Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Poor Man, sorry I don’t know where Northwest Bio was in the filing process at the time of the regulatory change, nor the level of revision that would be required to update the quality module. I have personally anticipated an announcement of the MAA filing a couple months after the MIA was received, and that hasn’t changed.
Hi dmb2, yes Autolomous’ software can accommodate manual processes, like cell culturing. I currently don’t think the MAA will include the Flaskworks system, but I believe it will be included as a post approval supplement shortly after.
yes ATLnsider, Advent’s relationship with Autolomous is obvious, and I thought it was known amongst the more senior members here. It’s been posted about by Lykiri, me, and a few others over the years. I realize that many here don’t understand the importance of what they do, though. Thanks for highlighting it better for others, and all that you do here.
Poor Man, the supply chan and logistics for an advanced therapy product are considered a part of the manufacturing process, and are included in the quality (CMC) module of the MAA. Any regulatory updates from last year would need to be updated in the MAA.
Thanks senti, you may be right. I know they need a HTA export license for the export of human tissue and cells for starting materials, so I would think it would be necessary for the finished product as well. Either way, I’m sure that Advent knows and will obtain the required export licenses.
flipper, one of the major manufacturing bottlenecks in the UK, is that every single batch must be checked by the Qualified Person (QP) and have a QP declaration before the final product can be released. Batch records for cell therapy products can be several hundred pages long, so if batch records are paper, it requires the Qualified Person to be on site, and it could take several hours or more per batch for evaluation. Data recorded manually, can sometimes be prone to human error and reported incorrectly, documentation may be missing or stored elsewhere, or signatures may be missing, etc. If there are errors or deviations, it could potentially take days to certify a batch. To make matters worse, there’s a shortage of Qualified Persons in the UK; as of a couple years ago, there were estimated to be less than two dozen QP’s performing certification activities of CGT products in the UK. This bottleneck alone highlights the need for the digitization of the manufacturing process, and it is why Autolomous was founded. A digital manufacturing process, and an electronic batch record are clearly essential for scaling at volume for a commercial cell therapy product.
I think what Linda was alluding to at the ASM, is Autolomous’ digital batch verification technology, known as AutoloMATE Assist, which is the third module from Autolomous’ digital platform AutoloMATE. The AutoloMATE Assist project began in April 2021, and was expected to last 24 months. (doing the math?)
The first two AutoloMATE modules were AutoloMATE-eBMR, which digitizes batch manufacturing records, and AutoloMATE-CLOCK which provides scheduling of all critical manufacturing processes and variables, from scheduling leukapheresis, to final administration of the finished product to the patient.
According to Autolomous, it will be the first first digital batch verification solution available to the market that will be fully integrated with both an electronic batch manufacturing record and also have scheduling capability. It allows everything in the manufacturing process (including the logistics) to be monitored, captured, traced, and logged in realtime, and the data is secured using blockchain ledger technology. So when it comes to the batch verification and final release of the product, each responsible department, Quality Control, Quality Assurance, and Qualified Person, can easily and quickly evaluate each manufacturing record, (even remotely) which vastly streamlines product release. It’s a pretty big deal in my opinion.
https://autolomous.com/autolomate/
I think I posted this Mark Lowdell’s investment pitch before which includes a development timeline for Autolomous going back the several years that Linda was discussing:
https://atmpmanufacture.org/wp-content/uploads/2019/11/autolomous-mark-lowdell.pdf
PoorMan, in case you didn’t see it, senti posted the export guidance update which occurred In October last year:
Thanks senti for the links to the MHRA guidance update. That’s what I thought, but didn’t see it.
BTW - for the second question that wasn’t answered; I think the Human Tissue Authority (HTA) license will be updated to show “export” after another inspection in conjunction with a marketing authorization for DCVax-L/Murcidencel in the UK, and Advent obtains a wholesale dealer license (wholesale distribution authorisation) (WDA) for Sawston.
I know the world revolves around Northwest Bio, but it’s not a big deal, it’s just an annual reporting requirement that will now exempt single patient cell and gene therapy products because they have a highly controlled supply chain, the information is actually already reported so it would be redundant, and it’s not necessary to protect the public health. The FDA actually spells this out:
Do you know that Cohen Milstein is representing plaintiffs in a class action against six of those biggest megabanks? For guess what?
You know why Zardiw. Check your DDAmanda Chart; most think NWBO is going to revisit (and pass) that all time high. . . . or perhaps it’s the brilliant posters and fascinating discourse here.
Adam craves attention, just like many politicians. It’s unfortunate that he is effective in triggering so many in order to fulfill this need. He knows that Northwest Bio has a number of outspoken defenders who will respond. The most effective solution is simply to ignore him. And I really wish people would.
Shashi Murthy is a self-admitted “serial entrepreneur in cell & gene therapy.” So it isn’t concerning to me that he lists his current endeavor, Nanite, Inc., which he co-founded, on the top of his Linked In page.
His entire $2M payout from the Flaskworks’ acquisition was paid in stock in NWBO, which only vests when the 4 milestones are accomplished. Does anyone really think he would leave before he makes sure that these milestones are achieved? I don’t.
Advent will be conducting the comparability studies and compiling the data for the regulatory submissions, but Dr. Murthy is likely only consulting and overseeing that the Flaskworks’s team gets the Eden System engineered and capable of producing a commercial product that is essentially equivalent to the established manual process and product.
While I believe the second milestone has been achieved, the only milestone that was confirmed was the first one, to find a new supplier to produce a prototype of the EDEN cartridge within 90 days of the Flaskworks’ acquisition. As a reminder, these are the other 3:
(ii)Twenty-five percent (25%) of the Rights shall vest upon the demonstration to the Company’s reasonable satisfaction that the EDEN system can replicate the Company’s current DCVax-L manufacturing process as verified by yield, phenotype and functional assay data.
(iii)Twenty-five percent (25%) of the Rights shall vest upon the completion to the Company’s reasonable satisfaction of comparability studies that demonstrate equivalence between EDEN and the Company’s current process for DCVax-L, and equivalence of the DCVax-L products manufactured through EDEN and those manufactured through the Company’s current process. For purposes of this Agreement, “Completion” shall mean that all applicable data is available and prepared in a consolidated format sufficient for submission to regulatory agencies in the UK, US, Canada and EU.
(iv)Twenty-five percent (25%) of the Rights shall vest upon approval by the regulator in the US or EU of the comparability of the EDEN process and the Company’s current processes, and the comparability of DCVax-L products manufactured through EDEN and those manufactured through the Company’s current processes, for commercial use.
And do you know why “Researchers at UCLA developed the first personalized vaccine for brain tumors (dendritic cell-based vaccine, or DCVax®)” ?
Because Northwest Biotherapeutics contracted and paid them to do so. It seems that you have a lot to learn so here’s one of the contracts for UCLA to develop DCVax:
Repost: dennisdave, this post is nonsense. This board has very knowledgeable investors who actually know the history of Northwest Bio, and the difference between the words invent and develop, and have read the patents and contracts between Northwest Bio and UCLA? Have you?
Do you understand that the process that Dr. Liau invented and patented is not used or patented by Northwest Bio? Do you know why?
Hint: Here’s one of Dr. Liau’s/UCLA’s relevant patents:
Medical device firms’ payments to doctors far outstripped those from pharma, study shows
April 7, 2021
WASHINGTON — The medical device industry gave doctors consulting fees, lunches, lodging, and other incentive payments worth $904 million between 2014 and 2017, per a new study — more than $80 million more than the pharmaceutical industry lavished on physicians over the same time period.
Experts told STAT that the findings, published Monday in Health Affairs, raise new questions about the industry’s influence on physician behavior — particularly since the medical device industry pulls in far less in revenue than the pharmaceutical industry.
Doctors must report any payments they receive from medical device makers, pharmaceutical companies, and other businesses in a government database called Open Payments that aims to help patients, researchers, and journalists understand the financial relationships that might be influencing a physician’s opinion. But until now, virtually all of the attention and scrutiny of the payments, as well as research into the links between the payments and physician behavior, has focused on pharma.
While a tight-knit relationship between medical device firms and physicians is often necessary for training and product development, the large scale of payments may inhibit the public’s trust between the patient and their provider, the researchers and other experts said.
If the relationship between the patient and physician is “contaminated by perverse financial incentives, then it does erode the public trust, which is a sacred value in our heritage, our great medical heritage,” said Marty Makary, professor of surgery and health policy at the Johns Hopkins School of Medicine, who was not involved in the research.
Medical device firm representatives often work side-by-side with physicians in the operating room, educating them on how to use their product and receiving feedback for developmental purposes. Helping a doctor learn how to use a pacemaker or insulin pump is very different from explaining the dosages of a new pill.
This intimate relationship has sparked the development of breakthrough medical products. But medical device representatives often use the increased face-time with physicians as an opportunity to pitch their products, according to the study and industry experts.
Both Alon Bergman, co-author of the study and postdoctoral researcher at the Leonard Davis Institute of Health Economics and the Wharton School, and Aaron Mitchell, an oncologist and health services researcher at Memorial Sloan Kettering Cancer Research Center, worried that the influence of a salesperson in the operating room creates blurred lines when doctors are deciding which product is best.
“I find that problematic,” said Mitchell, who was not involved in the research. “It becomes a lot harder to [decide which product is best] when that salesperson is also taking you out to $500 dinners and pays you tens of thousands of dollars in consulting fees over the last few years.”
https://coi.ufl.edu/2021/04/07/medical-device-firms-payments-to-doctors-far-outstripped-those-from-pharma-study-shows/
ski, when Corning sold the MicroDEN system, the retail price for the single-use consumable kits, which included the culture cartridge, PET tray, and two media storage bottles, was around $1000. So I would assume that the cost of the kits purchased through a supply agreement directly from Saint Gobain, would be in the low hundreds.
As far as the disposition of the consumables, I think the wiring and sensors attached to the Flaskworks system may be reused, but the single-use kits are exactly that; single use. They are considered biomedical waste and must be disposed of according to federal regulations, which is generally chemical disinfection, autoclaving, and incineration. In this case, I think the kits would be collected and eventually incinerated.
skitahoe, I know for certain that Saint Gobain does not “load anything into the culture cartridge” when it’s manufactured. Saint Gobain manufactures lab supplies, not cell-therapy treatments.
In this case, the Eden cartridge is manufactured in a similar way as other tissue-culture flasks. The plastic polystyrene surface on the bottom of the Eden cartridge is subjected to a plasma gas treatment in order to make it more hydrophilic. The resulting surface carries a net negative charge which increases cell attachment. Additionally, the cartridges are likely sterilized using gamma irradiation to prevent contamination.
The patient’s monocytes are adherent cells, so in the lab, when the monocytes are loaded into the Eden cartridge, they adhere to the bottom surface. When the culture medium is perfused into the cartridge, the cells attached to the bottom are continually surrounded with culture medium.
meirluc, check out Store My Tumor:
https://storemytumor.com
FREQUENTLY ASKED QUESTIONS
https://storemytumor.com/faq/
FINANCIAL QUESTIONS
1. Are there other organizations that offer this type of service?
Currently, Store My Tumor is the only organization that offers viable tumor storage and logistics services privately. We are a trusted partner for cutting-edge cancer centers worldwide. Live tumor storage requires top-quality facilities, highly-skilled technicians, and precise timing and logistics (in other words, zero mistakes). We take this responsibility very seriously
2. What is the cost to collect, process and store my tumor?
Costs associated with tissue cryopreservation depend on the formats required. Our services include a specially-prepared collection kit, shipping, custom processing and a research consultation. Please contact us to discuss details. Once we understand your needs and priorities, we’ll send a registration packet which outlines the recommended storage options and costs of our services.
3. Is this expense covered by insurance?
While we have had a couple of patients successfully receive reimbursement from their insurance companies, we generally set the expectation that this is an out-of-pocket expense. We will provide an itemized invoice that you can use to submit a claim.
4. I can’t afford the service. Can StoreMyTumor help?
Depending on your situation, financial assistance may be available. We understand that a cancer diagnosis comes with numerous unplanned financial demands. Please ask for a Financial Assistance application to submit with your registration. We will try hard to not let cost stand in the way of your commitment to your future.
Yes, “the FDA has Mutual Recognition Agreements in place with the EU and the United Kingdom, respectively,” but did you read this part?
That’s a reasonable suggestion flipper, but it’s been my observation that, while Dave serves a valuable purpose, he’s been unable to answer seemingly immaterial questions in a direct manner, so I haven’t talked with him in a couple years. In this case, it could reveal a commercialization strategy.
I thought that Northwest Bio was planning a slow (go-it alone) commercialization rollout only in the UK this year to work out the commercialization kinks, and then later next year expand to the US. Using fresh monocytes, and regional manufacturing would be fine for this type of commercial startup. However, if Linda is taking about global distribution, and redundant manufacturing, possibly implying a much larger commercial rollout, (potentially with a strategic partner say for Project Orbis) then cryopreserving leukapheresis material would absolutely be necessary. Let’s hope that Advent has been working on this since before I first raised the issue in 2021.
By the way, the first approved CAR-T manufacturers (Kite & Novartis) both cryopreserved their leukapheresis material early in clinical trial development, in recognition of the eventual logistical necessity for global distribution.
Dr. Toms confirmed the leukapheresis is done in the UK, so fresh monocytes.
Excellent work froggmister. Thanks for the transcript.
skitahoe, I would speculate the cost to produce DCVax manually is a little less (maybe 50k) than the compassionate-use price that Advent charges (£250k). The cost savings achieved by moving from isolated high-grade clean rooms to a lower-grade cleanroom environment, cutting fifteen manpower hours of culturing labor down to three, automation and digitization of batch records, economies of scale, etc., by using the Flaskworks system, would be very significant, perhaps around 40%.
NICE initially refused to cover both of the expensive CAR-T treatments, Kymriah, and Yescarta, which seems somewhat common during early stages of negotiation, but did eventually recommended covering both treatments after discounts were negotiated (Novartis cut their list price down to £282k) or limiting coverage through managed access. So yes, I would agree that some acceptable pricing arrangement would be found for DCVax if manually produced, but NICE may restrict coverage initially if the price is too high.
Ordinarily, NICE considers new treatments cost-effective if their cost per quality-adjusted life year (QALY) gained is between £20k-30k, meaning the cost to the NHS for a year of good health does not exceed that threshold.
meirluc, that is certainly a reasonable way to read it. I don’t think they really knew how long it will take to get the Flaskworks process approved, and I think they are adding cleanrooms at Sawston because they will need the extra cleanroom space for commercial production demands, whether it begins manual or automated. I think it would depend on where Flaskworks is in the comparability/approval process when DCVax is approved. It has always been questionable to me whether NICE would approve the high cost of DCVax with manual production, so I’ve thought that they’d wait for the Flaskworks system if it was reasonably close to approval.
I don’t know what grade of clean rooms are currently being built, but I’m speculating there will be a mix of both high (grade B) and low level (grade C & D), similar to phase 1a. Even with the closed, automated production process with the Flaskworks’ system, a low level of cleanroom is needed, generally a C or D grade. Additionally, there are still some processes, like the lysate preparation, assay testing, etc., that will require higher level, B-grade clean rooms.
Thoughts on the Annual Shareholder Meeting:
While management was careful not to give away any specific information that could potentially be used against them, I think they still gave a candid, general idea of what they’ve been working on, where they are, and what are some of the next steps. There has been some important progress made this past year, but much remains, and I think 2023 will be a very pivotal year for the company, with many years of work finally culminating in the first regulatory approval of DCVax.
Preliminary
It’s clear that the company has the support of the majority of investors, with every item on the proxy passing. (this, despite all the negative postings by the supposed shareholders on this board voting no) By the way, while I voted yes on everything else, I do not support the excessive share grab (~20% of the company) by Linda Powers and others, but it never matters. I would like to reward them for their hard work with a reasonable amount of shares, (5-10% of the company) but we were not given that choice. I’ll be curious to see the actual vote totals.
Sawston
Now we know that Sawston was inspected in the beginning October and Advent is far along in their corrective actions, so I anticipate that the commercial manufacturing license will be granted this month, or possibly next. We also now know that construction on phase 1b (expanding Advent’s production development space, and adding more cleanrooms) has been on-going for months.
Marketing applications
Before the meeting, I posed the question: “has Northwest Bio requested or received any accelerated approval pathways from any regulator?” The Common Technical Documents of the marketing approval application (except parts of the first module) are the same for most jurisdictions, so Northwest Bio could request accelerated approval from each country’s regulator, and file separate applications in each country, or potentially they could have simultaneous review of the application by the different countries if they are participating in the FDA’s Project Orbis. Linda’s language that “we have teams of specialized consultants for the different portions of the application package” is consistent with a rolling review in the UK (which I think is highly likely), but it’s still unclear what route(s) Northwest Bio plans to take, only that they “plan to be strategic about filing in multiple places.”
The timing of the final submission of the marketing application is also uncertain, but it seems they are reasonably close (2-3 months?) per this language; “And so on this front, as on the overall picture that we still have more to do. There's still a ways to go on all the document work, but we have come a long way already.” and “It can take an entire year to put an application together . . . we’ve been working on portions of it, as I said, all year long.”
Flaskworks
I posed this question online, but also asked an acquaintance who was attending the meeting, if he could ask, “Is Flaskworks’ Eden system a part of the commercial license application?” He matter of factly said, “there’s no need to ask, it’s not.” I was a bit surprised, and asked how he “knew” this, and he replied that he has provided capital to the company before, and remains in contact. He didn’t have any specific knowledge exactly where Flaskworks is in the development process, or how long it would take for the comparability process.
The testing of multiple versions of the system with high-flow perfusion, slow-rate perfusion, and static culture, that Linda described, was simply part of the performance qualification process, so not really news to me. Knowing now that the inspection of Sawston didn’t occur in September when Advent was hiring for multiple computer validation, and software/firmware script writing positions, along with Flaskworks hiring of product development engineers whose responsibilities include “Identifying design improvements and integrating technology for monitoring cell culture to ensure reliability” could indicate that Flaskworks was still working on the biosensors, and in-process controls with Advent, and the software data integration with Autolomous’ Manufacturing Execution System that is deployed at Sawston, and required for the commercial process. The language used by Flaskworks, “to ensure reliability” sounds like additional commercial validation work was necessary.
Like everything else Northwest Bio is working on, the commercial development of the Flaskworks’ system has taken longer than I expected. As I’ve said previously, there is a relatively short regulatory process to get it approved for use in the commercial manufacturing process once it can repeatedly and reliably produce a highly similar product, so I’m still optimistic that it will be approved by the same time that DCVax is approved.
So many of us are left to speculate about what’s going on with the company, while others are apparently “in the know.” This can be frustrating, but I understand that it’s common that investment bank analysts have access to management, and have knowledge about the companies they cover, that retail investors don’t.
reality check
Northwest Bio’s technology, their associated scientific advisors, and medical doctors, have always been on par or better than anything from Big Pharma, but this shareholder meeting was another reminder that Northwest Bio is still a tiny company that is under resourced and almost, but not quite, ready for prime time. They are continually behind schedule of where I, and many others, think they should be. There are many examples of this but a couple highlighted during the meeting; the contractor that is now working on all the patient data files that Linda described, could have been tasked and finished with this work over a year ago, rather than still working on them over the past few months. Northwest Bio has a single supplier for a critical manufacturing component, and when that supplier is lost, they must vet another supplier which takes many months, while Big Pharma companies have many suppliers who have been properly vetted, and they can simply switch without causing delays.
Northwest Bio would benefit greatly from the resources that a strategic partner would provide, but are unwilling to make a deal that doesn’t properly value their technology, and they seem willing to wait until they’re better positioned to negotiate more favorable terms. This may not happen until they have received marketing approval, an uplisting on a major stock exchange, and have received the institutional investment support, as well as the proper media exposure, that their treatment warrants. The good news is that it appears that this is finally the year that those important milestones will be reached, and there is a plan to achieve these milestones, possibly without the help from Big Pharma. I know that Linda and Les have access to a significant amount of private capital, but may be waiting to access it until a marketing application has been submitted (and possibly approved) and Northwest Bio is finally ready for commercialization, which may be in conjunction with an uplist. This could gain the institutional support and analyst coverage that would bring the needed major media attention, which could propel Northwest Bio to the next level (and out of the control of the current market manipulators).
Shareholders are clearly not being told everything that the company is planning, and working on, so I do anticipate a few pleasant surprises this year.
Moderators, please sticky this. There are 6 moderators, and only 5 stickies; one of which is over 2 years old and irrelevant. (I mean the sticky is over 2 years old and irrelevant, not the moderator) :)
Fireman, the origins of Keytruda are fascinating, and confirm that even blockbuster drugs are often acquired. It wasn’t a coincidence that after hiring Dr. Duffy from Merck, Keytruda replaced Bristol Myers’ Opdivo in the UCLA study. And yes, you can bet that Merck (and Bristol Myers) are acutely aware of the unprecedented results that were published in JAMA, and recently shared with the public by Dr. Liau . . .
I agree with your relative that at some point, those entities holding short positions will have to cover, but I would disagree that the timing will be in the coming days. This tweet ( on Christmas) by the notorious Aussie short seller, John Hempton, would seem to indicate that at least some may be willing to drag this out:
It is obvious as to why.
— John_Hempton (@John_Hempton) December 26, 2022
If you are gullible enough to fall for the $NWBO scam you are gullible enough to fall for others.
Scammers spam there because the place is full of wood ducks.
Now where have we heard that name before? Martin van den Bent sounds familiar. . . Oh, that’s right, he and Wick also wrote another hit job on DCVax when the interim results were published in the JTM:
First results on the DCVax phase III trial: raising more questions than providing answers.
Wick W1, van den Bent MJ2
Author information
Neuro-oncology, 01 Sep 2018
In today’s pathetic and false critique in Neuro-Oncology he notes this:
Smokey, I don’t think it has to do with Flaskworks per se, but is consistent with a commercial process. GMP for an investigational product only requires final-product testing, and initially, it appears that Advent outsourced their final-product sterility testing, which normally takes a couple of weeks. This would make economical sense in the limited quantities they were sending out, but would make less sense for larger quantities of a commercial operation. In-house sterility testing would also be important for in-process testing that is required for the validated commercial process.
I would agree with that dmb, but I don't have any direct experience or knowledge of the MHRA process either.
Changes were made to the methods and processes for health technology evaluations in the UK. Evaluations that were started prior to February 1, 2022 will be evaluated using the oder methods. However, new evaluations will benefit from the use of the updated and more flexible process. Perhaps Northwest Bio would prefer to begin a new evaluation so that DCVax-L is evaluated using the updated methods and processes?
Thanks wavelenthy! You beat Lykiri to it :)
thanks for the additional info Roman. The job openings I was discussing were in September, and I believe they’ve been filled. (I thought I had a list but can’t find it) Also, this guidance document may be relevant:
EudraLex The Rules Governing Medicinal Products in the European Union
Volume 4
Good Manufacturing Practice
Medicinal Products for Human and Veterinary Use
Annex 11: Computerised Systems
https://health.ec.europa.eu/system/files/2016-11/annex11_01-2011_en_0.pdf
meirluc, NFL football fans may know that when a new rule is implemented for a new season, very often during the preseason, that rule is the focus of the referees attention and they will call the penalty excessively in order to get the attention of the teams about the new rule.
Similarly, some regulators/inspectors will do the same, and focus their attention on certain elements during an inspection, (like computerized systems) and a new system like Flaskworks, will receive extra scrutiny. This potential additional validation was pure speculation on my part. I’m very familiar with a small company like Advent, with limited resources and experience, and I think it’s possible that Advent anticipated that the inspectors would find some issues that were insufficient, and allowed the inspectors to pinpoint exactly what they were looking for, and then Advent addressed the specific issues. If there was going to be an excessive delay, I think Northwest Bio would inform shareholders. So far this hasn’t occurred, so I’m optimistic for an update by the end of the year as well.