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kab, the timeline that I proposed for the Flaskworks process approval was rather imprecise, since we don’t know many details. I think that commercial production startup timing may primarily depend on the timing of the marketing approval, estimated approval of the Flaskworks process, and price negotiations with NICE (which are likely based on automated manufacturing), so there’s a few moving parts, each with their own timeline. Those timelines should become clearer the further along they are, but I’ve said that I believe the timelines will come together, and think the plan has been for automated commercial manufacturing from the start.
Generally, there is some time lag between the marketing approval and commercial production startup, as market awareness activities begin, customer care network is set up, protocols are established with hospitals, etc., but I agree that manual production could begin if necessary, once all the pre-commercialization activities are completed, in case the Flaskworks timeline gets extended.
I’ll break it down. 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!
The Illogical Growth in NWBO’s Short Interest:
Date // Short Interest // Milestone
01/12/2024 // 45,906,037
12/29/2023 // 46,139,791
12/15/2023 // 45,776,842 // Marketing Application Submitted
11/30/2023 // 46,647,939
11/15/2023 // 49,260,570
10/31/2023 // 55,750,380
10/13/2023 // 54,229,798
09/29/2023 // 52,330,376
09/15/2023 // 50,976,498 // Linda Liau Appointed to Scientific Advisory Board
08/31/2023 // 48,940,579 // Marketing Application Submission Announced within 30-45 days
08/15/2023 // 47,481,115
07/31/2023 // 44,998,078
07/14/2023 // 44,299,486
06/30/2023 // 43,316,947
06/15/2023 // 41,973,714
05/31/2023 // 40,738,041
05/15/2023 // 39,849,483
04/28/2023 // 37,419,389
04/14/2023 // 39,268,663
03/31/2023 // 39,133,732 // Commercial Manufacturing License Issued for Sawston
03/15/2023 // 39,268,213
02/28/2023 // 40,153,956
02/15/2023 // 39,063,970
01/31/2023 // 38,719,541
01/13/2023 // 41,300,593
12/30/2022 // 41,886,273
12/15/2022 // 41,783,315
11/30/2022 // 38,579,908 // Lawsuit Filed Against Market Makers
11/15/2022 // 27,453,945 // Clinical Trial Data Published in JAMA
10/31/2022 // 27,335,566
10/14/2022 // 27,532,363
09/30/2022 // 28,010,880
2022-09-15 // 29,057,926
2022-08-31 // 30,503,372 // Pediatric Investigation Plan Approved
2022-08-15 // 31,424,311
2022-07-29 // 31,803,013
2022-07-15 // 31,231,677 // Application For Commercial Manufacturing License Submitted
2022-06-30 // 32,876,739
2022-06-15 // 33,595,743
2022-05-31 // 31,736,044
2022-05-13 // 29,024,824 // Positive Top-line Data Released
2022-04-29 // 29,604,478
2022-04-14 // 28,766,916
2022-03-31 // 25,661,442
2022-03-15 // 24,381,784
2022-02-28 // 22,051,004
2022-02-15 // 20,060,226 // DCVax Production Commences at Sawston
2022-01-31 // 19,127,664
2022-01-14 // 17,767,836
2021-12-31 // 16,181,973
2021-12-15 // 15,605,232 // Investigational Manufacturing License Issued For Sawston
2021-11-30 // 13,284,932
2021-11-15 // 12,050,197
2021-10-29 // 12,555,107 // HTA License Issued For Sawston
2021-10-15 // 11,381,523
2021-09-30 // 11,412,754
SHAREHOLDER ADVOCATE COHEN MILSTEIN Winter 2024
Protecting Market Participants from Manipulative Trading
When Congress passed the Securities and Exchange Act of 1934, one of its main goals was to protect the marketplace from the kind of manipulative conduct that precipitated the Great Wall Street Crash of 1929. In the nine decades since, technology has evolved tremendously, and with it the methods devious traders use to manipulate stock prices. But the fundamental threat market manipulation poses to the integrity of securities markets remains unchanged. That’s why Cohen Milstein has developed a series of innovative cases to hold trading firms and individuals accountable when they engage in manipulative securities transactions.
In a class action on behalf of investors in XIV notes, for example, the firm alleged that Credit Suisse manufactured a crash in these securities to obtain illegal profit and we obtained a groundbreaking decision from the Second Circuit holding that these allegations sufficiently pled market manipulation claims. We also represent a class of shareholders in Overstock who allege that the company’s “short squeeze” manipulated the market for its own securities; those claims are currently under review by the Tenth Circuit. And when the Supreme Court considered the scope of key market manipulation provisions of the Exchange Act, we filed an amicus brief advocating for the position that the Court ultimately adopted in holding a broker liable for engaging in manipulative conduct.
Most recently, we filed two market manipulation lawsuits on behalf of dynamic companies in the biotech and information technology industries against some of the nation’s largest broker-dealers for allegedly manipulating the price of these companies’ shares for their own profit. The cases allege that the defendants engaged in “spoofing” to artificially drive down the price of the companies’ shares in order to purchase them at below-market prices.
Spoofing is a form of market manipulation that typically involves placing large “baiting” orders on one side of the market to induce other traders to follow suit, then buying or selling that security on the other side of the market at the artificial prices created by the spoofing, and finally cancelling the baiting orders before they are executed.
The particular mechanisms of spoofing can involve complex features of high-frequency trading algorithms in electronic trading venues. But the basic concept can be analogized to a headfake in sports. A trader fools the marketplace into thinking it is trading in one direction with the goal of moving other traders in that direction, allowing the trader to execute its true trading intention in the other direction, at a greater profit. In our two cases, we allege that the defendants wished to purchase the companies’ shares at artificially low prices and used baiting orders to sell in order to execute buy orders at better prices.
Spoofing in the age of high-speed trading has been prosecuted criminally and civilly by the Department of Justice, Securities and Exchange Commission, and Commodities Future Trading Commission. But private spoofing cases have been very rare. This is in part because government agencies, unlike private plaintiffs, have access to pre-suit investigative discovery tools to obtain and analyze nonpublic trading data.
In our cases, we responded to this challenge by conducting comprehensive and sophisticated analysis of multiple sources of publicly available trading data, matching orders and executions, and applying parameters to identify patterns that courts have held to be indicative of spoofing. These patterns include placing large baiting orders on the opposite side of the market from smaller legitimate orders, cancelling the baiting orders after the smaller orders have executed, leaving the baiting orders on the market for only a short period of time, placing baiting orders behind other legitimate orders to make them less likely to execute, and other conduct contrary to acting as an ordinary market maker.
In both of our spoofing cases, defendants have moved to dismiss the complaint. In the Northwest Biotherapeutics case, briefing has concluded, and oral argument was held on November 14, 2023 before Magistrate Judge Gary Stein in the Southern District of New York. Arguing for the plaintiffs, we explained how our allegations are exactly the type that courts have consistently held sufficient to plead spoofing claims. The defendants argued, as those accused of spoofing always do, that their conduct was normal trading activity, either making markets or trading on behalf of clients. Magistrate Judge Stein recently issued a report and recommendation that agreed with our position on the sufficiency of our allegations as to defendants’ manipulative conduct, scienter, and reliance, and concluded that only our loss causation allegations require more detail in an amended complaint. We await final orders from the district court judges in both cases.
Favorable decisions affirming the sufficiency of these complaints would be a major development towards fairer markets and remedies for companies and investors that have been victimized by manipulative trading schemes.
Raymond M. Sarola is Of Counsel in the firm’s Securities Litigation & Investor Protection practice group. Laura H. Posner is a Partner in the firm’s Securities Litigation & Investor Protection practice group.
https://www.cohenmilstein.com/wp-content/uploads/2024/01/Shareholder-Advocate-Winter-2024.pdf
International regulatory collaboration is definitely increasing. Have you heard of the International Coalition of Medicines Regulatory Authorities? (ICMRA) https://icmra.info/drupal/en/home
Nature article about recent cell therapy deals
some highlights:
dmb, as I’ve said, I’m not as familiar with procedures in the UK, but I believe that the MHRA only uses software tools to validate the application, and recommends that the applicant first perform a validation using the recommended software tools prior to submitting the application, so I’m unsure how an error could occur, unless perhaps some element is missing.
I’m not sure if it’s still true today, but not too long ago, that validation process differed from the US, where the FDA only validates parts of the application with software tools, while other parts are validated by humans, so validation in the US seems to take longer.
And I definitely agree that Northwest Bio has had “sufficient time” to prepare a high quality application, some might even say more than sufficient time. With all Advent’s workstreams developing manufacturing for comparability, stability, potency, product profile, fill/finish, Bosch’s proteomic analysis on the mechanism of action, Shashi Murthy’s work on the potency assay, and I’m quite sure there was more. So yes, it better be complete and high quality!
The rumor is that Vertex/CRISPR’s initial application for exa-cel was rejected by the MHRA, and they were required to refile, so it was appropriate in that case to make a second press release that the application was validated and accepted.
This may have prompted the MHRA to become more proactive with applicants after the pre-submission meeting, to ensure that applications are higher quality.
I totally agree with this senti. Validation is generally just a formality, as I’m sure it is in Northwest Bio’s case. Admittedly, I corrected BrightBoy about the technical difference between initial confirmation of receipt, and the actual validation of the application, but geez, the validation issue has been blown way out of proportion on this board and made to be way bigger than it ever should have been.
Most companies don’t issue a press release for both the submission and validation of the application, but rather just issue a press release that the application was submitted OR accepted, once the application has been validated and officially accepted. Because Northwest Bio’s application was twice delayed beyond Northwest Bio’s own projections, and many were anxiously awaiting the news that it had finally been submitted, I think Northwest Bio chose to release that news as soon as it happened, just to relieve investors before the holidays. I think it’s safe to assume that the application has been validated, assessment has started, and the countdown to approval has begun.
That’s a good point pgsd. I don’t think Dr. Ashkan is out of touch at all, and I’m quite sure that being the point man in the UK for DCVax, he knows better than most what’s possible with the MHRA regarding a potential rapid approval. I do think that, when you are speaking like he was, and responding to questions, his statements shouldn’t be taken quite so literally as some seem to, but rather “a few months” could easily mean six, which is actually still quite fast for a regulatory approval.
I’m not disputing that there are politicians, clinicians, patients and their advocates that desire a very rapid approval for DCVax, some with great influence and knowledge about the MHRA and the process. I personally don’t think that the UK government would view DCVax approval with the same urgency as the Covid treatments, but I certainly don’t know. I’m just saying that after COVID, even innovative treatments that are desperately needed by patients in the UK, have not received the rapid approvals that were promised by these very same politicians and KOLs.
No one is closer to, or more knowledgeable about the capabilities and interworking of the MHRA than it’s own Deputy Director of Innovative Medicines, so when that person says that the goal is to get to 150-day approvals, but they’d be happy with 210 days, that means more to me than some fluff by a politician, or even an estimate by a very knowledgeable clinician.
I knew my approval estimate would not be popular on this board, but I’m not here to get “likes,” just sharing my opinion, and reasoning. I agree with you though that "anything is possible."
Because that was 2023 ex, and this is 2024. For the past few years, the MHRA was too understaffed to review all the new clinical trial applications and marketing applications within their established timelines, so last year the MHRA received extra funding, hired and trained new assessors, and streamlined processes to clear their backlog, and is attempting to meet their established timelines again in 2024.
The MHRA prioritizes some applications over others like generics or other low-priority drugs, so some applications took longer than others, and the applications that you refer to were assessed before new assessors were on the job and clearing backlogs.
I think it’s highly likely that Northwest Bio’s application will receive priority review, since it treats a serious, deadly disease, and is a significant improvement over the current treatment. Plus the MHRA will want to tout its accomplishment for being the first to rapidly approve this innovative advanced therapy, and get it to desperate patients.
I know this is going to be difficult for you and those in your pack to accept, but we ALL know approval is coming. (yes even you) The only thing that’s really up for debate is WHEN, so enjoy this silly argument while you can.
Hi H2R, I think companies are hesitant to comment about their application after it’s been accepted, and in the hands of the regulator. We may see a status update from NICE that they have received the necessary evidence from Northwest Bio for their appraisal, but that’s about all that I expect to hear about the application before the MHRA decision. I think the approval announcement could just come out of the blue one day in late spring or summer.
We know that Northwest Bio is working on many other projects and negotiating partnerships that haven’t been announced yet, so I think we can anticipate hearing about those developments in the coming months.
And, as some like to remind us, Kite and Juno were both acquired in the period after they submitted their marketing applications but before they were approved, as companies often are because Big Pharma likes to announce the marketing approval and receive the media attention, so there’s also that possibility in the interim . . .
I agree meirluc, and I’ve always thought that the plan has been to have automated manufacturing ready in time for commercialization, which includes time for potential extended reimbursement negotiations with NICE. I would not be surprised if everything happens to come together and lines up at the appropriate time.
pgsd, I agree that there are some politicians in the UK, that have been very interested in seeing rapid approvals for this and other innovative treatments. They talk a good game, but what have they done since the rapid Covid treatment approvals years ago? Government agencies are also bureaucratic and lack the ability or motivation to move quickly or implement changes. It finally took the public and industry to pressure these politicians to act this year and provide the proper funding to the MHRA to implement the changes that were necessary to get new medicines in the clinic and eventually to the public.
For years, the MHRA was in line with the EMA, which has a 210-day accelerated approval process, but some politicians in the UK wanted to show that the MHRA can “lead the world” in rapid approvals after Brexit, so they created the 150-day process (without the 60-day clock-off period). Unfortunately, they didn’t give the MHRA the proper resources or institute the necessary process changes to accomplish this, so it has been unable to meet that 150-day target, and approval timelines have actually been stretched beyond 300 days in many instances, due to staffing and other issues.
So at this point, now that the MHRA has finally hired new assessors and streamlined processes, and regulatory backlogs are being cleared, how fast can the MHRA actually review the application? Can they now assess a high priority application in 150 days total as they once touted? (which would be May)
The MHRA’s Deputy Director, Innovative Medicines, Dr. Shirly Hopper said that many would be happy if they could just meet the 210-day timeline again, which is why I think July seems reasonable, but I certainly leave open the possibility that the MHRA can pull a rabbit out of the hat for Northwest Bio, and approve it more rapidly.
Regarding a potential MHRA decision window; some dates to keep in mind:
(note: validation could add a couple of weeks, but the known submission date is used)
80 days from December 20th is Saturday March 9th
150 days from December 20th is Saturday May 18th (80-day first phase assessment + 70-day second phase)
210 days from December 20th is Wednesday July 17th (150 day assessments + 60 day clock off)
Since the marketing application was submitted before December 25th, it corresponds to a CHM meeting on March 21st or 22nd.
If any questions are raised during the first 80-day assessment phase and the CHM meeting, then a letter is sent to the applicant requesting further information. The applicant has 60 days (which can be extended) to respond, (assessment clock is off) and the responses are assessed during the second 70-day assessment phase, and discussed during the next CHM meeting, so these CHM meeting dates are also relevant:
25 and 26 April 2024
30 and 31 May 2024
27 and 28 June 2024
25 and 26 July 2024
29 and 30 August 2024
26 and 27 September 2024
24 and 25 October 2024
21 and 22 November 2024
19 and 20 December 2024
Some potential basic scenarios based on these dates (there are obviously many others):
A
The application receives the highest priority, (like Covid treatments) and the MHRA makes an approval decision before the full 80-day-assessment period is complete, so before March 9th.
B
The application receives high priority, and the MHRA approval decision is made soon after the 80-day assessment, and it’s determined that a CHM meeting is unnecessary, so shortly after March 9th.
C
The application receives high priority, and the MHRA has no questions during the initial 80-day assessment, or at the CHM meeting, and makes an approval decision following the CHM meeting on March 21st or 22nd, so approval decision is made the following week, March 25th to March 29th.
D
The application receives high priority, but the MHRA has questions, and promptly (within a week) sends a RFI after the CHM meeting, which Northwest Bio responds to immediately, and no discussion at a second CHM meeting is necessary, so approval decision is made in April.
E
The application receives high priority, but the MHRA has questions, and promptly (within a week) sends a RFI after the CHM meeting, which Northwest Bio responds to immediately, and the information is quickly considered by assessors and discussed at a second CHM meeting on April 25h or 26th, and approval decision is made in May. (within ~150 days from submittal)
F
The application receives high priority, but the MHRA has questions, and promptly (within a week) sends a RFI after the CHM meeting, which Northwest Bio responds to within 30 days, (end of April) so the information is considered by assessors and discussed at the next CHM meeting on May 30th or 31st, so approval decision is made in June.
G
The application receives high priority, but the MHRA has questions, and promptly (within a week) sends a RFI after the CHM meeting, which Northwest Bio responds to within 60 days, (end of May) and the information is considered by assessors and discussed at a CHM meeting on June27th or 28th, so approval decision is made in July. (within ~210 days from submittal)
H
The application receives high priority, but the MHRA has questions, and promptly (within a week) sends a RFI after the CHM meeting, which Northwest Bio responds to within 60 days, (end of May) and the information is considered by assessors and discussed at a CHM meeting on July 25th or 26th, so approval decision is made in August.
I
The application receives priority, but the MHRA has questions, and promptly (within a week) sends a RFI after the CHM meeting, which requires more than 60 days for Northwest Bio to respond, or assessors require more than 70 days to consider, and is discussed at a CHM meeting on August 29th or 30th, so approval decision is made in September.
J
The application receives priority, but the MHRA has questions, and promptly (within a week) sends a RFI after the CHM meeting, which requires more than 60 days for Northwest Bio to respond, or assessors require more than 70 days to consider, and is discussed at a CHM meeting on September 26th or 27th, so approval decision is made in October.
K
The application doesn’t receive priority, the MHRA has questions, and promptly (within a week) sends a RFI after the CHM meeting, which requires more than 60 days for Northwest Bio to respond, or assessors require more than 70 days to consider, and is discussed at a CHM meeting on October 24th or 25th, so approval decision is made in November.
L
The application doesn’t receive priority, the MHRA has questions, and promptly (within a week) sends a RFI after the CHM meeting, which requires more than 60 days for Northwest Bio to respond, or assessors require more than 70 days to consider, and is discussed at a CHM meeting on November 21st or 22nd, so approval decision is made in December.
So based on these general scenarios, which seem like the most probable?
I would draw a probability curve (normal distribution) with the high area in July and August, so scenarios G & H being the most likely in my opinion, with scenarios F & I, being a little less as likely, and E & J even less likely, etc.
RE: FWIW- My thoughts on MHRA MAA timeline:
Now that the application has finally been submitted, I guess it’s time to start forecasting how long it will take for the decision on approval. First, I think that you laid out some valid points on both sides, and at this point, it’s really anyone’s guess. I personally agree with you that you are “probably too optimistic,” but I think that many on this board would probably agree with your forecast. I lean more to the optimistic side, but tend to be more realistic.
While there is precedent for very rapid regulatory approvals for COVID-19 treatments, that was during a national health emergency, which most would probably argue that Glioblastoma is not. It seems very unlikely to me that DCVax would receive such a rapid approval, considering the application is for novel cell therapy, which has a novel mechanism of action, multiple unique co-developed assays, non-traditional supply chain, which are just some of the many unique and complex issues on the manufacturing side of this massive application that assessors must evaluate, and there are multiple unconventional issues on the clinical side as well.
It’s not a secret that the MHRA has been backlogged since Brexit, which occurred in January 2020, right before Covid shut everything down, resources were diverted, and Covid treatments were prioritized. Like many other businesses post Covid, the MHRA’s resources have remained constrained, and proper staffing has been a problem.
To address this issue, starting last spring, new assessors were hired and trained, and apparently now, staffing levels are finally where they need to be in order to clear backlogs for both new clinical trial applications, as well as marketing applications. Additionally, to speed the assessment process, the MHRA has also focused on improving the quality of the marketing applications themselves, by providing assistance during the pre-submission phase, to ensure that all of the necessary assessment criteria is well understood, and is organized correctly.
The MHRA will prioritize high quality applications for medicines that address an area of unmet need, and the awareness in the UK about the lack of treatment options for Glioblastoma, has been raised by the deaths of high-profile politicians and public figures, so it seems likely that Northwest Bio’s application will receive priority. If it does, given the MHRA’s backlog, but desire to return to established regulatory timelines, and given that Northwest Bio took extra time to ensure the high quality of their application, I think it may be possible for Northwest Bio to receive a rapid decision within the established timeline of 210 days. (150-day assessment with <60-day clock off period) I personally anticipate an approval in the UK in the 3rd quarter, but I remain optimistic that it’s possible to receive an approval even earlier, in the 2nd quarter.
Several articles were published last summer about the delays in the UK, but I will just highlight some parts of one:
Thanks senti, no it’s clearly not based on thumbs up as it was previously, which is unfortunate. I’ve seen questionable posts there with 2 likes, while excellent posts with many likes (like yours) are left off, which made me wonder if moderators were involved. Anyway, thanks again for sharing your insights.
Why isn’t this post a “Most Liked Posts” at the bottom of the page? Do moderators control this?
BrightBoy, clearly you like to use bombastic language, and are a little looser with the truth to get your point across, but to me, misinformation is misinformation, whether it’s negative or positive. Your post appeared to be misinformed, so I clarified the issue. This was not intended to diminish this significant milestone, or any of the accomplishments that Northwest Bio has achieved thus far.
For the past couple of years, Northwest Bio has been almost exclusively focused on completing all of the prerequisites for the marketing application, but now that the application has been submitted, and is in the hands of the MHRA, Northwest Bio can catch their breath, bask in the glory of their accomplishment, while they wait for the application to be validated, (which is more than a few days btw) and then they will have to get right back to work.
Another significance of validation, or “official acceptance” of the application by the MHRA, is that when that occurs, Northwest Bio can finally turn their attention to other matters that have been in the periphery, such as; preparing for a commercial launch, re-engaging with NICE, preparing to file the application in other jurisdictions, finalizing new partnerships, preparing for new clinical trials, obtaining regulatory approval for the Flaskworks' system, and holding an annual shareholder meeting, just to name a few.
Once DCVax is approved, Northwest Bio is going to have a whole other set of tasks heaped on their plate, so yes, I think it actually does matter whether it takes 5, 6 or 7 months for approval, especially for a company that still has a tremendous amount of work to do, and has a history of missed timelines.
That’s incorrect BrightBoy. “Days To Acceptance” has everything to do with when the MHRA’s 150-day-assessment clock will actually start on Northwest Bio’s marketing application. And “what this has to do with approval,” is to attempt to more closely predict the approximate timing of the approval.
The MHRA’s assessment (and clock) does not start until the application has been validated. Regulatory Agencies first perform a technical validation of the marketing application to ensure that all of the essential elements that are required for scientific assessments are included, and that these elements are all organized and located according to the standard electronic Common Technical Document (eCTD) format. While it is true that the marketing application has been submitted by Northwest Bio, and received by the MHRA, it has not been “officially accepted” yet. And by the way, no they don’t “hand it back to the company” or “throw it in the trash” (it’s digital) but if the MHRA needs additional information to complete its validation of the application, it will ask the applicant to supply this by a certain deadline.
Huh. Whatayaknow dennisdave? Would you like to apologize and admit that YOU were wrong? Do you recall this post of mine when many here were claiming approval is likely within 80 days?
Hallelujah! They sure packed a lot of information into that press release. And congrats to all posters who were correct in stating their belief that Northwest Bio would submit the application before the end of the year. Happy Holidays Everyone!
XMaster, the FDA’s “Submission Times” link I posted, shows the average submission size, and the upload duration for BLA’s and NDA’s, so you shouldn’t have to “imagine how long it would take to transfer.” Maybe I should have taken the time to just posted this:
https://www.fda.gov/industry/about-esg/submission-times
Doc, your guess is in the ball park. I’m not as familiar with the MHRA, but the FDA lists their submission times here:
Submission Times
The following transaction times are generated quarterly based on PDUFA submissions. Your company submission times may be above or below these transaction averages, sometimes by a significant amount. There are a number of factors that affect submission upload and processing times. Below are some of these factors:
Internet connection bandwidth: The bandwidth your Internet Service Provider (ISP) provides to your company
Internet connection bandwidth consumption: The amount of available bandwidth is currently in use by the company. Upload speed can be determined by going to: http://beta.speedtest.netExternal Link Disclaimer
Geographic proximity to FDA (Washington DC): The farther your location from FDA, the more network hops are required for your connection to reach FDA. The more hops your connection takes to get to FDA, the longer your submission will take to get to FDA
Data compression ratio (for multi-file submissions) and submission composition: The number of files and folders/directories and the type of data you are sending will affect the speed at which the submission makes it to FDA
End client/user infrastructure: Capacity of end user's machine (processor and memory), network storage performance, and shared vs dedicated machine might also affect the speed of signing the submission and upload
Uploading a submission during infrastructure maintenance (end user's and/or FDA)
Submission traffic during the specific period: Multiple, very large submissions (e.g., over 10 GB) being received concurrently, then the ACK times will vary.
https://www.fda.gov/industry/about-esg/submission-times
About ESG
What is ESG?
The Food and Drug Administration (FDA) Electronic Submissions Gateway (ESG) is an Agency-wide solution for accepting electronic regulatory submissions. The FDA ESG is a highly scalable, easily available, high performance and secure exchange point for FDA and its partners to transact a variety of documents and submissions over industry-standard protocols. The FDA ESG enables the secure submission of premarket and postmarket regulatory information for review. The FDA ESG enables the FDA to process regulatory information automatically, functioning as a single point of entry for receiving and processing all electronic submissions in a highly secure environment. The FDA ESG complies with secure Hypertext Transfer Protocol (HTTP) messaging standards and uses digital certificates for secure communication. The electronic submission process encompasses the receipt, acknowledgment of receipt (to the sender), routing and notification (to a receiving Center or Office) of the delivery of an electronic submission.
FDA ESG provides two methods, WebTrader (WT) and AS2, for making submissions to FDA. FDA ESG has been in production since 2006 and is used by 100s of users to send 1,000s of submissions every day.
* WT: A web portal designed for low volume submitters. WT allows users to login, digitally sign and submissions, and view responses through a simple web interface.
* AS2: A system-to-system connection to exchange submissions with FDA. AS2 requires a Gateway software implementation on submitters end.
Where do Submissions Go?
The FDA ESG is the central receipt point for sending information electronically to the FDA. Within that context, the FDA ESG is a conduit, or "highway", along which submissions travel to reach their final destination. The FDA ESG does not open or review submissions, but automatically routes them to the proper FDA Center or Office. Industry Partners can send a receive documents from the Gateway via a web interface or server to server communications.
https://www.fda.gov/industry/electronic-submissions-gateway/about-esg
ski, I understand what you are saying about unnecessary and overly burdensome regulations, and I agree only to an extent. I think what you’re suggesting is extreme, and potentially would lead to unsafe and ineffective treatments being approved. I believe the amount of information that is necessary to prove that a medication or treatment, (that sick people ingest, and has the potential to kill them) is safe and effective, and can be manufactured at high quality, should be quite rigorous. I for one, am grateful that I live in a country that has high standards and regulations that attempt to protect its consumers and citizens from harm due to corporate greed and malfeasance. I appreciate the cautious approach that the FDA has taken in recent years (after the affordable care act was passed) to cut through some of the unnecessary red tape, and speed the drug development and approval processes.
While I think the JAMA article provided clear evidence that the addition of DCVax to the standard of care, is safe, and did increase survival meaningfully, no I don’t think that alone provides enough information for regulators to approve DCVax. For one thing, the article did not include the manufacturing data and analysis which proves that DCVax can be manufactured to meet commercial specifications, (which could account up to half of the pages in the marketing application) and there’s a significant amount of evidence outside of the clinical trial, (confirming DCVax is safe and efficacious) which I think regulators should also consider.
ski, it’s a team of reviewers. Many of the “1.7 million pages” are supporting documents, such as the clinical case records, manufacturing development work, the statistical, and scientific analysis methods, etc., that the reviewers may want to examine to aid them in their assessments. You’re right though, much like lengthy court electronic documents, the relevant files are searchable. And no, regulators don’t “demand such a document.” They require companies that want to sell a product to the public to provide sufficient evidence to demonstrate that it’s safe and efficacious, the scientific methods used to prove that are adequate, and that it can be manufactured to meet high standards. It would be impossible to do that in 1000 pages.
Here’s the FDA’s review members and their responsibilities:
Review Team Responsibilities
The review teams analyze new drug applications (NDAs) and biologic licensing applications (BLAs). During drug development, the teams also review Investigational New Drug Applications (INDs). Each team member uses their expertise to answer these key questions:
* Is it reasonably safe to study an investigational drug in humans and will proposed studies provide data needed to show safety and efficacy?
* Is the drug safe and effective in its proposed use and do the benefits of the drug outweigh the risks?
* Is the proposed labeling appropriate and if not what should it contain?
* Are the methods used in manufacturing the drug and the controls adequate?
https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/review-team-responsibilities
CDER 21st Century Review Process Desk Reference Guide
Pre-submission Activities
Ensure Readiness for Application through Pre-Submission Activities
During this phase, applicants are strongly encouraged to request a meeting with the appropriate FDA review division prior to the submission of an NDA/BLA, particularly in the case of NMEs and BLAs covered under the PDUFA V “Program,” to discuss the planned content of their application. Meetings include the traditional pre-NDA/BLA meeting and other meetings such as the electronic pre-submission meeting, if necessary. Ideally, good FDA-industry IND interactions and use of pre-NDA/BLA meetings will help to ensure that all submitted applications are complete and fileable.
1.1 Pre-NDA/BLA Meeting (Pre-Submission Meeting)
Meeting Purpose: The purpose of a pre-NDA/BLA meeting is to discuss format and content of the anticipated application, including labeling and REMS (if applicable), presentation of data, dataset structure, acceptability of data for submission, as well as the projected submission date of the application. The meeting should be held sufficiently in advance of the planned submission of the application to allow for meaningful response to FDA feedback and should generally occur not less than two months prior to the planned submission. In cases where the FDA anticipates conducting an expedited review of the application and communicates this to the applicant, the pre-submission meeting may be held closer to the submission date.
Preparing for the Pre-Submission Meeting: In preparation for a pre-NDA/BLA meeting, the OND RPM evaluates the meeting request and meeting package, schedules the meeting with pertinent reviewers and provides them with the pre-meeting background package. The Office of Surveillance and Epidemiology (OSE) RPM is also given the meeting package and informs the OND RPM of the OSE reviewer assigned (as necessary) who should be invited to the meetings. The identified OSE staff members are invited to meetings if issues relating to a REMS, postmarketing safety study, or other safety concern(s) are identified.
The information to be provided by the applicant for the meeting includes:
* A timeline and list of prior FDA meetings and agreements, prior FDA advice, and any development changes. This would include meeting minutes and letters sent earlier, regulatory history, issues raised at the end-of-phase 2 meeting, etc.
* A summary of technical information to be submitted in the NDA/BLA, including the results of the pivotal trials, if they are available, and the proposed dataset structure.
* Highlights of any potential problems, including product quality issues, data integrity concerns, safety signals, etc.
* Proposed draft labeling.
* The proposed format for organizing the submission, including methods for presenting the data and a draft index if available.
* A discussion of the need for a REMS or post-marketing study/trial for any safety issue(s) that has emerged during development or during foreign marketing.
CDER 21st Century Review Process Desk Reference Guide Page 10
* Other information/issues that require discussion.
* List of questions for FDA. ?Reviewers should review the meeting package and also be prepared to discuss internally the potential need for an Advisory Committee meeting, REMS, and PMRs. The reviewers draft responses to the pertinent questions submitted by the applicant. The project manager assembles reviewers’ comments and sends them to the applicant at least 48 hours prior to the meeting. ?Holding the Meeting: At the pre-NDA/BLA meeting, the FDA and the applicant will agree on the content of a complete application for the proposed indication(s), including preliminary discussions on the need for REMS or other risk management actions. Reviewers also describe how data should be presented in the NDA/BLA to facilitate its review. The agreement and discussions are summarized at the conclusion of the meeting and reflected in the FDA meeting minutes. ?For “Program” applications, during the pre-submission meeting the FDA and the applicant may reach agreement on submission of a?limited number of application components not later than 30 calendar days after the submission of the original application. These?components must be of a type that would not be expected to materially impact the ability of the review team to begin its review.?Examples of application components that may be appropriate for delayed submission include updated stability data (e.g., 15-month data?to update 12-month data submitted with the original submission) or the final audited report of a preclinical study (e.g., carcinogenicity) where the final draft report is submitted with the original application. Major components of the application (e.g., the complete study report of a Phase 3 clinical trial or the full study report of required long-term safety data) are to be submitted with the original application and are not subject to agreement for late submission. Any agreement that is reached on delayed submission of application components will be summarized at the conclusion of the meeting and reflected in the FDA meeting minutes. (See also: http://inside.fda.gov:9003/ProgramsInitiatives/Drugs/21stCenturyReview /ucm034190.htm) ?For applications where an expedited review is anticipated, FDA will communicate during the pre-submission meeting that the review team plans to conduct an expedited review and has targeted earlier timelines for certain review activities, including “Program” activities. These expedited timelines will be communicated during the course of the review provided no significant unexpected review issues arise and there are no unexpected changes to the workload priorities or staffing for the review team. FDA and the applicant may discuss at the meeting the applicant’s readiness to launch should an action occur early. ?FDA should request that the applicant submit information on all manufacturing facilities and/or preliminary data on pivotal clinical trials or bioequivalence study(ies) that would be useful in early determination of sites for inspection. ?Meeting discussions may include what data will be submitted to support sought-after labeling or how labeling annotations should be linked to the primary supporting information in the eCTD. Container and carton labels can also be addressed during pre-submission meetings. Review teams should direct applicants to the website for the new requirements for prescribing information. (See New Requirements for Prescribing Information) ?Applicants may request that an application be designated for fast-track review; applicants may also request to submit completed sections of the marketing application for review by FDA (rolling review). (See Fast Track, Accelerated Approval, and Priority Review). ?CDER 21st Century Review Process Desk Reference Guide Page 11
Pre-submission Activities
Minutes from the Pre-NDA/BLA meeting are prepared and archived by the RPM.
1.2 Electronic Pre-Submission Meeting
If technical aspects of the submission have not been adequately addressed with the sponsor (e.g., at the pre-NDA/BLA meeting), an electronic pre- submission meeting may be held at the discretion of the review division 30-60 days prior to the submission of the application. The FDA may recommend this meeting for some applications. The focus of the NDA/BLA electronic pre-submission meeting is on navigation, formatting of electronic files, and layout of the application.
In preparation for an electronic submission meeting, the RPM evaluates the meeting request and works with the Division of Regulatory Review Support (email: esub@fda.hhs.gov) to load any provided (mock) data sets on the FDA computer system that support review of electronic applications. The review division prepares draft responses to any questions submitted by the applicant and sends them to the applicant prior to the meeting. Meeting minutes are prepared and archived by the RPM. . . .
https://www.fda.gov/media/78941/download
Haha senti, you’re “confident that the company is still strongly hoping?” Sounds like you’ve been reading the company’s PR’s so long that you could probably write them!
BTW - I’m strongly confident that the company is strongly hoping that too! :)
pgsd, there was so much misleading information about the DCVax trial because the authors referenced the outdated “First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma” from the Journal of Translational Medicine in 2018. See the footnote:
80.Liau LM, Ashkan K, Tran DD, et al. . First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med. 2018;16(1):142. https://doi.org/10.1186/s12967-018-1507-6
This deception was likely intentional because when you look at the history of this article, it shows:
Article history
Received: 24 August 2023
Accepted: 15 November 2023
Published: 04 December 2023
It seems extremely difficult to believe that the authors did not know about the final results of the trial published in JAMA Oncology in November 2022, which would make the deception particularly egregious in my opinion.
Yet another misleading article bashing DCVax and immunotherapy, in “The Oncologist,” which not surprisingly, notes this about the DCVax trial:
“These data should be interpreted with caution considering the high crossover rate, the statistical design, and the absence of information regarding the stated primary endpoint of the study which was PFS,”
and concludes,
“the role of immunotherapy in GBM remains a challenge,”
Not surprising, because Novocure is listed in the “conflict of interest” by multiple authors multiple times. (I will give them credit for disclosing it though)
Autologous Vaccines
In the context of autologous vaccines as a possible treatment in patients with GBM, there are several early-phase studies in the literature that have evaluated the use of vaccines based on dendritic cells (DCs).78,79 These cells have the task of presenting antigens to naïve T cells to ensure the activation of an adaptive immune response.
DCVax-L is the most studied DC vaccine to date, composed of autologous dendritic cells pulsed with autologous tumor lysate that was evaluated in a phase III study in newly diagnosed GBM patients, in combination with maintenance temozolomide after surgery and combined chemoradiotherapy.80 Patients were randomized 2:1 to receive DCVax-L plus temozolomide vs Placebo plus temozolomide; in case of disease progression/relapse during treatment, crossover was allowed. For the intent-to-treat (ITT) population of 331 patients, the mOS was 23.1 months (evaluated from the date of surgery). Due to the possibility of crossover, approximately 90% of all patients in the ITT population received DCVax-L during the study. Treatment was well tolerated with only 2.1% of patients reporting grade 3-4 adverse events possibly related to vaccine treatment. These data should be interpreted with caution considering the high crossover rate, the statistical design, and the absence of information regarding the stated primary endpoint of the study which was PFS.75
A phase III randomized open-label study (NCT04277221)81 is evaluating the use of Autologous Dendritic Cell/Tumor Antigen (ADCTA) immunotherapy in combination with a standard treatment (bevacizumab) in patients with first recurrence of GBM after the Stupp protocol. The primary endpoint was OS whereas the secondary endpoints were PFS, 6-month PFS, and 1- and 2-year survival rates. Another active but not currently recruiting phase II/III study (NCT03548571)82 is evaluating the use of dendritic cell immunotherapy against cancer stem cells in newly diagnosed IDH-wt, MGMT-promoter methylated GBM patients receiving concomitant radiochemotherapy with temozolomide as first-line treatment. The primary endpoint is PFS, whereas secondary endpoints include OS, assessment of patient-reported quality of life, immunological response by analysis of delayed type hypersensitivity reaction in skin and lymphocyte clonal analysis, and safety
Conclusions
Immunotherapy is clearly a revolution in the treatment of solid tumors. However, the role of immunotherapy in GBM remains a challenge because of the immunosuppressive nature of this tumor and its unique immune environment. Further studies will be needed to better understand possible strategies to overcome the mechanisms of immunosuppression. Data from clinical trials will show the future path, likely combination strategies may play a role.
Conflict of Interest
M.C. declares consulting from Health4U. M.P. declares consulting from Novocure and Health4U. A.I, reports research grants from Carthera, Transgene, Sanofi, Nutritheragene; travel funding from Enterome and Carthera; personal fees for advisory board from Leo Pharma, Novocure, Novartis, and Boehringer Ingelheim outside the submitted work. G.L. declares consulting or advisory role funding from ABBVIE, Bayer, Novartis, Orbus Therapeutics, BrainFarm, Celgene, CureTeq, Health4U, Braun, Janssen, BioRegio Stern, Servier, Novocure, and travel funding from Roche and Bayer.The other authors declare no financial relationships.
https://academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyad321/7458630?searchresult=1
abeta, the MHRA has fixed submission dates for marketing applications, that corresponds with a meeting by the Commission on Human Medicines, who advise ministers on the safety, efficacy, and quality of medicinal products. So once Northwest Bio missed the November 27th submission deadline, the next one is December 25th.
Submission dates for 150-days assessment procedure for national marketing authorisation applications containing new active substances.
The MHRA will operate a 150-day Assessment route for high-quality marketing authorisation applications (MAAs).
For applications containing new active substances, submissions should be received by the following dates in order to align with the meeting dates of the Commission on Human Medicines (CHM).
The Marketing authorisation application dossier should be submitted through the MHRA Submissions portal on or before the deadline as detailed below:
CHM meeting ----------------- Submission deadline
25 and 26 January 2024 —-- 30 October 2023
22 and 23 February 2024 — 27 November 2023
21 and 22 March 2024 ——- 25 December 2023
25 and 26 April 2024 ———- 29 January 2024
30 and 31 May 2024 ———- 04 March 2024
https://www.gov.uk/guidance/marketing-authorisation-application-submission-dates-for-150-days-national-and-european-commission-decision-reliance-procedures
How to Sue Short Sellers: by Citadel’s law firm, Quinn Emanuel:
“That Is Not An Opinion”: How to Sue Short Sellers
JUNE 25, 2021
FIRM MEMORANDA
Short sellers capitalizing on illegal “short and distort” schemes can, and do, wreak havoc on a company’s stock price, reputation, and the reputation of senior officers and directors. All too often, with just a single tweet. When this happens, companies find themselves playing defense—i.e., responding to a sudden drop in market capitalization, as well as (i) regulatory investigations, (ii) securities class actions, and (iii) derivative lawsuits that often follow a “short attack”.
Many companies are sick of playing defense. Increasingly, clients want to stop “short and distort” schemes before they find themselves the victims of unfair, repeat attacks that can act as a drag on share price for years—even if the attacks are baseless. Common law claims such as defamation, unfair competition, and intentional interference with contracts, as well as claims for market manipulation, RICO violations, and securities fraud under federal and state securities laws all sound like appealing avenues for relief. But in practice, few companies decide to bring claims against offending short sellers.
One reason companies shy away from bringing claims against short sellers is because, frankly, the claims often fail. The short sellers’ modus operandi is to publish negative statements about companies they hold short positions in (be it through short reports, social media, podcasts, etc.) while describing their statements as “opinions.” Because opinions are protected by anti-SLAPP (strategic lawsuit against public participation) statutes and the First Amendment, some companies believe that short sellers seem to operate as if they are untouchable. But they are not: companies can and have succeeded on offense.
HOW TO SUE A SHORT
First, carefully vet short sellers’ statements to identify all actionable statements.
The First Amendment and anti-SLAPP statutes do not give short sellers cart blanche to knowingly or recklessly publish false information about a company. To that end, step one in preparing claims against a short seller is to painstakingly review and vet all of their public statements and identify those that cross the line from opinion to fact and which can be disproved. This may require reviewing social media posts, interviews, podcasts, and short reports – all of which are common mediums of short sellers. It may be that the only good news for a company being attacked on all fronts by short sellers is that the more statements the short sellers make, the more likely it is that some of them will be actionable.
The importance of identifying actionable statements is demonstrated through the recently-announced settlement agreement in Farmland Partners, Inc. v. Rota Fortunae. In Farmland Partners, FPI, a publicly traded real estate investment trust, sued a research firm and its owner, Quintin Mathews, as well as the hedge fund that backed the research, after Mathews published an article online that caused FPI’s stock to fall 39 percent in one day. At the motion to dismiss stage, the Court rejected Mathews’ argument that his publication as a whole was a non-actionable opinion, explaining that the use of disclaimers throughout the article such as “I think” and “I believe” “does not lend to automatic protection under the First Amendment.”[1] The Court held that statements such as FPI was “artificially increasing revenues by making loans to related-party tenants” and “neglected to disclose that over 70% of its mortgages have been made to members of the management team” were objectively verifiable and thus not opinions.[2]
On June 20, 2021, Mathews tweeted a settlement press release—a mea culpa wherein he admitted to reporting a litany of “inaccuracies and false allegations based on those inaccuracies.”[3] The press release states that the inaccuracies were made apparent through “the benefit of evidence from years of litigation, including deposition testimony and documents, and also as evidenced by the recovery of FPI’s share price despite the persistence of expensive shareholder litigation against FPI resulting from my article.” Mathews, who held a short position in FPI, agreed to pay FPI “a multiple” of the profits he earned from his short position.[4] FPI’s claims against the hedge fund defendant are still pending.
In Amira Nature Foods, Ltd. v. Prescience Point LLC, Amira, brought claims in the Southern District of New York against short seller Prescience Point stemming from Prescience Point’s short reports stating that Amira’s financial statements were false.[5] As expected, Prescience Point moved to dismiss the complaint, raising the scepter of the First Amendment as a defense. The Court analyzed that defense under New York’s three-factor test, which considers “[one,] whether the specific language in issue has a precise meaning which is readily understood; two, whether the statements are capable of being proven true or false; and, three, whether either the full context of the communication in which the statement appears or the broader social context and surrounding circumstances are such as to signal readers or listeners that what is being read or heard is likely to be opinion not fact.”[6] The Court went on to explain that “[t]his examination does not parse the individual words or statements but instead considers the publication as a whole, asking whether a reasonable listener is likely to have understood the statements as conveying verifiable facts about the plaintiff.” . . . .
https://www.quinnemanuel.com/the-firm/publications/that-is-not-an-opinion-how-to-sue-short-sellers/
HOW QUINN EMANUEL CAN HELP
Quinn Emanuel is one of the few firms that have successfully sued malicious short sellers, and we are not afraid to do so. We frequently advise clients in navigating the muddy waters of short attacks, and we work with the best investigators and economists in the industry in applying the above playbook.
No firm is better suited to guide companies dealing with short attacks than us.
Quinn Emanuel was ranked #1 in the BTI Consulting Fearsome Foursome for 2021, earning the title of “Most Feared” law firm in the world for the second year in a row. Quinn Emanuel was also included in the list of “Top 20 Trial Law Firms” by Benchmark Litigation USA 2021 and received a global ranking of Tier 1 for securities. The Wall Street Journal called us “a Global Force in business litigation”, and The American Lawyer says we are “Better. Faster. Tougher. Scarier.”
***
If you have any questions about the issues addressed in this Client Alert, or if you would like a copy of any of the materials we reference, please do not hesitate to contact us.
yes flipper, I believe that half-truths have been used to string investors along. They know quite well that their current shareholder base is retail.
Thoughts on Northwest Bio’s marketing application:
It’s a massive undertaking to develop a drug and bring it to market, even for a well-resourced, experienced pharmaceutical company that has commercialized many drugs. The difficulty is magnified tenfold, for a small company like NW Bio, that doesn’t have the resources or experience of Big Pharma, and is applying for its very first commercial marketing approval, for a novel cell therapy, that may not be well understood by regulators. It’s not only necessary to run clinical trials to prove the product’s safety and efficacy, but they must also prove their ability to manufacture the product consistently to meet very strict commercial standards in high volumes.
Northwest Bio owns ground-breaking, disruptive technology that one day may help to change the way cancer is treated, and I think It’s managed by some well-intentioned, accomplished people who truly care about helping cancer patients. But it would be a huge understatement to say that Northwest Bio’s management has underestimated the problems and opposition that confronts companies when bringing a disruptive cell therapy to market, as well as the time it takes to counter and overcome them. In my view, their credibility has been damaged by their numerous, inaccurate, often-extended timeline forecasts, half-truths, and repeated delays. I don’t think that necessarily makes them incompetent as some suggest, but the repeated attacks have probably made them wary of the slightest mis-step, and exposure to potential future attacks, which probably affects their actions and communication.
Northwest Bio has navigated and overcome numerous hurdles, and has many accomplishments. As a reminder, they: 1. produced positive clinical trial results, (from a trial with flaws) 2. got those results published in JAMA, 3. gathered evidence, and brought a suit against malicious stock market criminals who repeatedly manipulate their stock, 4. developed crucial manufacturing data, (which is necessary for a successful marketing application) 5. developed an automated, digitized system to manufacture their product, (which is necessary to overcome commercial bottlenecks) 6. gathered and analyzed data from decades-long clinical trials, and converted and digitized that data into a common marketing application, (that will also be used in the US and other jurisdictions) and are now very close to filing an application for their first regulatory approval.
The company had a pre-submission meeting with the MHRA, and is in contact with other regulators, as well as being advised by informed consultants and scientific board members, so if, based on the expert advice they received, they concluded that it was prudent to take an extra month or two, just prior to submitting the application, in order to gather additional data or evidence, that will strengthen the marketing application, (possibly required by the FDA) then how can I (or anyone else) disagree?
I think some of the wording used in the previous, Oct. 13th press release, (and their past history) made it seem unlikely, that NW Bio was going to achieve that very optimistic timeline of submitting the application by mid to late November. Last week’s update, that the publisher now has (most of) the key final section, the publisher’s work has begun, and it may take them several weeks to complete the application, is very positive news. (despite the “distorting” on social media, and coordinated stock “shorting” by hedge funds)
The next MHRA submission deadline is December 25th, which aligns with a CHM meeting on March 21st or 22nd. I’m fairly confident that they will submit the application next month, and beat this deadline.
Yes, the DOJ is exploring RICO charges, and potentially racketeering, in their investigation of illegal short sellers and the “research” firms they pay to manipulate stocks. The DOJ is particularly focused on “spoofing” which most NWBO investors have witnessed firsthand when making trades. I wonder if any information obtained during discovery, in their case against the market makers, will assist in this investigation . . .
The Department of Justice is reportedly exploring if they can charge stock market short-sellers with the same law used to take down the mafia
Feb 24, 2022
Matthew Fox
- The Department of Justice is exploring if they can charge stock market short-sellers with the same law used to prosecute the mafia, according to a Reuters report.
- Several short-selling research firms have been on the DOJ's radar as they investigate illegal trading tactics.
- Subpoenas have been sent to dozens of firms, including Citron Research and Muddy Waters.
An ongoing investigation into the practices of several stock market short-sellers is heating up, and the Department of Justice is exploring if it can use a federal law that was originally enacted to prosecute the mafia, according to a Reuters report.
The Justice Department already sent subpoenas to dozens of short-selling firms last year, including high-profile activists Andrew Left of Citron Research and Carson Block of Muddy Waters.
While no final decision has been made by prosecutors, potential charges under the Racketeer Influenced and Corrupt Organizations Act, or RICO, remain an option "on the table," Reuters reported, citing two sources familiar with the situation.
This wouldn't be the first time RICO charges were leveled against Wall Street participants. In the 1980s, Michael Milken was charged with racketeering, though he reached a plea deal that did not include those charges. And in 2019, JPMorgan executives were charged with racketeering related to the price manipulation of precious metals.
The current investigation into short-sellers revolves around their trading practices, specifically whether manipulative tactics were employed around the same time a negative report was published.
According to prior reports, the DOJ seized hardware, trading records, and private messages from various short-sellers and is focused on the act of "spoofing" and "scalping," two practices that could lead to big gains for traders.
Spoofing is an illegal practice banned in 2010 in which a trader floods the market with fake orders to influence a stock price. Scalping is related to activist short-sellers selling out of their position for profits without disclosing it.
Short-sellers are an unloved group of market participants that get a lot of blowback from the companies they target and the investors of those companies. Some see their tactics as predatory, as they often have the power to move a stock that they might have a position in by releasing a critical report. Critics say these reports use misleading information that doesn't give a complete picture of the situation at hand.
But some short-sellers also have a proven track record of identifying and exposing fraudulent companies that sometimes go bankrupt. Such companies that were the target of short-seller research included Enron, Sino-Forest, and Wirecard AG, among others.
One person who is happy with the Justice Department's investigation is Tesla CEO Elon Musk.
"I am greatly encouraged by the Justice Department investigating short sellers. This is something the SEC should have done, but, curiously, did not," Musk said in an e-mail to CNBC. "They will short a company, conduct a negative publicity campaign to drive the stock price down temporarily and cash out, then do it all over again many times."
Musk's position against short-sellers is not surprising given that Tesla stock was a popular target among short-sellers for many years until it broke out to record highs in late 2019 as the EV maker turned a profit. While 25% of Tesla's shares were sold short in 2019, that figure now stands at just 2%, according to data from Koyfin.
So far, the investigation by the Justice Department has reached nearly 30 investment and research firms that engage in short-selling. No one has been accused of wrongdoing, and the investigation may not lead to charges being brought.
https://markets.businessinsider.com/news/stocks/stock-market-short-sellers-doj-investigation-mafia-law-rico-racketeering-2022-2
flipper, the JTM article says differently:
Patients in both arms continued to receive monthly adjuvant temozolomide (150–200 mg/m2/day×?5 days every 28 days), interspersed with the DC vaccine or placebo treatments administered on Days 0, 10 and 20, then Months 2, 4 and 8, and thereafter at 6-month intervals starting at month 12. Each DCVax-L treatment involved a dose of 2.5 million autologous tumor lysate-pulsed DCs administered intradermally in the upper arm, alternating arms between injection visits. . .
In general, approximately 2 g of tumor tissue was needed to produce the full ten doses for the 36-month treatment and follow-up schedule. The vaccine was aliquoted in individual doses and cryopreserved ?https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1507-6
murcidencelum
murcidencel
autologous dendritic cells (DCs) derived from peripheral blood mononuclear cells (PBMCs) obtained from glioblastoma patients. A sample of the same patients' glioblastoma is also collected, and a tumour lysate prepared. The purified adherent monocytes isolated from PBMCs are initially grown in media containing granulocyte-macrophage colony-stimulating factor (GM- CSF) and interleukin 4 (IL-4) to induce differentiation into dendritic cells, followed by loading of the dendritic cells with the tumour lysate in culture media supplemented with GM-CSF and IL-4. The final cell suspension contains =60% dendritic cells (MHC Class II+, CD86+; CD14-), with =40% of the cells in the suspension being other autologous cells, such as T lymphocytes, B lymphocytes, and natural killer cells. The dendritic cells induce T cell proliferation in a co-stimulation assay cell therapy (antineoplastic)
https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl128.pdf?sfvrsn=889fe54b_3&download=true
DocLee, you’re unlikely to see a number specifically for total DCVax development costs. The accumulated deficit is generally accepted as a reasonable public number for the costs spent by the company to date, since revenues have been extremely minimal, but it does include other expenses to run the company, in addition to the specific drug development costs.
Thanks ATLnsider, so that proves it was for the trial.
So this is the controversial post by Bio99. Unfortunately, this is not the first time that he’s been completely wrong, and he lost credibility with me long ago because of it. There are no “facts” or “many different sources” that “Advent has been running at greater than maximum capacity since May. (hundreds of patients per month potentially)” It’s complete nonsense.
thanks abc, but I'm not so sure that 20221 is a date.