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Lykiri, of course I agree with you “that the changes to the manufacturing of the ATMP must be supported by the data generated in a comparability exercise.“ However when you say “IMO, this is valid for both investigational ATMPs and authorised ATMPs,” are you saying that you think that only a comparability exercise for the Flaskworks system is all that’s needed for commercialization? If so, you’re probably in good company, but I think we may be reading into some information differently.
The way that I read the quote that you highlighted from the Arnold and Porter Blog is that it’s saying that the data from a comparability exercise for an investigational product should show evidence that the post-change investigational product is equivalent to the pre-change investigational product, and the data from the comparability study for a commercial product should show evidence that the post-change commercial product is equivalent to the pre-change commercial product. There are different GMP for investigational products than for commercial products, so the comparability exercise for each type of product should comply with the GMP for that type of product.
I don’t think a comparability study alone will provide sufficient evidence for regulators to conclude that an investigational product is equivalent to a commercial product, and it will require additional process validation and development documentation, which may or may not be occurring simultaneously. It makes sense to me to do this all at the same time for expediency, but there’s always unknown factors that may make expediency less of a priority.
dmb, I agree that surely Flaskworks possesses all of the relevant development documentation for their systems. However, I think the professor was just giving a general answer to a general question, and it does not appear to me to be specifically discussing the Flaskworks’ system, which was previously sold commercially by Corning.
Most of the new closed automated manufacturing systems use single-use consumables, and I think the testing that he discussed was to ensure that no chemical substances leached from the plastic consumables, which is a well-known potential issue. Corning obviously would have done this testing prior to selling their consumables for the Flaskworks system, but it’s unknown if the new supplier (Saint Gobain) can provide the same assurances, or test results, so it’s a good point.
https://www.eppendorf.com/product-media/doc/en/146279/Consumables_White-Paper_026_Consumables_Leachables-Minimizing-Influence-Plastic-Consumables-Laboratory-Workflows.pdf
Thanks for sharing Lykiri. He was a good person to ask, and I would think he knows about the system and process you were describing but because of the vague way the questions were asked, his answers were more general and less specifically helpful, so this is my two cents:
To the first question: Advent is changing a part of the manufacturing process with the Flaskworks system, so they will need to prepare a Comparability Protocol (CP) which s a comprehensive plan that describes the specific tests and validation studies and acceptable limits to be achieved to demonstrate the lack of adverse effects that the Flaskworks system has on the identity, strength, quality, purity, or potency of the final product. So the Regulatory Authorities will approve the manufacturing process changes using the Flaskworks system rather than actually certifying the system itself. If the current process is for an investigational or clinical product, then then the system will only need to comply with the Good Manufacturing Practices for an investigational product.
To the second question: For the CP, the Regulatory Agencies require data from a minimum of 3 runs (in a row) post process change for comparison, and this is the most common number submitted. However, I would guess that Advent has likely run between 20 to 30 tests prior to the study for Performance Qualification, and to “dial in” the system for Northwest Bio’s product.
To the third question: Often a CP is submitted as part of the MAA or BLA in the CMC section, or later as a post-approval supplement. Irregardless of where Northwest Bio is in the marketing application process, the CP could be submitted on its own, and I believe the Regulatory Agencies have a 60-day window to approve it, but this could be delayed due to Covid backlogs or other more critical issues. The professor raises an issue about the testing of the new EDEN consumables from Saint. Gobain. A comparability study may be required for the new plastic consumables as part of the second Flaskworks’ milestone. This may be why Northwest Bio has not reported the second milestone in the 10-K, as this consumables comparability study may be part of the larger CP, and it would likely be submitted all together, so the second, third, and fourth Flaskworks’ milestones may be recognized together when the CP is approved.
great post senti, and interesting aside. Yes Brad Loncar has a “Biotech Launch Database” on his blog that tracks sales of many drugs including Kite’s. These cell therapies are on pace for about $1B in sales this year - Yescarta & Tecartus are here: https://www.loncarblog.com/yescarta-sales
Also of note: Gilead’s CEO, Dan O’Day made some interesting comments about the state of cell therapy itself reaching a “fundamental turning point” last year. Not so much for reaching that level of sales, but for Yescarta potentially moving from a third-line setting to a second-line therapy. Big deal right?
That should tell everyone just how significant it would be for DCVax to be added as a front-line, Standard of Care for both ndGBM and rGBM. Kite is competing with Novartis and other new upcoming treatments for a second-line and third-line setting for a relatively small market. (and still able to make $1B in sales) Meanwhile, Northwest Bio is basically set to own the brain-tumor market!
Shifting from megamergers to strategic collaboration: M&A predictions for biopharma
30 March 2022 | By Hannah Balfour (European Pharmaceutical Review)
Some interesting highlights:
In 2021 we saw deals move away from the massive megamergers of 2019 to smaller collaboration and partnership agreements.
This trend of increasing activity but decreasing value, which Baral expects will continue through 2022, is due to it being a seller’s market. He pointed to several factors promoting a shift in negotiation power away from Big Pharma companies towards smaller enterprises: “One is the patent cliff. All the big pharmaceutical companies are exposed to this cliff looming from 2025 onwards.” According to Baral, the internal pipelines of these large companies are not sufficient to overcome the growth gap potentially created by the fall in revenues after branded medications go off-patent, making them heavily reliant on external innovation.
However, it is often not as simple as directly acquiring companies and assets, because the valuations for these smaller companies are extremely high. Given the ample capital that is accessible for these smaller enterprises to enable their continued development, they are “not in a desperate mood to sell” explained Baral. He added: “The existence of this valuation premium puts pressure on buyers to demonstrate quick returns on any acquisitions they make, acting as a deterrent to transactions – and increasingly making partnerships and collaboration the preferred method.”
“The 60 percent fall from the 2019 peak is because people are skeptical, cautious about doing big deals and paying up front,” explained Baral, adding that, combined with the reluctance of smaller companies to sell, organisations are entering into collaborations or partnerships. These deals enable access to some assets, allow the larger companies to go in small, gain an understanding of the technology, people or market and then, if it seems promising, potentially acquire the company or asset.
An example of this is Pfizer’s investment in – and subsequent acquisition of – Trillium in 2021. Initially in 2020 Pfizer invested $25 million in Trillium, buying approximately 2.3 million of its common shares;2 then in 2021, Pfizer went on to acquire the company for a further implied equity value of $2.26 billion.
As demonstrated above, the main impetus for M&A activity is the diversification and expansion of portfolios, according to Baral. He noted that these deals are occurring across a wide range of indications from oncology to immunology, neurology and more, but the key emerging areas are cell and gene therapy, mRNA, antibodies and protein degradation therapies. The first two are particularly key, according to Baral, who noted there has already been an uptick in interest and valuations for cell and gene therapies and mRNA. “These are platform based and people are really focused on how you can use that platform for not just one therapeutic area, but across many therapeutic areas and diseases,” he added.
M&A looking forward
Baral concluded that he anticipates 2022 will see very similar deals to 2021, with a lot of bolt-on acquisitions and a focus on collaborations and partnerships. “What is changing is there is ample capital in the market, so the power is shifting a little bit from Big Pharma to the mid-sized biopharma companies. They have a little more bargaining power now, with the innovation deficit and access to capital. Pharma companies are in desperate need to fill their pipelines for the looming patent cliff, so we expect a lot of deal making in 2022 and 2023. Now, they are not all going to be megamergers, but the valuations are high,” commented Baral.
https://www.europeanpharmaceuticalreview.com/article/169807/shifting-from-megamergers-to-strategic-collaboration-ma-predictions-for-biopharma/
antihama, I should have said that Advent is not licensed for commercial production at Sawston. Advent received MHRA authorization for the manufacture of Investigational Medicinal Products (IMP). You’re correct that this requires Good Manufacturing Practice, but GMP for an investigational product are different than for a commercial product. Each clinical or investigational batch can vary widely depending on the skill of the technician or other factors, but commercial manufacturing requires far more consistency and reliability. Each stage in the commercial manufacturing process must be characterized and fully validated, which builds quality into the final product. The FDA defines process validation as, “…the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product”. Investigational products do not require process validation, and only require end-product testing. There will also be different requirements for cleaning, packaging, distribution, and documentation, etc., for a commercial product.
After Northwest Bio applies for an MAA, the MHRA will still need to conduct another inspection of Sawston to insure that Advent’s Quality Management Systems are designed to meet the challenges, and comply with the principles of Good Manufacturing Practice for a commercial product.
It seemed to me that everyone was equating Flaskworks certification with commercial production readiness, which isn’t necessarily true, and why I wrote a post a while ago about the necessity of commercial process development. If the Flaskworks system is simply certified for use in investigational medicinal products, it would be an important validation for the system, but it would later require process validation for commercial production, which doesn’t make sense to me, unless commercialization is further away than I thought.
Those job openings are fairly common in the industry, and I don’t think much can be read into them. I think Advent is developing a commercial process for DCVax-L production in their development labs if that is what you mean. Sawston is not licensed for commercial production, so it’s unlikely that commercial activities are occurring there. Advent will apply to the MHRA for a commercial license when they are ready, and I would think that Northwest Bio will inform shareholders when that occurs, just like they did for the initial license.
yes, warrants and options were suspended until May 15th, but it’s unclear exactly how many. From the 10K:
dmb, I agree that Northwest Bio has been working on multiple parallel tracks simultaneously, and I’m reminded of a shareholder meeting when the question was asked if Northwest Bio was dong some of the multi-month processes in parallel where possible, and Lind Powers responded rather sarcastically, “Yes, the thought has occurred to us.” haha
Mountains have been moved to get this treatment to where it is now, and I believe there are just a couple remaining obstacles beyond their control that are holding things up. Many things are lining up, so once the remaining obstacles are cleared, I believe things will move much more rapidly.
Kaizenman, Shashi Murthy developed the BATON system for Neon Therapeutics back in 2016, and he began applying for the patents years ago. I don’t think this was the manufacturing system that Northwest Bio wanted, since they use the dendritic cells as a therapy. So I think this closed, automated T-cell manufacturing system was a bonus that came with the Flaskworks acquisition, but there are many aspects of it’s culturing process that overlap with the EDEN culturing process of the MicroDEN system that those patents could protect. I’m not sure what their future plans are for the system, but having it patent protected will certainly add value.
There's a couple other posts about the BATON system that provide some background:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167176812
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=163095772
jimmy, I also appreciate the many intelligent people here with a wide range of knowledge and experience, who take the time to share their different perspectives and insights on this board. BTW- I consider you among the long list of of value-added posters.
jondoeuk, I thought all this neoantigen talk would get your attention. Thanks for your insights, and keeping us abreast of the competition. ;)
yes, exactly, it's a natural approach to loading the T-cells with your choice of antigens. The T-cells are obtained from the patient's leukapheresis material, then loaded with the antigens specific to the patient's tumor by the patient's dendritic cells, which are also obtained from the patient's leukapheresis.
I think you have it right senti, neoantigens are not found on normal tissue and are tumor-specific. They can be highly immunogenic as they are recognized by the immune system as non-self, so they make good cancer targets. You have probably even heard jondoeuk gushing about development on various neoantigen-based treatments. :) But it sounds like you may be struggling with the question: How could targeting neoantigens be better than DCVax which targets all the antigens?
Short answer is, I don’t think it is a better approach than DCVax. But T-cell treatments have been all the rage since the CAR-T treatments Kymriah and Yescarta were approved in 2017, and there is a general belief that T-cell therapy is more effective than a dendritic cell therapy, which hasn’t been proven in clinical trials, or commercially approved (yet). (well other than Provenge and exwannabe’s favorite - Apceden)
So with this in mind, the BATON system was designed in 2016 to make a T-cell therapy. It uses the dendritic cells to load the T-cells with multiple neoantigens (rather than a single antigen like CAR-T’s) that are specific to each person’s tumor, and then cultures those activated T-cells. It’s a more natural, faster, and far less expensive method of manufacturing a T-cell treatment than engineering the T-cells, and it’s also potentially more effective and durable since it targets multiple antigens to prevent escape.
I think this system is really brilliant, and it could add value to Northwest Bio at some point down the road. Northwest Bio could develop a T-cell therapy, which could be used as a mono-therapy, or it could be combined with DCVax as a dendritic-cell vaccine shot and a T-cell infusion, or it could be combined with checkpoint inhibitors, etc., or the manufacturing system could be licensed.
Yep, I’ve discussed this BATON system several times, but you’re right, few seem to understand the significance or potential. (or maybe few read my posts :) )
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167176812
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=163095772
Excellent post dmb, and I completely agree. Many posters here seem to expect Northwest Bio to follow other small biotech’s established path, but as you explain, their situation is unique, and it requires some pioneering.
Great news, thanks Evaluate. That’s for the BATON system which cultures both dendritic cells and T-cells. Northwest Bio’s DCVax culturing process is a little different, but there’s aspects that this patent may cover in that process as well.
It will be interesting to see what becomes of this natural approach of using dendritic cells to introduce neoantigens to T-cells for a T-cell therapy, as opposed to engineering them.
flipper, I can’t explain Northwest Bio’s communications, but just because they didn’t spell it out in plain english, doesn’t mean that the milestone didn’t occur.
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My opinion is that the second milestone was insignificant and easily achievable, because it simply required performing the operations that the system was designed to do. During the validation of the Flaskworks system at Sawston, the Performance Qualification step requires documented verification that the equipment performs effectively and reproducibly, and is capable of performing consistently for multiple cycles and extended periods. So these qualification runs required manufacturing repeatedly for months. If there were any issues, (which I doubt) Advent has some highly qualified personnel in addition to the assistance of Shashi Murthy (who has a large incentive), and the technical staff who invented and tested the system, and conducted the study at Northeastern.
Déjà vu biosectinvestor? I’ve discussed ILAP with you before, but maybe at the time, you were focused on the FDA and RMAT. Some good info about other potential accelerated routes outside of the ILAP in that post as well.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=166762122
I think the second Flaskworks’ milestone was achieved flipper. Maybe you missed post 452662 or maybe you disagree.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=168259643
flipper, this is what the May 12, 2021 PR said:
So no they didn’t say that “they’d start running practice tests at the same time they predicted getting final imp certification at Sawston. “
The end of the 3rd quarter is the end of September. During the summer is before that (June, July, August).
And no, I did not say “the second EDEN milestone occurred last summer.”
I said “So I think that the second milestone was probably achieved some time late last year”
Late last year means 4th quarter (October, November, December).
Right, like I said, it’s not clearly stated. That’s why I also included the previous paragraph where it explains the Stock Consideration Agreement, and that the stock consideration may be recognized differently for tax and accounting purposes. (I included that section from the 10K below)
No, it’s not 1.5M shares for each milestone. The grand total is ~$2M worth of shares. ($1.95M for Shashi Murthy and $60k for Andrew Kozbial) The stock price was $1.40 on December 1, 2020 so that equates to the1.5M shares in total. The shares were issued, but they don’t all vest until the milestones are reached. It appears (to me) that when they are reached, NWBO recognizes them as a $0.5M research and development expense. One was recognized in 2020, and one was recognized in 2021.
No it’s not false. I’m not saying it’s exactly the same process, but it’s almost the same. The difference or “secret sauce” of the DCVax culturing protocols, is in the exact mixture of differentiation media (IL-4, GM-CSF, TNF-a etc.), the exact length of time for culturing, maturation, etc., but yes, it’s basically the same experiment. And it only required verification by “yield, phenotype and functional assay data.” (which is basically generic therapeutic dendritic cells) The second milestone does not require that EDEN produce the equivalent to DCVax, as defined by Northwest Bio’s assays, because that’s the third milestone.
That original EDEN culture cartridge that Advent almost certainly tested prior to the acquisition of Flaskworks, was supplied by Corning. The first milestone required finding a replacement manufacturer and a prototype of that EDEN cartridge. So the second milestone required Advent’s verification that the prototype from the new supplier performed the same as the one supplied by Corning.
The EDEN is basically the cell culturing system, which I believe is contained within the MicroDEN console which also houses the electronics to run the pumps and record the data of the culture process. The first generation MicroDEN device may not be suitable for the commercial process, so Advent may not be using that console.
The two EDEN culture chambers are the heart of the entire fluidic system of pumps, and fill and waste bottles. The real beauty of this EDEN cartridge is that the bottom is coated in polystyrene, which causes the monocytes to adhere to the bottom surface, and the bottom is also plasma treated, so it uses microfluidic properties, (Shashi Murthy’s specialty) which cause the fluids to flow in 8 channels, in a sort of clover pattern, to continually surround the cells with fresh media. It’s really a brilliant way to automate the culture process!
So it was not a small feat to find a new supplier to produce a prototype of the EDEN cartridge within 90 days of the Flaskworks’ acquisition. This first milestone was likely accomplished on time in November of 2020, since 1.5M shares were paid out on December 1, 2020 in accordance with the first milestone. (see 10K below)
The second milestone seems relatively easy to achieve as it was just proving that the system does what Flaskworks said it could do. Basically Advent just had to replicate the same experiments conducted at Northeastern University and St. Louis University to show the EDEN culture system could produce dendritic cells that were the same in number, phenotype, and induced T-cell proliferation etc., like DCVax. I think that this was probably the practice runs that should have occurred during the summer or fall of 2021 during/after the performance qualification stage. So I think that the second milestone was probably achieved some time late last year, although it’s not clearly stated in the recent 10K:
good to see you’re still around Umibe, and interesting to hear the background of those relationships.
hoffmann, your impressions are a pretty good summary, and seem fairly consistent with my own general view. My focus has been on manufacturing and unfortunately, not many clues were provided there. The extended wait for topline and journal publishing leads me to hope that parallel work is being done on a marketing application, and if that’s the case, then it makes sense to develop an automated commercial process to enable production soon after approval. I’ve been back and forth on this subject though, since too often we later discover that Northwest Bio is not as far along as we had hoped. Maybe we’ll get some answers soon.
Good job getting that “Swiss approval” in there ex. I know that’s one of your favorites. :)
First, it wasn’t LP who asserted it, the quote was by Alton Boynton. Second, the quote wasn’t “the world's first cancer vaccine” but instead, it was “the first company to reach the market with a personalized therapeutic vaccine for brain cancers,”
So the fact is, it’s not wrong.
lol. I rarely read his posts, but it will be satisfying when that joker is proven wrong.
marz, my guess is that the validation work addressed issues raised by the inspectors, but it’s anyone’s guess. There have been guidances issued by regulators that updated Process Validation since manufacturing for the clinical trial concluded. Part of the revisions involved methods to assure continued operational quality through continuous verification. Regulators now recognize that good process control, monitoring, and process verification through real-time-release testing can assure that a product can be found acceptable prior to the conventional quality control measure of final product testing. The agencies expect all legacy processes to be validated, and there may have been some gaps in the new SOP’s.
Advent didn’t begin manufacturing until February because they had to perform some validation work after licensing. From the 10K:
Actually, you’re pretty close Sojourner. The available shares for sale was around 25 million at the end of Q2, and increased to around 30 million at the end of Q3 and increased further by the end of the year to about 63 million. And subsequent to the end of the year, an additional 16 million warrants and options were put under block suspension, until up to May 15, so the current number may be close to 80 million.
948,400 Common Stock outstanding as of December 31, 2021
225,469 Warrants
304,847 Options
————————
1,478,716 Total Common Stock, Warrants, and Options Outstanding
- 342,000 Warrants and Options suspended (102 warrants + 240 options)
———————
1,136,716 Total Common Stock, Warrants, and Options outstanding excluding suspended Warrants and Options
———————
———————
1,200,000 Share Authorization Limit
-1,136,716
———————-
63,284 Shares Available under the limit
thanks senti, that’s the PR that I was looking for, but I thought it was after 2013 when those patents were issued and manufacturing protocols were transferred to London and Germany. Okay then I doubt those manufacturing changes were implemented for the trial.
I’ll take your educated word about the TFF work for DCVax-L, but I’m not sure that they would find it necessary to confirm that the work has been completed though. I think it’s highly likely that these manufacturing improvements have been implemented outside of the trial in the London facility manufacturing for the “specials” program, and I think Dr Ashkan could provide the Real World Evidence to support a regulatory approval. There’s a phrase that Northwest Bio said in regulatory filings years ago that has stuck with me:
“We believe the most important value of early access programs lies in the regulatory validation involved, and the invaluable opportunity to practice for commercialization outside of clinical trials and before actual commercialization.The opportunity for some early revenues is also encouraging, but in our view is secondary.”
IkeEsq, thanks for this, and your many sensible posts. You’re a voice of reason here and I appreciate your perspective.
Thanks senti, but I was talking about ATLnsiders estimate for Flaskworks potential production capacity based on 10X the capacity of the manual manufacturing method, that may have been in a Flaskworks PR or an article about the system.
Interestingly though, I dug that same PR out not too long ago and reposted it too. And now that you brought it up again, and we have recently discussed this and the TFF potential manufacturing changes during the trial, I have a lingering question about the timing of the change in the trial from phase II to phase III. Do you know when that occurred as it relates to these two significant manufacturing changes? Was it in 2014? Usually, you would not implement manufacturing changes (unless it’s safety related) during one phase of the trial as that could potentially impact the results, so manufacturing changes are normally implemented after one phase has been completed and before another phase is initiated (or before commercialization).
I have thought that if those manufacturing changes were made, it would have occurred in this trial between those phases, and maybe that’s part of the reason why some refer to, and are watching, the last hundred patients or so. This has probably been discussed I’m sure, and I understand one reason is due to the additional 17 treated patients in the treatment arm vs the placebo arm. One question that I’ve had is if one or both of the manufacturing changes were made, along with the sicker patients that were enrolled at the end of the trial, if that is what potentially forced the imbalance of the two arms at the end of the trial. What do you think?
That’s pretty funny ATLnsider, thanks. That phrase has been gaining some traction lately. Maybe it’ll be trending soon . . .
100% senti, a significant portion of that Sawston cold storage will be used for Northwest Bio’s purposes to store tumor tissue and DCVax finished doses. The cold storage can be shared since there’s virtually no risk of cross contamination. You probably know that Advent has an ancillary services agreement with Northwest Bio which is similar the Cognate ancillary agreement which includes: cryopreservation and storage services, shipping, distribution and logistics services, scheduling and software services, documentation and record keeping services, and other miscellaneous services. The logistics companies (CryoPDP/Cryoport, Biolife Solutions) that cell therapy manufacturers and CDMO’s contract with, have also broadened their service offerings to include cold storage, so Advent could potentially use some of that capacity in the more distant future if Sawston capacity is constrained.
ATLnsider, I think there’s many ways to guesstimate the potential production capacity for Flaskworks automation, so until we get more information, it’s really anyone’s guess, and you could be right. Our estimates were really not that far apart using different methods, but that 16,000 number that I threw out was just theoretic, and I wasn’t trying to be accurate at this point because there are too many unknowns. Perhaps my post was a long winded way of saying that I think Sawston is a relatively large facility, with plenty of capacity for Advent to manufacture DCVax for both the UK and EU, and as flipper said, there’s also room for Advent to manufacture for other clients using the high-grade clean rooms, that for the most part, Northwest Bio won’t require. Plus, there’s potentially a way to scale it to the masses when that time comes.
I’ve seen that 10X manual process capacity estimate here before, and to be honest, I don’t know where it came from. Is that taken from Corning’s brochure for the Flaskworks’ MicroDEN system? That it’s supposedly 10X more efficient or something, so somehow it will have 10X the production capacity? I personally don’t think that’s a useful way to analyze Flaskworks potential production capacity because the open manual processes, workflows, and clean room requirements are so different than for the automated, closed processes.
The automated workflow manufacturing process for CAR-T’s is much more similar to the automated workflow process that I think DCVax will have. The first step for both is cell isolation, (with CAR-T’s, the T-cells are separated from the other cells in the leukapheresis material instead of the dendritic cells) and although the CAR-T’s go through an extra process of engineering the T-cells, but the DCVax dendritic cells don’t, otherwise the rest of the manufacturing process involves culturing, washing, filling into dosing containers, and cryopreserving, which is all fairly similar. So, because it's an established autologous cell therapy, that will likely use a similar closed, automated production process as DCVax, it seems (to me) to be a more tangible way to compare and estimate.
To be realistic though, and put these projections into perspective; it’s been almost 5 years since Yescarta was approved, and Kite is still only producing at half of that projected capacity level. Although I anticipate that DCVax will ramp much more quickly than Yescarta, it’s still an expensive, brand-new cell therapy treatment with insurance reimbursement hurdles, complicated logistics, and new hospital protocols to establish, etc., so even though I project that potential capacity, I think the ability to manufacture DCVax in these larger quantities may not be as necessary as rapidly as many here seem to expect.
Agree flipper, manual production will be history, but as I said before, I think there’s a reason that Northwest Bio gives an annual figure for it. And of course cold storage is critical regardless of the manufacturing method. The tumor tissue is shipped and stored in the -20C to -80C range, while the finished doses are cryopreserved and stored in the colder > -194C cryostorage.
I’m not sure if people understand how large the Sawston facility actually is, so I’ll throw some comparability numbers out there. Sawston is roughly double the size of Kite’s 44,000 square foot El Segundo CAR-T manufacturing facility, which Kite estimates is large enough to produce about 4,000 personalized cell therapy treatments annually. The shell size alone shouldn’t be used to compare with potential DCVax manufacturing capability, because this doesn’t account for the difference in manufacturing time or potential space utilization.
It seems reasonable to think that with process optimization using Flaskworks and other automated processes, DCVax-L manufacture time may be reduced from 8 days to 7 days, which is less than half the manufacturing time of Yescarta’s ~16 days. So given that Sawston is double the size and it takes half the time to manufacture DCVax, then theoretically, Sawston should be able to produce 4X Kite’s number, or 16,000 treatments annually using the whole Sawston facility, or the same number of treatments using 1/4 the space. (4,000 treatments using 11,000 square feet) But there’s more.
CAR-T manufacturers use individual all-in-one, end-to-end manufacturing work stations, which isn’t the most efficient use of space, as it ties up each individual work station during the long culturing step. If the Flaskworks system has one culture chamber, then the manufacturing capability would be approximately the same per space utilized. However, with Flaskworks system development, it’s conceivable that, by using larger media fill and waste tanks, and adding additional culture chambers and perfusion pumps, it could produce multiples of that in basically the same footprint. So by adding 10 culture chambers to each system for example, each manufacturing run could produce 10X the number of treatments in basically the same floor space. This might be what Michael Bigger was taking about when he said “cleanroom disruption.”
And sometimes good enough is unacceptable. Anyone who has worked on under-resourced projects knows that when safety and quality can not be compromised, it’s usually the timeline that suffers.
I agree with this post as well. By the way Viking, I’ve read some of your market commentary, and think it’s pretty spot on.
I don’t think Linda Powers is working off a term sheet per se, but she certainly understands how to add value to the company, and I anticipate the following to occur in the next year or so timeframe:
|X| Licensed manufacturing facility
| | Clinical trial data that is approvable by regulators and accepted by medical community as a new standard of care
| | Improved capital structure and listing on major stock exchange
| | Regulatory approval
| | Licensed manufacturing facility for commercial production
| | . . .
I don’t think management is playing games Bob, but I do agree in general, that “independent” boards are mostly a farce, and small shareholders have little say in these matters. The temporary option and warrant suspensions are in place to keep the potential exercises below the number of authorized shares. While some posters seem to think management has a complete disregard for shareholders, I think management is well aware of shareholder angst, and has chosen the least undesirable alternative. Letting the options expire seems unrealistic since there would have been other options like increasing the authorized limit, which would likely not be a popular choice to shareholders who have been kept waiting for clinical trial results, and the other option is a reverse split, which is an even less popular option at this point. It does seem clear to me that the runway is getting pretty short, so one of these other alternatives will have to occur fairly soon. The annual shareholder meeting this year should be pretty interesting.