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I don’t think you are considering the circumstances.
First, MHRA prioritizes therapies for unmet medical needs indications that are life
Threatening.
Second, NWBO applied under the MHRA’s rapid 150-day review pathway, which the agency has established for new medicines for serious unmet medical needs.
Third, the changes at MHRA go into effect March 1. NWBO will be at or near the end of 80 day phase I in March.
DJPele found the news letter. I just read the link.
For NWBO at this time, this seems like the most relevant section, which goes into effect March 1, 2024.
This is a big deal.
Deadline for Second Amended complaint filing appears to be March 15, 2024. That’s two weeks from this coming Friday.
Of course 10K may come out this coming Friday. (This week)
Why do you think I would be “chagrined” if MAA approval happens sooner than I think?
Good Point PD. People should select “show more” in the tweet/x below.
#dcvax $nwbo #gbm
— Peter Davis (@peter_brit) February 26, 2024
With the article mentioned, on the use of external control cohorts in Pediatric Brain tumor clinical trials, it should also be noted that not only did the MHRA fast track the approval of #nwbo's Pediatric Investigation Plan (PIP) - pre-requisite for… https://t.co/2c20esPhZA
Recent movement.
1. Combination patent application in Europe to be granted, includes both DCVax-l (lysate pulsed) and/or DCVax-Direct (partial maturation) with checkpoint inhibitors.
2. Wednesday will mark 70 days since MAA was filed.
3. MHRA and FDA looking at further cooperation.
4. Nature Journal article on DC/poly-iclc combination study nearing publication. Primary completion date for study occurred nearly thirty days ago.
5. Active negotiations with other parties for combination trials going on for over a year, awaiting MAA to be “cemented.”
6. Large pharma struggling to adapt to upcoming patent cliffs.
7. Cohen/Milstein/Posner about to file second amended complaint, and with it, formulaic method to arrive at loss causation.
8. Flaskworks (aka: NWBO) continues IP momentum.
9. Advent hiring head of production to hire team to facilitate biotherapeutic production for clinical use. (Direct?)
10. FDA pursuing Promising Pathways.
What may be sooner than I think?
Why would that be to my chagrin?
“Cemented” within about 80 days and/or March CHM meeting, imo, dependent on when validation was confirmed. It appears it was confirmed on or before January 4, 2024.
Since cement did not mean validation, imo, it must mean a (hoped for) manageable phase I directive, otherwise she would have said upon approval.
Cement, in this context, typically means to make stronger. Stronger would be at some interim stage. Stronger would mean whatever they ask for at 80/CHM is doable within the 150 day (+ 60 day clock off if necessary), imo. Approval does not make an MAA “stronger,” it instead completes its function.
You argue:
“AMRN girls” — Exwannabe
Unless I’m missing something, in today’s world, this phrase comes across as misogynistic and patriarchal.
NWBIO Dec 21, 2023
CHM meeting.
I think it’s 60 days after quarter ends for the yearly 10 k.
Yeah, it’s just a first draft prototype🤓
Maybe something like this?
The first point = MHRA approval and manual production
The second point = additional marketing applications and commercial closed system automation unit being tested in parallel with manual method.
The third point = Other regulator approvals contemporaneous with commercial closed system automated approval.
The Fourth point = Global saturation
Memory lane. Here was my first post on Ihub NWBO message board.
Good Heavens man. Read some basic biology regarding the adaptive immune system. Maybe then you’ll understand why DCVax-l is at once the safest yet very broad spectrum.
If you want danger, look for car-t cells which are engineered to kill healthy cells as well.
Wrong. The MHRA were first to approve the Covid vaccine and CRSPR therapy. I listened to one of their meetings online, and they still expect to approve 60% of therapies outside of the IRP process.
You’re right about one thing, there is no comparison. DCVax-l’s broad spectrum (n = hundreds to over a thousand different t-cell clones proliferating to make millions to billions of cloned cytotoxic t-cells) targeting solution dwarfs Moderna’s limited artificially (n = 34) selected target Solution.
Perhaps you read my dialogue with ChatGPT on B cells a couple weeks ago. Here is a combination of ChatGPT answers to my questions on that topic. Its redundant at times, because below I skipped putting in my follow up questions, so it reads a bit repetitive but very informative.
B cells learn which antibodies to produce through a process called affinity maturation. Initially, when dendritic cells present antigens to T cells, B cells with receptors that can recognize those antigens are activated. These activated B cells then undergo clonal expansion and differentiation into plasma cells, which produce antibodies specific to the presented antigens.
During affinity maturation, B cells undergo somatic hypermutation, a process where the DNA encoding the antibody variable regions undergoes random mutations. B cells with mutations that result in higher affinity for the antigen are positively selected, while those with lower affinity are negatively selected. This process allows B cells to produce antibodies with higher affinity for the specific cancer antigens (originally) presented by dendritic cells (to the t-cells), leading to a more effective immune response against cancer.
Dendritic cells indirectly activate B cells with appropriate receptors through a process called antigen presentation. When dendritic cells encounter cancer antigens, they internalize and process these antigens. Then, they present small fragments of these antigens, called peptides, on their cell surface using molecules called major histocompatibility complex (MHC) molecules.
T cells constantly survey these MHC-peptide complexes presented by dendritic cells. If a T cell recognizes a cancer antigen presented by a dendritic cell, it becomes activated. Once activated, the T cell releases signaling molecules, such as cytokines, that can stimulate nearby B cells. These cytokines can trigger B cell activation, leading to their proliferation and differentiation into plasma cells, which produce antibodies specific to the cancer antigens. So, dendritic cells indirectly activate B cells with appropriate receptors by presenting cancer antigens to T cells, which then release signals to stimulate B cell activation.
The antibodies formed through this process contribute to a more effective response against cancer in several ways:
1. **Direct targeting:** Antibodies can directly bind to cancer cells, marking them for destruction by other immune cells such as macrophages and natural killer cells through a process called antibody-dependent cellular cytotoxicity (ADCC) or complement-mediated cytotoxicity.
2. **Neutralization of cancer-promoting factors:** Antibodies can bind to cancer-promoting factors such as growth factors or receptors, preventing them from interacting with their targets and inhibiting cancer cell proliferation and survival.
3. **Enhancement of antigen presentation:** Antibodies can bind to cancer antigens, forming immune complexes that are more efficiently recognized and processed by dendritic cells. This enhances the presentation of cancer antigens to T cells, leading to a stronger T cell-mediated immune response against cancer.
4. **Recruitment of other immune cells:** Antibodies can recruit other immune cells, such as macrophages and neutrophils, to the tumor site through the activation of complement or Fc receptors, further enhancing the immune response against cancer.
Overall, the antibodies produced through the activation of B cells by dendritic cells play a crucial role in coordinating and amplifying the immune response against cancer, leading to more effective elimination of cancer cells.
Additionally, during affinity maturation, B cells undergo somatic hypermutation, resulting in the generation of B cells with higher affinity for the cancer antigens. These B cells, known as memory B cells, have a longer lifespan and remain in circulation even after the initial immune response subsides.
The presence of memory B cells ensures a faster and more robust immune response upon re-exposure to the same cancer antigens in the future. If cancer cells reappear, memory B cells can quickly differentiate into antibody-producing plasma cells, leading to a rapid and specific antibody response that contributes to the elimination of cancer cells. Thus, B cell memory formed through this process provides long-term immunity against cancer recurrence.
🔑I guess what I might try to elucidate more fully tomorrow is this:
During a robust immune response, the body can sometimes produce billions of cytotoxic t-cells. If the immune response, even if it’s not in the billions, is elicited by DCVax-l, those millions or billions of cytotoxic t-cells are extremely diverse. Up to 1200 different t-cell clone types (making up millions or even billions of cytotoxic t-cells) targeting up to hundreds of antigens on various tumor cells — thus reducing the chance of escape.
I hope this helps bring home further the unparalleled broad spectrum approach utilized by NWBO.
Modern’a melanoma vaccine goes after up to 34 artificially selected antigen targets, and it adds an otherwise unnecessary step. DCVax-l can elicit a broad spectrum (as many as 1200 different t-cell clones) of different t-cells to go after hundreds of antigen targets.
I gotta say, intuitively, I thought this might be the case, but pragmatically, DCVax-l directed t-cell clonal expansion is an astounding and exponentially powerful phenomenon.
Some of you may be questioning, like I was, how 600 different expressed antigens could possibly lead to 800 then 1200 different types of t-cell clones.
I asked that of ChatGPT (a poorman’s substitute for Dr.Prins or Dr.Bosch).
Here is what it said.
The diversity in T cell clones arises from their ability to recognize different epitopes of the expressed antigens. Even though there are 600 different peptides (tumor targets) presented by dendritic cells, each (different) T cell clone focuses on a particular and distinct target (epitope) within those peptides. So, multiple T cell clones can recognize different parts of the same expressed antigens, leading to the expansion of a diverse pool of T cells. 🔑
I’ve not done one, but from what I gather, the primary working document turned in with the MAA is normally less than a thousand pages, and references and footnotes portions of the other 1.7 million page (sections) throughout.
Specialist reviewers do not read all 1.7 million pages, but they certainly read the primary document and more than spot check the reference data.
I just select the text and use the feature, like the “” feature, to the left of my message. I’m normally on a personal device.
The “only way you could see” is to stop getting reimbursed by opposition forces.
From a different angle, whales realize that DCVax-l’s proprietary rights, excluding their recent combination patents abroad, begin at the moment of first approval as a biologic.
In other words, market approval not only means a valid, profitable and expandable treatment platform, but it also confirms and initiates the decade long clock for biologic exclusivity. “Show me” whales know the importance of the first marketing approval.
You can’t even distill the long interview you watched. Just yap yap yap.
Northwest Biotherapeutics, December 21, 2023. 🔗
As the Company previously reported, proteomic studies have demonstrated that a single tumor lysate sample contained tens of thousands of different peptides and, out of this pool, the dendritic cells selected, processed and presented over 600 different peptides (tumor targets) to T cells. T cell studies (TCR sequencing and T cell clonal expansion assays) analyzing the breadth and strength of T cell response following DCVax-L treatment have found extensive responses, including clonal expansion of up to 800 T cell clones at month 4 and up to 1200 T cell clones at month 8 in the samples studied. Each T cell clone focuses on a particular and distinct target. In individuals not being treated with the vaccine, only 2 – 20 new T cells clones are seen between month 4 and month 8.
The results of these proteomic, T cell and other studies provide support for what the Company believes to be the mechanism of action of DCVax-L: i.e., mobilizing a broad spectrum and strong de novo T cell response that addresses the extensive heterogeneity of GBM and overcomes the immunosuppressive microenvironment around the tumor.
The Company believes that this mechanism of action will be applicable for most types of solid tumors.
Please consider carefully reading (again) the post I am responding to this morning.
Here is the 🔗
Robot droid, I did not know you could feel emotions like sadness. Well, as a human, let me express that this to shall pass. Particularly when you understand companies don’t announce a PR every day. Good luck with your emotions.
You are right. It is helpful to read multiple times. Thank you for the highlights. I continue to believe the proteomics findings will/is change/changing the entire industry. The ramifications are stunning and demonstrate why DCVax is the keystone. Best wishes to patients.
Get out of your mom’s basement. Get some vitamin D for God’s sake.
You realize your heroes, both Exwannabe and LC, have conceded DCVax-l is based upon strong solid science?
It was voted for twice. They’ll vote for it again. Plaintiffs would resolve if company being sold or lucrative combos/partnerships, or simply approval, imo. Plaintiffs own like 120,000 shares combined, and they would see management actually did their job, and in fact plaintiffs would realize they’d (aka plaintiffs) be the ones responsible for diluting if they didn’t resolve matters.