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Thank you again Doc logic for another solid answer. I agree that
a post approval+ partnership would constitute a dike that would effectively
inhibit the abilities of NWBO's enemies from interfering with an
increasing SP that would normally follow such positive news.
Absent a partnership, I very much hope that by approval time, NWBO
will have the Edens system in full operation and will let us know the
number of patients they would be able to treat going forward.
Any positive news before or shortly after approval, such as an MTD,
Combo trial results or the Nature article, would be icing on the cake.
Let me also not forget the very positive effects of an MAA submission
to additional regulators.
With respect to 20-30 days, IMHO only #10 is a virtual certainty
and #4 is a strong probability but I am very doubtful about the
rest, except for #7 (an outside the box possibility).
I must say Doc logic that I am somewhat confused about your opinion that the
SP is going to be crushed up to or even after MHRA approval? I also do expect the SP
to be increasingly suppressed up to approval and perhaps somewhat beyond approval
but I doubt that this can last for more than several months. What interests me to know
is your projected time as to how long the shorts and manipulators are likely to have the
upper hand and the reasons for your estimates.
Even without intervening post-approval positive events such as a partnership or a MTD denial,
the UK approval itself may have a very positive effect and that may start several months after approval
simply because of the increasing profits obtained from insured UK patients. The question then is for
how long can the shorts and manipulators retain their effectiveness in suppressing the SP.
I hope you are right Aperture but the end of March is only
days after the CHM meeting and we may have to wait a few
more months until MHRA approval before we experience
a steadily increasing SP.
We may have a few good news items (Nature publication, UCLA
combo trial results, a denied MTD)) in the next two months and
that may temporarily raise the SP but I believe that the real and
more stable SP increase will begin with MHRA approval.
[quote NWBO is selling shares to fund ongoing operations. That's what pre- revenue companies do. That will change soon on DCVax-L approval][/quote]
Agreed. I am estimating that once the MAA is approved and provided the Edens
system is fully functional, NWBO/Advent may end up with a clientele of 2000 UK patients
that first year and a profit of about $100,000 per patient. The total profit would therefore
come to about $ 200 million that first year. This estimate is purely based on patients
available in the UK and does not deal with possible earnings in other jurisdictions,
partnerships, etc.
I do not know if that earning estimate is exactly in the ballpark but if it is, those profits
alone could increase the SP to somewhere between 3-5 dollars.
Note: I know that there are currently more than 3200 new cases of GBM in the UK
each year but I doubt that all the UK neuro-oncologists will recommend the
DCVax-L treatment from the get go. I am therefore estimating that about
2000 UK GBM patients (and perhaps some Grade III glioma patients) may be
treated during the first year following the MHRA approval.
Thank you Zadie and what is your guess about a cemented MAA?
Question is: If it is swift, how swift is swift?
Faster denial and faster approval.
Hi again Churchill. I believe that most of the companies
submitting an MAA to the MHRA only PR the submission
but not the acceptance because the MHRA is discouraging
companies from Press releasing the acceptance of their
MAA applications .
Hi Churchill. By this time the MAA submission would have either been
accepted or rejected. Since we have not heard anything by now we can
deduce that it was accepted because if it had been rejected, NWBO would
have had to PR that fact because a rejection would be a material event.
Since NWBO did not PR the acceptance or rejection, I am quite certain
that the application was accepted.
Thank you Perk_Idaho.
What is "FOIR" ?
I believe Doc logic that you may have been right when you wrote
that EDENS may have been a part of the MAA submission to the MHRA.
This is also my guess and is based on LP's statements made on October 13
2023 in which she discussed the delay in the submission. She told us that
after overcoming an unexpected delay, the MAA submission could soon be finalized.
Maybe the unexpected delay was based on the assumption a few months earlier
that the EDEN manufacturing protocol was already up to par and could be included
in the submission but thereafter they found out that it was not yet ready, hence the delay.
Then unexpectedly they overcame that problem during a relatively short time with the
result that the EDEN manufacturing protocol was included in the MAA.
Perhaps LP's quote below emphasizes that it was important to submit a full strength
MAA to the MHRA (including EDEN?) because NWBO planned to submit the
application to multiple regulators. I know that I am speculating but LP may have
meant that it would be okay to send to the MHRA an MAA that only included the
manual method because that is adequate for the UK clientele but it would be especially
important to include EDEN in the submission since that methodology can be easily
utilized to serve the many more patients in other jurisdictions.
[quoteThe Company strongly believes that after so many years of work on the DCVax-L program, taking some additional time to help ensure that the full MAA package is as strong as it can be is especially important since the Company plans to submit applications to multiple regulators. ][/quote]
Newman, I somewhat disagree, My instincts also tell me
that the SP can go down to below 50 cents (maybe not to
40 cents) and that this may last up to late March (shortly
before the CHMP meeting). There may be some good news
in between such as the results of the UCLA combo trial, and/or
news about the lawsuit but the downtrend may still be with us even
until MHRA approval.
Thank you Dstock and especially for the 3 additional links. As the contents
of those publications are very complex, it will take me some time to comprehend
the research. I hope that it will give me an idea as to the possibility that
autologous dendritic cells can be utilized to more effectively combat or
even cure HIV.
As to the shorts and fuddsters on this MB, I believe that we should sometimes
read their posts because they are often so nonsensical that in fact it reinforces the
evidence that DCVax will have a bright future. I would just rarely answer such
posts because the lack of response will marginalize these worthless folks and
that will greatly increase the quality of our MB.
I wish Branster that you will reconsider your decision and give it a try
to stay on this MB and if you have decided to leave, know that I
and probably many longs will be happy to welcome you back.
I agree that this MB has deteriorated a lot. Right now after reading
your post, I have decided to no longer respond to the incessant bashers
that are trying to deviate our attention from the extremely positive trial
results and very promising future of our company. If we limit our posts
to discussing and debating the progress and future direction
of the company while ignoring the detractors, I strongly believe that
this MB will regain its previous top notch quality.
I hope that many other MB longs will join me in this change of direction
that I believe will allow us to maintain the previous super quality of our MB.
As for the shorts, bashers and detractors, let us limit them to talking to each other.
Correction: 40 Inquirig posts since 12:01 am today.
More than 30 Inquirig posts since 12.01 am, Today, That could be a record.
Thank you Dstock for your complement but to be honest, at the time of
my retirement, the sciences of immunology and immunotherapy were still
coming out of the stone age and like so many of us, I have been struggling
to keep up with the rapid pace of development.
One of the articles you just sent me is Jan Kristoff's very interesting 2019
doctoral dissertation which demonstrates that the treatment of HIV
patients with dendritic cells is very difficult. Perhaps a DCVax-L type
treatment which utilizes the HIV virus may or may not work but my
guess is that even if it works, that treatment may have to undergo a lot
of modifications.
The second article you sent me is also interesting in that it shows
that even relatively young patients with HIV who for years were
stabilized and kept alive by the retroviral medication, had an mOS of
only 8 months after they were diagnosed with GBM and that despite
the fact that as a group they also responded well to radiation and chemo.
The fact that currently the mOS of mostly older GBM patients is about
16 months, strongly suggests that the normal immunological defenses
of even older individuals, have the capacity to retard the growth of the
tumors for months after initiation of the cancer. That simply suggests
that the success of DCVax-L (+poly ICLC etc.) depends on strong
inherent immunological defenses. I therefore doubt that DCVax-L will
be able to significantly help immunocompromised HIV patients.
Could HIV's patient's dendritic cells cultured together in vitro with an adequate
concentration of HIV be immunologically stimulated enough when injected
back into the patient, to initiate an effective anti HIV immunological response
that would lead to a cure?
In the case of the HIV patient, perhaps the stimulated dendritic cells can destroy
the HIV virus in the initial stages of the disease before the cell mediated immune cells
(e.g. T cells) are destroyed by the HIV infection. However, I doubt that once most T cells are
destroyed by the virus, any number of even very potent stimulated dendritic cells can be effective.
My guess: HIV stimulated dendritic cells may help recently infected HIV patients but not
advanced cases of HIV whose natural cell mediated responses have been debilitated.
If my guess has legs, it may be worthwhile for the industry to help the early cases of HIV
and make some money while doing it.
Very interesting Dstock. I wonder what proportion of the ads that Merck
submitted a few years back, contained so many references to the
manufacture of vaccines. At least it may give us an idea of the
magnitude of Merck's change of focus regarding their manufacturing
and marketing objectives.
I would guess that along with the dynamic increase in Merck's construction
of manufacturing facilities coupled with at least a 200-300% increase of their
vaccine mentioning ads, the chances are very good that DCVax manufacturing
is in Merck's mix.
I am guessing Inquirig that you are spending so much time on this
MB, that you have no time left for anything else BESIDES.....
Thank you Inquirig for your ever increasing number of anti NWBO posts
that most likely reflect the ever increasing panic of your employer(s).
Very much hoping Doc that you are right. I am really looking forward
to a number of very favorable developments during the coming
months (by the end of Q2?).
Georgebailey, According to ATL, the MAA included all grade 3 and 4 malignant glioma
cases. I believe that the UK has already surpassed 3000 new cases of GBM (grade 4) annually.
Last I heard was that Sawston had the monthly capacity to produce DCVax-L for about
40-50 patients. Hopefully this capacity has increased. However, I question whether
it has increased so as to cover over 2000 patients annually.
I am therefore wondering whether the MAA contained a provision for using the EDEN
automatic manufacturing methodology and whether the pertinent validation request has accompanied
the MAA or this request had already been submitted and approved prior to submission of the MAA.
Flipper, approval followed only by increasing vaccine sale revenues few months to a
year post approval is my worse case scenario. However, in this scenario, even a relatively
subdued SP will be outmatched by an ever increasing stream of revenues that will demonstrate
the company's fiscal strength. Therefore, it won't be long thereafter that a deal with one of the BPs
(Merck?) could be struck.
In reality I don't believe that we will have to wait months or a year post MHRA approval
but rather that a successful deal could be cemented days or weeks after approval.
Great work ATL. I wonder whether the Advent's current manufacturing
method may already include the validated automatic manufacturing (EDEN)
because I believe that there are more than 3000 new cases of grade III+!V
malignant gliomas in the UK each year.
I know that not all of the physicians of the very new patients will recommend the DCVax-L,
treatment but within a short period of time, most of them will. I doubt that the manual
manufacturing method will be able to cope with the demand and I am wondering
whether the MAA perhaps includes the provision that EDEN's efficacy has already been
established.
Given the increased demand for the vaccine, it is hard for me to visualize that the MHRA
will extend its approval to an MAA that is dependent on the manual manufacturing process.
If Keytruda's falling of the patent cliff could be remedied for example
by treating patients with viral vaccines whose potency has been shown
to be greatly increased by a co-administration of keytruda, a large
financial investment by Merck to manufacture those modified vaccines would
seem extremely logical. If someone is aware of that potentially successful
vaccine combo, please let us know.
OTOH at this point, there probably is convincing evidence that keytruda potentiates
the activity of DCVax-L. We cannot know how much of Merck's present expansion
efforts and finances would be dedicated to develop the marketing of this combo vaccine
but it is one tangible possibility that makes sense whereas completely dismissing
this possibility does not IMHO.
Thanks Dstock for the information concerning the construction periods
of the recently 4 new Merck buildings.
I am becoming ever more convinced when I see those Merck job Ads
include the word "vaccine" as part of Merck's production goals and all
I would now ask Merck to do is to include the word "autologous" in front
of every vaccine word. That may finally even convince the bashers on this MB.
Thank you Dstock for providing the information that by the time
that Merck was involved in the combo trial, they had plenty of
information to collaborate with NWBO. By the time the combo
trial was initiated, the increased efficacy due to the addition of
poly ICLC should have been obvious and the addition of keytruda would
not seem so daunting especially if much data was also already available
from the UK Specials and Expanded Access Programs.
I do believe that within the next 6 months we will get more information
about Merck's collaboration with NWBO. I am also not excluding the
possible involvement of other actors but if true, we will get that information
as well.
Dstock, While you have presented a lot of interesting evidence that Merck has
been working quietly with NWBO on developing the DCVax-L treatment,
I am quite surprised that Merck's 3 applications for the construction of new
manufacturing facilities (that you just posted) were submitted already throughout
2021. In fact, the application to add manufacturing and office space for vaccines
was dated 2/2/21, barely 4 months after data lock.
Now it is possible that alredy by early 2021 Merck was convinced that DCVax was very efficacious
and Kevin Duffy's work with NWBO may have been one of the catalysts. It is just that the first
positive DCVx-L results were publicized on 5/10/22, 15 months after Merck's application
to add manufacturing and office space for vaccines. For Merck to make such a financial
commitment at that time, they must have already been convinced that DCVax is the golden goose.
This is not impossible if Merck had already some decisively positive information about the main trial
(data beyond the 2018 JTM publication) as well as some preliminary, very positive results from the
combo trials.
Thank you Doc. Since to date all the preliminary results of several small trials
have indicated that the combo treatment (DCVx-L+poly-ICLC) tends
to be safe and increases the already positive effect of the monotherapy
(DCVax-L ), is it safe to say that on approval of DCVax-L by the MHRA,
the physicians will most likely recommend that their patients in lieu of the
mono therapy, receive the combo therapy poly(DCVax-L+Poly ICLC)?
If that is the case, as time goes on and more trial results accumulate, CIs (e.g. keytruda)
and/or other adjuvants that have demonstrated safety and increased efficacy will join the
combo therapy.
Gary, I believe that Poly-ICLC is a maturation agent for DCVax (L and D) and therefore
should be as effective for other cancers as it is for GBM. OTOH, I am guessing that
the efficacy of DCVax itself may vary from one type of cancer to another and that may depend
on the extent, makeup and locations of the mutated cancerous antigenic moieties.
As for NWBO swallowing of Oncovir, I am all for it if the price tag is reasonable.
Here is my take on the MAA's acceptance/rejection in the order of
decreasing probabilities.
1. Most likely the MAA was already accepted but the company decided not to PR.
2. Due to the holidays and the length of the MAA the, MHRA has not yet
completed its review but will do so very shortly.
3. NWBO had to make a few revisions or correct a few errors, followed by a
resubmission and a final review of the MAA by the MHRA.
4. The MAA was or is about to be rejected by the MHRA and NWBO will inform us
of this via a PR.
Hope you are right Flipper on the SWIFT program and NWBO's MAA being
a pioneer beneficiary. Come to think of it, if I m not mistaken, some time ago
Dr. Ashkan mentioned that once the MAA is filed, it would only take a couple of
months for that MAA to receive MHRA approval.
If Dr. Ashkan indeed expressed that opinion, was it based on hope or exuberance
or on solid information?
Thank you Hankmanhub and Gary for your input.
While the many pages in this submission may have greatly delayed
the entire process of MAA submission, LP's statements suggest that
this did not affect the particular delay she was referring to because it was
in her words an unexpected delay that was apparently resolved and by
doing so, gave the company and consultants the opportunity to upgrade
the entire application. Apparently this improvement was important especially
because the MAA was to be submitted not only to the MHRA but to
other regulators as well.
With respect to an MAA with the manual vaccine production, I agree with Gary that it
would be adequate for the UK and perhaps with time also adequate for the USA but
an MAA that includes a validation of EDEN, would be of much greater value IMHO.
However, let us assume that the upgraded MAA did not include the validation of the
EDEN automatic manufacturing system and will include only the validation of the manual
production. Now what was the reason that the post delay MAA was such an improvement?
Answer: we still don't know and as of now, I have not received any suggestions that seem
more credible than my suggestion.
"The Company and its consultants are working intensively to finalize this last key section of the MAA, after overcoming an unexpected delay in that regard. The Company strongly believes that after so many years of work on the DCVax-L program, taking some additional time to help ensure that the full MAA package is as strong as it can be is especially important since the Company plans to submit applications to multiple regulators."