Replies to post #805392 on NorthWest Biotherapeutics Inc (NWBO)

[Zadie420]

The construction of two large C- labs should take less than6 months per previous Q report to complete. Not 1 year.

[manibiotech]

Agree with your points Also agree that it is highly unlikely they will file to FDA in 26 in my opinion . That statement was very non specific and seemed more to appease the shareholders than having a concrete plan for FDA. 

[maverick_1]

Thank you HyperOpia for your thought re 2025 ASM

One notable EXCEPTION
But as we announced in our more recent filings, and I think we first announced it maybe late last year, anyway earlier this year, that we had developed a plan for a simplified C lab to build one on a simplified basis in a different location. It actually happens to be adjacent to the quarantine storage and loading docks, where far less infrastructure work has to be done, and it cut to less than half the cost of the design of the original C lab.

That’s the one where we mentioned in our most recent quarterly report, Q3, that the contractor has already been selected and engaged, already been on site doing the prep work of the site, and we currently anticipate that the physical construction work would get underway at some point by the end of January for that, and then would be around a six-month timeframe to get finished for that.
From SLAVE1's STICKY transcription

DIFFERENT STROKES for DIFFERENT FOLKS

[hyperopia]

Thoughts on the Shareholder Meeting: Part 2

On clinical trials:

With all the focus on its lead program DCVax-L, some may have forgotten this, but Northwest Bio actually has a significant pipeline. This includes not only DCVax-L and DCVax-Direct, but also an extensive pipeline in-licensed from Dr. Pavel Kalinski’s work with dendritic cells for over twenty years at the University of Pittsburgh and Roswell Park Comprehensive Cancer Center.

In the decade since the initial trials were conducted, much general knowledge and familiarity has been gained by scientists about immune signaling, and in the biotech industry with manufacturing cell and gene therapy products. Additional clinical evidence has been gathered over the past decade that both DCVax and Dr. Kalinski’s dendritic cell therapies can be safely combined with various other agents like double stranded RNAs, (Poly ICLC & Ampligen) and checkpoint inhibitors that can significantly increase their potency and improve immune responses which have led to significantly improved survival results. Northwest Bio is now finally ready to begin the next generation of clinical trials with the knowledge gained since the first generation of trials over a decade ago and continue testing various combinations, and their sequencing and timing for the best results.

Over the past couple of years while Northwest Bio has been supporting its marketing application in the UK, they have also been quietly preparing for numerous clinical trials; DCVax-L pediatric trial for brain cancer in the UK, DCVax-Direct and DCVax-DR (enhanced version of DCVax-Direct), and at least two trials for therapies in the Roswell Park portfolio. We know from their SEC filings that the next set of clinical trials have been designed to be compact and streamlined, using Simon’s two-stage designs to start small and then expand if encouraging results are seen, and will focus on tumor response endpoints which have a short timeframe and do not require control arms.

At the shareholder meeting Linda Powers did not go into as much detail on these trials as most of us would have liked, but some new information was given.


Pediatric Trial

The pediatric trial for DCVax-L wasn’t discussed at the shareholder meeting, but the last official information that we have about it was from the Annual Report in March which stated that the clinicians requested substantial changes to the original trial design which had been previously approved by the MHRA, so a new trial was designed and agreed to by the clinicians, and the company intended to obtain MHRA approval of the new design and move forward with the trial “in due course.”

DCVax-Direct & DCVax-DR

Over the past two years, Advent has transferred all manufacturing technology protocols for DCVax-Direct (which was manufactured by Cognate in Memphis US) to Advent at Sawston UK, determined which technology will be used in the first step of the manufacturing process (separating the monocytes from the rest of the immune cells in the leukapheresis material) either using the original outdated proprietary tangential flow filtration (TFF) system or a newer commercial system (I’m guessing new system), determined which ingredient(s) will be used to replace BCG (which is now scarce), developed new SOPs for the the new version DCVax-DR, and have written the Chemistry and Manufacturing Control (CMC) sections for the IND package. Advent has also performed mechanism of action studies, which will be helpful in the phase 2/3 trials and is required when applying for regulatory approval. (reminder - MOA studies were not performed in the Phase 1 DCVax-Direct trial, and were performed long after the DCVax-L trial completed which held up filing for DCVax-L approval)

Importantly, they have also found a new source of BCG and have maintained the original formula (GM-CSF, BCG+IFN ?) which means they have successfully performed all the engineering comparison runs, validations, and have met the original final release specifications in the transfer to Sawston. Their quarterly reports have revealed that they intend to trial both versions. (possibly as separate arms, and probably for compassionate use in multiple cancers)

During the shareholder meeting, Linda revealed that the indication has been selected for the next, Phase II DCVax-Direct trials, but only hinted that it is for a “below the neck cancer,” and that the lead institutions in both the US and UK are prepared and excited. Another hint, that “it is a particularly bad cancer for patients and that something new and different is needed,” leads me to speculate that the indication is pancreatic cancer.

This is an extremely aggressive cancer with few treatment options but Northwest Bio did have encouraging results in the phase I trial, and has anecdotal evidence that DCVax-Direct may finally move the needle in this deadly cancer too. Most of us remember that a stage 4 pancreatic cancer patient (Alan Butler from National Geographic) was treated with DCVax-Direct in 2014 and is still alive over a decade later. National Geographic featured him in a special on cancer and Northwest Bio was ridiculed in some media publications for “exploiting” him, and a small firestorm was created over this at MD Anderson.

Despite the fact that the phase 1 trial was a first-in-man feasibility study and it had many limitations, like only taking the sickest patients who had exhausted other treatment options, testing several dose levels, injecting a single tumor, and Cognate had several manufacturing failures, the results were encouraging, and some valuable knowledge was acquired, which will be applied in the next phase 2/3 trials.

On the subject of manufacturing, there have been some false AI postings on this board that DCVax-Direct uses the Flaskworks system. As I have posted before, DCVax-Direct does not use the Flaskworks system. It is manufactured in a closed system which uses disposable culture bags, not flasks, in order to delay activation and only partially mature the dendritic cells. This difference is critically important.

In manufacturing DCVax-L, when loaded into the Flaskworks sytem, the monocytes adhere to the bottom of the polystyrene cartridge which initiates the activation process and then later antigens from the tumor tissue are added to the cartridge to educate the dendritic cells. However, with DCVax-Direct, it is necessary to delay the activation in order for the dendritic cells to take up the antigens in the body from dead or dying tumor cells. (immature dendritic cells have the ability to take up antigens but fully mature dendritic cells do not) In the bagged system, the monocytes are cultured in suspension and do not adhere to the surface, which allows Advent to control the activation process so the dendritic cells can be optimally activated. The partially activated dendritic cells in DCVax-Direct retain the capability to take up antigens in-vitro but are irrevocably committed to full maturation.

Dr. Kalinski’s Therapies from Roswell Park