Replies to post #417302 on NorthWest Biotherapeutics Inc (NWBO)

[jdheart101]

I’m starting to think that Nwbo success will come from Direct and we will never know the outcome of L. Think about the release the P3 if it has technical faults making the trial faulty but the science is good nwbo would either and die if they keep it under wraps nwbo can continue on and wait for direct a better trial and improved therapy, why else would they be doing what they are doing

[sukus]

Great post Flipper. Good reading on Saturday morning. :)

“The wait for DCVax-l has been intolerable, but it is now set up to succeed on efficacy, economic manufacturing and against competition like never before. “

[jdheart101]

Just read it but I will disagree on the premise that there is something wrong with the L trial , technically wrong that needs to be redone but they know the science is good so they are not releasing TLD and the paper will support the science but the trial due to something technically failed, but nwbo is prolonging all this to get Direct news which will be a success ….hopefully

[extrooper]

The beauty is, your summary is based on facts.

[beachhyena]

A beautiful dawn is fast approaching when news of the future of cancer therapy though immunotherapy will provide people across this world real hope that finally science is making inroads into defeating this devastating disease that has afflicted so many loved ones across the ages.

[KIPK]

Nicely done flipper

Very long NWBO

[CaptainObvious]

Great post, flip.

[HappyLibrarian]

Presumably if you change the definition of GBM you reduce the number of customers.

[Sojourner55]

Great post Flipper!

[sentiment_stocks]

As horrendous as this long wait has been, there have also been, as you point out, developments in immunotherapy, GBM, in the manufacturing, and even with the regulatory agencies that will make the runway forward much less bumpy than it would have been five or more years ago.

[Ready4Nxt]

Flipper, I really appreciate the time you take to support this board.

[spidaman]

Flipper44 your response was like poetry. You are one of the reasons I invested in NWBO and have been a share holder for years. I appreciate all that you do for this board. Good luck to us all.

[Pharmboy46]

I can’t believe I missed this post- it’s an epic post- should be stickied!

[skitahoe]

Flipper,

I very much appreciate what you've said about DCVax-Direct, I do have one question. I gather it has been improved, I'm just questioning whether the regulators will allow it to go directly into a Phase 2/3, or if they'll insist on a Phase 1 with the improved vaccine.

I agree with you that getting DCVax-L approved, so no questions will be asked about that is smart at this late point in it's development. I don't think it would have mattered 5 years ago, but we're so close that it's better to wait. I would hope that DCVax-Direct can initially be made using the FlaskWork device, that would eliminate all discussion about it's use in making the product post approval.

I would expect that if we establish a BP partner that development of DCVax-Direct could be substantially faster than without them as they should be able to gear up for a more aggressive trial, use far more clinical sites to gather data faster. No doubt, remaining independent NWBO should be able to fund such a trial with dilutive funding, but staffing would take more time than if we have the resources from a BP partner available to us.

Thanks for all your efforts,

Gary

[Doc logic]

flipper44,

Nicely done! Great summary and with the old vim and vigor in defense of it as you fire up the longs chugging along up Heartbreak Hill in the home stretch. Best wishes.

[Horseb4CarT]

Nice job Flipper!!!

It’s so close I can smell dcvax success!

[1sdestiny]

Great post. Very informative. Many thanks for your analysis.

[eagle8]

Great post flipper.
Thanks.

GLTU

[WojD40]

The Cool, Cool River...nice.

Flipper, in the five years I've been reading your posts I don't think I remember you in this good a mood. Fingers crossed it's an omen.

[The Danish Dude]

Lovely confidence piece flipper!!!

[pgsd]

Thanks flipper, excellent post. GLTA

[Mionaer1]

Great Post. Thanks Flipper.

[Lykiri]

Great post. Very informative. Many thanks for your analysis, flipper44!

[MI Dendream]

One rule of thumb that is generally followed is that you do not leave open a trial when you submit your package to FDA or they may tell you that they prefer to wait and get results from that active trial first. When your package is ready, you close the box, seal it and have it postmarked and signed for upon delivery.

I did not connect Direct to L in that way but do not disagree with that logic. Thanks, Flipper. It may have even been made clear to them that if you feel you are entitled to an accelerated path to proof with B, you connect the dots yourself to A and already have in our minds. It is a possibility and one that would likely be delivered in a way that does not allow you to publicly speak for FDA. This actually could work in your favor as you collect patents on everything. A good testing method to ensure as much uniformity as possible should be as complex and tightly controlled, validated, and assured before shipping not only to assure safety and efficacy, but also to protect technology. That too can be perfected in the meantime.

Looking at the glass and the water within is a better practice than looking at what is missing. Thinking about Phaciltate just tweeks me. There actually is a right way and wrong way to do some things and do them well. BUT there is a whole lot of water in that there glass.

Your possible explanation for what could go down as far as SNO also helps.

[Smokey21]

Flipper, that Patent document is a treasure trove of information about DCVAX (both L and Direct), although it is focused on DIRECT. There are many hidden nuggets in it. To me, this paragraph is the holy grail of why it works so well and can even be tuned to be better in future iterations:

Fully mature dendritic cells are not preferred for the present methods and compositions because once they are fully mature the cells no longer efficiently process antigen. Further, immature dendritic cells as used in prior methods which have not been induced to begin maturation are not desired because the immunosuppressive environment typically found within a tumor, or in the tissue surrounding a tumor, include substantial concentrations of cytokines known to prevent the processing of antigen by immature dendritic cells. In the present disclosure, partial maturation and optimal activation of the immature dendritic cells down regulates cytokine receptors on the surface of the cell rendering them less sensitive or responsive to any immunosuppressive effects of cytokines present in the intratumoral space, or surrounding tissue, and provides for cells that can efficiently uptake and process antigens present within the intratumoral space or surrounding tissue. The dendritic cells take up and process substantial amounts of tumor antigen from apoptotic and dying tumor cells found within the intratumoral space or in the surrounding tissue. Once the administered partially matured and optimally activated dendritic cells have effectively matured within the intratumoral space as measured by, for example, the expression of the chemokine receptor CCR7, the dendritic cells migrate to the lymph nodes where the dendritic cells now presenting antigen will contact T cells, particularly naive T cells, to up regulate the immune response to any tumor antigens presented by the dendritic cells.

[Troymister]

Terrific summary.

[erik007tc]

Excellent! Buying more tomorrow :)))

[scotty3371]

Dendreon did not show the same efficacy he hope that dcvax is about to show.

Thanks flipper, I will be writing you in on the next ceo election.

406 days since data lock.

[learningcurve2020]

Just imagine if Powers had held quarterly cc's explaining all this to her shareholders. But no, instead we've got people on this board constantly calling the shots and getting it mostly wrong for over a decade. Hey, at least that keeps Powers in the free and clear able to pursue other endeavors. See how that works?

[Basin Street Blues]

Great narrative , thanks

[Know-Fear]

A couple of notes: Direct is partially automated and as we know it has been for a while. There is a lot of art inherently in living cell production. As an investor I would like to think NWBO also has some trade secret art relative to optimization. Automation is a good way to protect trade secret art if it can be incorporated into the firmware for production. That stated I like the revised patent language better than the original language for the claim on the maturation. As ex pointed out the original claim was denied my response to him is pasted below.

Knew the clarification was coming…..
The prosecution of Direct patent took some time, question of efficacy aside, the allowance of about 16 accomplishes the same thing as 12 to 20. Assuming that is key to the secret sauce……

Assuming there is value in this patent the fact that the prosecution took some time and the original claim was denied will likely signal that this patent is vulnerable and could be challenged and possibly invalidated in court. That stated in behooves NWBO to have all their ducks in a row and may explain the protracted delay in many areas.
As an aside there is a patent battle going on now between Moderna and and one of your favorite organizations the NIH over patents for the mRNA vaccine produced by Moderna. Which happens to be the most effective Covid vaccine to date. And an example of what happens when big $$$‘s are on the line.

Also hope our experience with Covid will in time help us get over our trepidation around mRNA vaccines. Because they are the future and at some point our flu vaccines will likely be mRNA vaccines.

[Dr Bala]

Excellent stuff. Thanks.

[abc1212]

Great post Flipper

The wait for DCVax-l has been intolerable, but it is now set up to succeed on efficacy, economic manufacturing and against competition like never before.

Many thanks

[Nick119]

Flip, you have made some of the most logical, concise, well explained arguments I've have ever read anywhere, period. Thank you for being you.

[ATLnsider]

Well stated flipper44

[barnstormer]

Nicely done Flipper.

[Bigmahalo]

Great Post Flipper44!