jAwH65Uo
@d_stock07734
NCI researchers along with Dr. Liau and her colleagues did genetic profiling analysis on tissue samples from the p3 trial. In February the same group of NCI researchers just published a paper on long-term GBM survivors. The interesting part is that in the paper published in February NCI scientists defined long-term survivor as those who lived over three years while in the analysis which involves the p3 trial they chose those who lived over five years as long-term survivors. It is obvious that NCI set a higher bar to evaluate the results on the p3 trial.
Glioblastoma Molecular Characteristics and Immune Microenvironment Associated with Survival Outcomes in Patients Treated with Dendritic Cell Vaccination
https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE249282
Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings
https://academic.oup.com/noa/article/6/1/vdae019/7603818
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174783422
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=172924113
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174700804
Net, net: The MTD ruling comes by 8/15/24, and maybe any day. And it's very likely a denial , which could result in a big cash inflow for $nwbo from defendants' settlements . Coupled with MAA approval in August , the big ramp in cash generating sales finally starts.
⏲️Awaiting Judge Woods’ decision on the MTD⏲️$NWBO
— hoffmann6383 (@hoffmann6383) June 19, 2024
The Case: Northwest Biotherapeutics, Inc v. Canaccord Genuity LLC, 1:22-cv-10185, (S.D.N.Y.)
Plaintiff: Northwest Biotherapeutics, Inc.
Defendants: Canaccord Genuity LLC, Citadel Securities LLC, G1 Execution Services LLC,…
Considering that the Citadel algorithms have “set" the price of nwbo for at least 10 years, it will take the maa approval and/or the dismissal of the MTD to break that grip. Retail and institutional investors have been scared away from $nwbo’s manipulated trading on the OTC market . And it’s that same grip on 1000s of American stocks that earns Ken Griffin -Citadel $ 10 billion per year. And its his $200 million in annual on campaign cotitrbtuions to Congressman and Senators that keeps securities regulators (SEC, Finra, DOJ) from enforcing laws already on the books. But this David-Goliath war(see
@cvpayne
link below) can be turned in David’s favor by the huge cash that can be generated by Judge Woods dismissing the MTD and the MAA approval allowing the start of the commercial sale of DC VAX L. NWBO’s combination trial data has shown MOS extension from 16.5 months with current SOC to 10 years with the Liau combination formulas (see Allen Turner links below).
Impressive LCM strategy before initial approval! #dcvax $nwbo
— Allen Turner (@AllenTurner206) February 15, 2023
DCVax-L + Poly-ICLC. Est primary completion Jan 2024. Unpublished interim results: ~50% survival at >8 YEARS.
DCVax-L + PD-1. Est primary completion Aug 2024. Unpublished interim results: ~65% survival at >26 mos. pic.twitter.com/T0jAwH65Uo
Ken Griffin (12/22/23) and Citadel tell us that he sets the prices of all stocks. Maybe ...Fuhrer of the U.S. stock market as he has total dictatorial control.His $200 million in annual " campaign contributions" ...https://t.co/RE1PVazt9u @alphavestcap $nwbo
— alphavestcapital.com (@alphavestcap) December 23, 2023
flipper44
Re: Red_Right_Hand post# 707004
Saturday, July 20, 2024 9:12:31 AM
My guess is the Court already drafted its decision. Perhaps a vacation here or there delayed all relevant personnel review. I assume a decision will come out this week.
StonkMaster
Re: flipper44 post# 707167
Saturday, July 20, 2024 10:25:06 AM
Post#
707191
of 707302
So are we waiting on a new R&R or a decision on the MTD?
flipper44
Member Level
Re: StonkMaster post# 707191
Saturday, July 20, 2024 12:00:41 PM
Post#
707240
of 707303
Magistrate’s R&R.
dstock07734
Re: None
Saturday, July 20, 2024 11:34:16 AM
Post#
707229
of 707296
NCI researchers along with Dr. Liau and her colleagues did genetic profiling analysis on tissue samples from the p3 trial. In February the same group of NCI researchers just published a paper on long-term GBM survivors. The interesting part is that in the paper published in February NCI scientists defined long-term survivor as those who lived over three years while in the analysis which involves the p3 trial they chose those who lived over five years as long-term survivors. It is obvious that NCI set a higher bar to evaluate the results on the p3 trial.
Glioblastoma Molecular Characteristics and Immune Microenvironment Associated with Survival Outcomes in Patients Treated with Dendritic Cell Vaccination
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE249282
Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings
https://academic.oup.com/noa/article/6/1/vdae019/7603818
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=172924113
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174700804