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Because the vast majority of crossovers are composed of mesenchymal GBM while treatment arm consists of much much less mesenchymal GBM.
If you are interested, you should compare OS of mesenchymal GBMs between the crossovers and the treatment.
Contrary to SOC or other treatments where mesenchymal GBMs are the worst group in terms of OS, in our DCVax-L trial, patients with mesenchymal GBMs have experienced the best OS outcomes, regardless the arms.
Thank you eagle8. That's my understanding in a strategic level. In terms of tactical level, I do think contrary to the mood of the board or the sign shown from reading the share price movement since after 10 May presentation (short attack), we are actually golden if one holds, or more than golden if one continually adds shares at this price range:
The bear are mostly opportunists who have taken advantage of no imminent breaking news since the company is observing a quiet period, either because of journal embargo or more realistically regulatory negotiation. But, they have been highly in debt of shares, indicated by unprecedentedly high volumes of shares deemed fail to deliver, and this part is only a tip in the iceberg if naked shorts are considered.
And news although most may think it's not imminent, who knows when?
The long have been endured hardship and now have been seasoned. Faced with the same situation of vacuum of news/update/next steps, etc., we are holding our shares at close to years' low end, meaning the bear have equivalently loaded with either borrowed shares or naked shorted shares in an unprecedented level.
Despite short-term doom injected by defenselessness quietness, the long-term prospect is bright, even the short know DCVax-L will get some kind of regulatory approval, if not a widespread approval and newly adopted standard of care most long and average persons believe after digesting the great trial data released at NYAS on 10 May that both the primary and secondary endpoints are met statistically significantly.
So who should have a good sleep? Are those who have been heavily in debt of shares or those who have held and continually add shares?
Like FED has been forced its hand to resort to hawkish stand to raise interest rates, MMs will be in a short while forced to buy back shares, let alone the usual naked shorted wolfpack who are doomed.
If you add shares today, you are not brave, you are smart!
GL
To the board: Think a bit more rationally out of box. We are much more than whether or when a publication of trial results will come or in which prestigious journal will the results be published, because that's not the point.
Making no mistake, the results will be published in a first-tier medical journal. If you have not realized this, you cannot be taught!
There is definitely something more than just a publication, and of course it's the approval of RAs, particularly FDA. To that end, Linda has put the whole management team into an endless quiet period, and when things are settled, it may show it's an indeed a wise decision for all parties involved.
So "forget" publication because it's a convenient and strategic thing up to this point.
So it's absolutely possible a RA approval may come earlier than the publication, or come simultaneously or a short time spaced.
The most important thing which the company has pursued so far is regulatory whisper.
$NWBO $XBI @POTUS
— Arh Dan (@Arhdan9) June 7, 2022
Refreshed FDA whispers: here you go #NWBO #GBM #immunotherapy #endcancer #moonshot #innovation #reincarnation #humanity. Boom you go $NWBO - my humble understanding of the current and near future status. Ignore negativity! All will come into place in due time! pic.twitter.com/SHUxPpTQFZ
Instead of useless debates and dispositions, save your time and others reading the following and then think hard (never stressed enough unfortunately).
Benefit-Risk Assessment in Drug Regulatory Decision-Making
Benefit-risk assessment is the foundation for FDA's regulatory review of human drugs and biologics.4 In. PDUFA V, FDA's Center for Drug ..
https://www.fda.gov/files/about%20fda/published/Benefit-Risk-Assessment-in-Drug-Regulatory-Decision-Making.pdf
When it comes to FDA approval, the simple question is "does the drug/biologic product's benefits outweigh its risks?" Please applies this to NWBO DCVax-L approval for #GBM.
Although not approved yet, the headline today re Novavax Vaccine expert opinion should fill the emptiness caused by doubts and uncertainty re NWBO.
FDA Advisors Say Novavax Vaccine’s Benefits Outweigh Its Risks, Clearing Way for Authorization
Last Updated: June 7, 2022 at 3:46 p.m. ET
First Published: June 7, 2022 at 8:01 a.m. ET
Does the benefits of DCVax-L for GBM outweigh the risks?
It's exciting news but first you have to put thing in perspective: for this kind of cancer (localized, not yet spread) 5-year survival rate is more than 90%, and the trial has now only followed these small number of patients up to 25 months.
It's still a long road to go to see if the exciting results today can hold.
But good for them, congrats!
[Compare that to the prognosis of GBM, you know the story. Cheer]
AF and the statnews are about nothing they have ever claimed to be as journalist and a premier health news outlet, but all about finding the niche to profit, which is cheer leading for big pharmaceutical companies while on the same purpose bashing and destroying small biotech companies which are a threat to big Ps, so that the big Ps can either operate their business as usual or scoop the innovative small biotech companies pennies on the dollar.
So really nothing about the truth, or the whole picture, the common sense, but all about footing for their bosses, the big Ps, in anyway allowed or not allowed by the law.
This is not a structure with written specifications or binding documents, but their modus operandi.
So really only thing can withhold them is conscience. In the case of AF, nothing can withhold him, for he has no conscience at all.
Again unbelievably naive opinion/observation from a pro. Ever heard the term Naked Shorting?
If the debate whether there is naked shorting whatever in the Great United States of America stock market, or in particularly has there been significant naked shorting ongoing against the tiny biotech nwbo may have some warrant after the maddening downfall of price from +$12 to mere $0.14 on suspected false trial fail narrative and before 10 May 2022, the eventful day when the suspected naked shorting footing AF again was "re-glorified" with the participation of all MMs that anyone can easily name them, with price dropped a whopping 78% on that single day alone on the backdrop of in effect the presentation of very good trial results at NYSA.
Not a single or several and in effect any funds/persons would buy a stock like a drunken sailor and then sold all in a single day as if the earth would no longer exist tomorrow. None, if not for one purpose and the only purpose which is to drive the company to bankrupt or practically for our case today to force the company to become a bottom fishing stock for acquirer(s).
Sound depressed, yes if you are a swing trader, but no one is a long-term holder. The evil force will let it go. They have no choice. Data is out, Not everyone is dumb enough to understand what these data sets as whole mean in terms of RA approval.
That eventful day and the trading after that day indicate the naked short wolfpack is indeed alive and well in our land, they will serve us well when time is come.
Those MMs actually are very funny. You cannot get the shares you want when there are no shares available. It's better to get it below $2 instead much higher.
Those money making machine (algo) will learn one thing or two soon.
Implication? Safety, safety and safety!
cart-t which Statnews has been pumping is dangerous while DCVax-l, autologous dendritic cells pulsed with tumour lysate antigen is very safe as shown by data presented at NYAS on 10 May.
Next and the last check is whether it is also efficacious and the answer is also yes. So it's unfathomable why FDA will not approve on its own ground of benefit-risk assessment.
The market is now in a shitty situation. Most development stage biotech companies have been traded below their cash value. In this sense, we are relatively faring well.
Thing may change if ......
yea it's the low expectation and the fact that Linda and the gang have so far failed to actively and positively engage the market that may in effect this time get into it after they climb out of the embargo hole.
I don't hold my breath either, but even a tortoise will eventually get there.
Arh Dan
@Arhdan9·
2h
$NWBO $XBI @ASCO
#ASCO
Still a bit doubt w/ the primary endpoint OS for nGBM met w/ p-value <0.002, then the doubt will be cast aside that the secondary endpoint OS for rGBM also met w/ even more significant separation & p-value <0.001. RAs will approve DCVax on their own ground:
https://twitter.com/Arhdan9/with_replies
Not necessarily. SP can change drastically and the uptrend can sustain if
1) one or two major funds take significant position, something around 1% of the float, and because of their sizes, willing to absorb any short selling, naked or not, thereby at least maintain the steadiness of sp. After that the market will take care of it for continued appreciation uptrend, and/or
2) Any definite sign of RA approval. We long-term investors or investors who have done enough DD all know UK is in that position to approve, but the market doesn't know which is waiting for a definite sign, like a pr, and/or
3) Any definite sign/pr indicates FDA is onboard with SAP, endpoints, or the company can reveal some positive discussion with FDA re BLA application with positive comments, and/or
4) A huge push-back the notion that the trial data is not adequate for FDA approval by advocacy groups which are already happening, oncologists, regulatory experts, especially after publication.
5) Miraculously, the naked short cabal is disbanded, or their footing AF is indicted with manipulation via distorted reporting, misinformation, etc.
As I hate to say, but yes it could be any day or days for a major shift and dynamic sea change.
TAs are useless shits in high alpha and beta biotech companies particularly NWBO. Now with preliminary data out to the public (NYAS presentation), only thing that matters in terms of stock price/trend is where are the buyers and where are the sellers.
This is a battle between light and darkness. Linda and the gang should now have had the upper hand with both primary and secondary endpoints being met statistically significantly, and the expectation of more encouraging data when the publication comes out.
It's really a puzzle with such beautiful data that Linda, Les, Dave have so far failed to locate and secure a significant somebody who has the resources to get in big, withstand and thwart any future naked short shitty actions. Have expressed my displeasure to the company but they seem as if they didn't know how to do it!
Linda, Les, and Dave should all be focused on this one single most important thing. Get out the comfort zone and get somebody big onboard.
Forget the BiggerC, or island boy clubs or the like. they are either too convenience-oriented or small to do something really meaningful.
So I am patiently waiting, even Linda, Les and Dave continually fail in this endeavor, I believe somebody big will find us, and the light will shine while darkness will fade away!
AF knew endpoints of DCVax-L trial had been changed from PFS to OS long before his distorted misleading article, in both the US and EU. He has had absolutely no basis for his distorted 10 May article.
The presentation is full of data, nobody would pick just a historical part (PFS data) and ignore the vast majority of data.
The objective view/analysis should look at whether the data shows DCVax-L is working or is efficacious from all data presented as a whole.
So AF is as usual a disgusting hitman.
On today's smithonstocks article: generally an insightful and plausible rebuttal to AF's said scandalous, distorted, misled article.
Although smith wrongly cited clinicaltrial.gov as source for OS primary and secondary endpoint at the time, Smith's point is still intact because AF had for several occasions openly acknowledged and attacked that Northwest Bio has updated the trial endpoints in both eu and us via tweets well before 10 May 2022 when his said article was published.
As Smith suggests it may be much useful to write to AF's superiors to demand retraction of the misleading article, fire AF, and apologize, which I agree and have done so, than just hang on in this board "complaining or pumping."
We are 35,000 investors strong, if we are united even by 10%, we can do a lot of wonderful things!
Much more optimistic than that IMHO. From the NYAS presentation it's strongly suggested if more vaccine doses can be made initially than the usual three-year of usage made and used in the trial, and if new vaccines can also be made from recurrent tumors when patients metastasize, then the overall survival of the same patient population will be much longer than those reported.
So in practice, the chance of patients living longer than those reported is much higher if more vaccine dosages are made, and new vaccines are made from recurrent tumors.
Besides, the most important thing for RAs to approve DCVax-L is much more than making available of a new treatment for nGBM and/or rGBM patients, but making available an essential agent (DCVax-L) in various combination trials such as those with Keytruda for potential cures for cancers.
Potential wise, if the approval of DCVax-L for nGBM and/or rGBM is 1, then approval of DCVax-L for other cancer indications will be 10, and the combination if successful will be 100.
This is real and meaningful work done by a real long. It's useless to clutter the message board/social media with endless discussion/debate on basically nothing, perhaps for "self-satisfaction," or hoped a few pennies swings.
What's you have done recently is very meaningful, thank you very much AEK.
For those of you who have argued there has been no significant short force working together in attempt to destroy NWBO share price, or those who don't believe there is a naked short cabal who have been trying desperately to destroy this company, thereby its DCVax-L vaccine product, please shut up once for all!
Life has ups and downs. Longs are on the right side in this fight. Together we will win the battle and win bigger, much bigger than usual because of the short cabal.
Our will has never been this stronger while the short's is about to collapse.
I have explained this in one of my previous post: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=168865226.
Background: the control [edit: treatment] consists of 232 nGBM patients; the control consists of 99 nGBM patients initially, and then 64 patients of the 99 patients who crossed over to receive DCVax-L treatment plus 35 patients who have never been treated with DCVax-L.
It's known that about 30–49% of GBM tissues have been classified as the mesenchymal subtype. Patients with this subtype, both with primary and recurrent tumours, tend to have the worst survival rates compared to other subtypes (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485274/). [Before DCVax-L emerges as the most effective treatment for this group, see below]
The beauty with DCVax-L in treating this subtype of patients is that as Dr. Liau has persistently pointed out over the years, despite the worst prognostication of this type treated with any other treatments available before DCVax-L, it has shown stellar efficacy when treated with DCVax-L [this conclusion can trace back to when Dr. Liau conducted Phase1/2 DCVax-L trial for nGBM more than a decade ago].
Patients from the control (n 64+35) at/after the recurrence those 64 patients have significant higher percentage of the mesenchymal subtype than that of the treatment arm (n 232).
I agree and thank you for your contribution. In addition, based on incompetent management, the price will go higher, much higher, suggesting much of the price crash is due to the management. So when the truth is told in the market, share price should have more powerful tailwind to carry it higher.
This is my last post allowed for today, so GLTY, and GLTA!
Despite what you said may be true, but don't underestimate them, and us retail investors! I mean, come on, the trial data is out there for anyone to analyze.
Before they might have done what you suggested, that is because there was no unblinded data; now things would change with unblinded data known.
De-risk should become a catch word for all investors and potential investors!
Big shareholders where are you? I have no rights to tell you what you should do on day like today when price crashes for a despicable untrue reason -- "failed" PFS? Sloppy journalism, mismanaged company, and you name it.
But I do know what I should do. I own much less shares but still managed to buy on day like this. Today not many, rounded up about 30K, but on 10 May I bought two batches of about 100K each.
We are not crazy and we have FDA approvable paradigm-shift immunotherapeutic cancer vaccine on hand indicated by unbiased analysis of already known data (NYAS presentation on 10 May).
The short are weak despite having succeeded in "making the significant down market" with merely a million or so of shares in disposal in day like today as trigger, the rest comes from panic selling, sheep following, etc.
So if we are united, and do what we can afford to do, we will be able to protect our shares while finally dissolve any possible vicious attack like today or days ahead by the short.
If you like this rhetoric yet truth within commentary, let it known to all investors. Thanks.
It seems the short have raised some seemingly savvy analytical observation that the control arm outperforms treatment. This has confused a lot of investors or would be investor, but what on earth is the truth?
Before tipping the toe into it in more detail, let us all remember the overall picture: DCVax-L is indeed working statistically significantly for both nGBM and rGBM. In overall, the data shows:
NEWLY DIAGNOSED GBM:
mOS: 19.3 mos from randomization (22.4 mos from surgery)
vs. 16.5 mos from randomization in controls
mMGMT mOS: 30.2 mos from randomization (33 mos from surgery)
vs 21.3 mos from randomization in controls
Survival Tail: 13% vs 5.7% at 5 years
RECURRENT GBM: mOS: 13.2 mos vs. 7.8 mos from recurrence
Survival Tail: 20.7% vs. 9.6% at 24 mos after recurrence
11.1% vs. 5.1% at 30 mos after recurrence
Now some context: is unblinded data in aggregate as of October 2020 less stellar than the blended data in 2018?
First, we have not seen unblinded data in aggregate yet (not contained in May 10 NYAC presentation), but by just looking at the seemly innocent data, it does seem the treatment arm underperform the data in 2018. The reason is in part because the last batch or the last batches of patients are sicker than the previous' as it's suggested from Germany where the last patients sicker (lower KPS rating at the baseline visit for example) were enrolled. As a result, if the blended patients in 2018 have a five year survival of 28%, the five year survival at the unblinding in October 2020 would be most likely less than 28%. So it's not apple to apple if comparisons are made, and this is possibly a factor which reveals the short's argument dishonest.
Then, most importantly, does the control arm outperform the treatment arm? From the incomplete data presented at NYAC, on surface the answer: probably, but after analyzing a bit more in depth, then answer is a resounding no.
Background: the control consists of 232 nGBM patients; the control consists of 99 nGBM patients initially, and then 64 patients who crossed over to receive DCVax-L treatment plus 35 patients who have never been treated with DCVax-L.
Okay please bear with me: it's known that about 30–49% of GBM tissues have been classified as the mesenchymal subtype. Patients with this subtype, both with primary and recurrent tumours, tend to have the worst survival rates compared to other subtypes (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485274/). [Before DCVax-L emerges as the most effective treatment for this group, see below]
The beauty with DCVax-L in treating this subtype of patients is that as Dr. Liau has persistently pointed out over the years, despite the worst prognostication of this type treated with any other treatments available before DCVax-L, it has shown stellar efficacy when treated with DCVax-L [this conclusion can trace back to when Dr. Liau conducted Phase1/2 DCVax-L trial for nGBM more than a decade ago].
So excluding other possible but less impact factors and putting everything in equal, it seems the mesenchymal subtype is the deciding factor in solving many puzzles arise by the short, including the confusing puzzle: does the control arm outperform the treatment arm?
So depending on the percentage of the mesenchymal patients in each arm, it would be easy to understand/predict the outcomes of these patients post DCVax-L treatment.
So because the 232-patient treatment arm are randomized nGBM, the percentage of its mesenchymal patients, though similar or equal to that of its comparator ECT arm, would be significantly lower than the control arm which consisting mostly the 64 cross-over patients as the patients would shift towards mesenchymal subtype upon glioma reccurrence. See below quotes within the quotation marks:
"The shift towards mesenchymal subtype upon glioma recurrence [from the same source cited above]
Interestingly, the mesenchymal subtype at tumour recurrence tended to have a worse overall survival (Wang et al., 2016). However, the frequency of mesenchymal and proneural subtypes was highest among recurrent tumours, confirming previous findings about classical being more sensitive to treatment (Wang et al., 2017b)."
So in effect, it is not the control arm which probably outperforms the treatment arm, and as a matter of effect it's because the control arm consists mostly cross-over patients with overwhelming mesenchymal subtype patients while the treatment arm is composed of much less percentage of the mesenchymal subtype patients.
If given the same percentage of the mesenchymal patients in the treatment arm as equal to that of the control arm, it would not be difficult to see the treatment arm will significantly outperform the control arm.
At this point, a new question may arise: so wouldn't it be better for all the patients to wait until progressions for DCVax-L treatment, because in this way most patients may transit to the mesenchymal subtype which would be most favorable for DCVax-L treatment?
Well, first of all, there are patients in the treatment which are already of mesenchymal subtype, so these patients should be treated with DCVax-L ASAP; second, not because DCVax-L may be most effective in treating the mesenchymal subtype, doesn't mean it is not working with other subtypes, so all the patients should be treated with DCVax-L immediately after surgery and radiochemotherapy.
In the future, all the nGBM patients treated with DCVax-L made from the initial tumors should continue with the treatment with newly made DCVax-L from the recurrent tumors. Obviously, in this way, the overall survival of these patients will be most likely increased substantially further again.
Hope this will be helpful in debunking the short's argument, and this message/opinion is not detail, complete or comprehensive enough which will take a much longer time to write; it's however may serve as a clue for those interested to start digging further.
I also believe the publication when comes out will answer many questions or much of the confusion we may currently be having, and there will be more efficacy evidences from the publication.
Lastly, this fiasco or confusion may not be as prevalent as what we have seen today, if most investors understand why the halt:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145658266
I will be absent for a few hours from now so sorry there will be no response from me; also sorry for this rash-in commentary without much editing.
It seems the short have raised some seemingly savvy analytical observation that the control arm outperforms treatment. This has confused a lot of investors or would be investor, but what on earth is the truth?
Before tipping the toe into it in more detail, let us all remember the overall picture: DCVax-L is indeed working statistically significantly for both nGBM and rGBM. In overall, the data shows:
NEWLY DIAGNOSED GBM:
mOS: 19.3 mos from randomization (22.4 mos from surgery)
vs. 16.5 mos from randomization in controls
mMGMT mOS: 30.2 mos from randomization (33 mos from surgery)
vs 21.3 mos from randomization in controls
Survival Tail: 13% vs 5.7% at 5 years
RECURRENT GBM: mOS: 13.2 mos vs. 7.8 mos from recurrence
Survival Tail: 20.7% vs. 9.6% at 24 mos after recurrence
11.1% vs. 5.1% at 30 mos after recurrence
Now some context: is unblinded data in aggregate as of October 2020 less stellar than the blended data in 2018?
First, we have not seen unblinded data in aggregate yet (not contained in May 10 NYAC presentation), but by just looking at the seemly innocent data, it does seem the treatment arm underperform the data in 2018. The reason is in part because the last batch or the last batches of patients are sicker than the previous' as it's suggested from Germany where the last patients sicker (lower KPS rating at the baseline visit for example) were enrolled. As a result, if the blended patients in 2018 have a five year survival of 28%, the five year survival at the unblinding in October 2020 would be most likely less than 28%. So it's not apple to apple if comparisons are made, and this is possibly a factor which reveals the short's argument dishonest.
Then, most importantly, does the control arm outperform the treatment arm? From the incomplete data presented at NYAC, on surface the answer: probably, but after analyzing a bit more in depth, then answer is a resounding no.
Background: the control consists of 232 nGBM patients; the control consists of 99 nGBM patients initially, and then 64 patients who crossed over to receive DCVax-L treatment plus 35 patients who have never been treated with DCVax-L.
Okay please bear with me: it's known that about 30–49% of GBM tissues have been classified as the mesenchymal subtype. Patients with this subtype, both with primary and recurrent tumours, tend to have the worst survival rates compared to other subtypes (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485274/). [Before DCVax-L emerges as the most effective treatment for this group, see below]
The beauty with DCVax-L in treating this subtype of patients is that as Dr. Liau has persistently pointed out over the years, despite the worst prognostication of this type treated with any other treatments available before DCVax-L, it has shown stellar efficacy when treated with DCVax-L [this conclusion can trace back to when Dr. Liau conducted Phase1/2 DCVax-L trial for nGBM more than a decade ago].
So excluding other possible but less impact factors and putting everything in equal, it seems the mesenchymal subtype is the deciding factor in solving many puzzles arise by the short, including the confusing puzzle: does the control arm outperform the treatment arm?
So depending on the percentage of the mesenchymal patients in each arm, it would be easy to understand/predict the outcomes of these patients post DCVax-L treatment.
So because the 232-patient treatment arm are randomized nGBM, the percentage of its mesenchymal patients, though similar or equal to that of its comparator ECT arm, would be significantly lower than the control arm which consisting mostly the 64 cross-over patients as the patients would shift towards mesenchymal subtype upon glioma reccurrence. See below quotes within the quotation marks:
"The shift towards mesenchymal subtype upon glioma recurrence [from the same source cited above]
Interestingly, the mesenchymal subtype at tumour recurrence tended to have a worse overall survival (Wang et al., 2016). However, the frequency of mesenchymal and proneural subtypes was highest among recurrent tumours, confirming previous findings about classical being more sensitive to treatment (Wang et al., 2017b)."
So in effect, it is not the control arm which probably outperforms the treatment arm, and as a matter of effect it's because the control arm consists mostly cross-over patients with overwhelming mesenchymal subtype patients while the treatment arm is composed of much less percentage of the mesenchymal subtype patients.
If given the same percentage of the mesenchymal patients in the treatment arm as equal to that of the control arm, it would not be difficult to see the treatment arm will significantly outperform the control arm.
At this point, a new question may arise: so wouldn't it be better for all the patients to wait until progressions for DCVax-L treatment, because in this way most patients may transit to the mesenchymal subtype which would be most favorable for DCVax-L treatment?
Well, first of all, there are patients in the treatment which are already of mesenchymal subtype, so these patients should be treated with DCVax-L ASAP; second, not because DCVax-L may be most effective in treating the mesenchymal subtype, doesn't mean it is not working with other subtypes, so all the patients should be treated with DCVax-L immediately after surgery and radiochemotherapy.
In the future, all the nGBM patients treated with DCVax-L made from the initial tumors should continue with the treatment with newly made DCVax-L from the recurrent tumors. Obviously, in this way, the overall survival of these patients will be most likely increased substantially further again.
Hope this will be helpful in debunking the short's argument, and this message/opinion is not detail, complete or comprehensive enough which will take a much longer time to write; it's however may serve as a clue for those interested to start digging further.
I also believe the publication when comes out will answer many questions or much of the confusion we may currently be having, and there will be more efficacy evidences from the publication.
Lastly, this fiasco or confusion may not be as prevalent as what we have seen today, if most investors understand why the halt:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145658266
I will be absent for a few hours from now so sorry there will be no response from me; also sorry for this rash-in commentary without much editing.
To be conservative, the fund raised in the the month following the 1st Q should be around $10 million, assuming average strike price of around $0.25.
Nonetheless, the gist of my previous post is the same.
Happy days ahead.
GL
So we have enough money as of now --- well over 20 millions raised in the past few day.
So those vulture funds who may participate in the recent crash, eagle to have their name including in an "imminent" financing post data are disappointed!
No worry about imminent dilution. Price will once again head north all the way to approval.
Let us move on ladies and gentlemen, be focused on more important things, like publication, ASCO presentation, combination trial revealing/results, partnerships, regulatory filing announcement, buyout interests, ...
Thanks for dropping in giving your assessment, I was looking for your comments actually after the presentation on this board. Before heading out to take a long walk along the river, I would like to add re efficacy:
Besides the statistically significant p-values and clear separations between the curves in general, the no.1 clue for me is the "failed" PFS due to pseudo-progression, which in and by itself coherently is a undeniable sign of efficacy;
Similarly, no.2 is the beautiful, clear separation of curves with beautiful p-value with regard to rGBM, another clear and undeniable signal of efficacy.
I guess more overwhelming efficacy signals will come when the publication comes out, including (my guess) statistically significant secondary endpoint cPFS, and the last secondary endpoint of tumor response, which I believe will also give substantial evidence DCVax-L is indeed effective.
Have a good weekend all!
Sharp rise of price by a buck in one or two days is a real possibility as the market digests the information contained in the NYAS presentation regarding outlined DCVax-L Phase 3 trial results.
The reason is that the market though corrupted infested with the naked short cabal will have a collective intelligence higher than the hitman AF's.
It's a high probability the naked short cabal who caused this crash will be overwhelmed by true Wall Street investors.
I know, I know we are trading in OTC; most of funds are prohibited to buy; there is also $5 hurdle, etc, etc,
But in my book and experience of this world, tailwind can always find way to blow!
Used up my quota of three posts a day.
GL
After carefully reviewing the data known from the presentation, I am becoming more confident DCVax-L will get approved for both nGBM and rGBM by all RAs concerned, simply because the data has demonstrated efficaciousness plus the pristine safety profile of the treatment, and manufacturing readiness.
Going into this presentation, my confidence level was about 65%, today 80%. I also believe and it is logic the imminent publication will have some more compelling evidences of efficaciousness than what presentation contains. So I believe my confident level will increase accordingly.
Any investors should remember this disease is one of the toughest if not the toughest to conquer. Over the past decades, drugs giving a mere 1.5-2 months of OS benefit with much more severe side effects had got approved.
The essential and promising role of DCVax-L which it will play in ultimately conquering the cancers via combination with other approved drugs/agents will be also a factor in consideration of approval.
So at this level of price, I am definitely a buyer. Accumulation of shares takes some time before it's too late to get in cheap. Any day forward is our day I believe.
Thinking about those tens of millions of shares sold in the previous days in prices from $1.9 range all the way down to $0.3. Those shares alone will be bought to cover for the short, repurchased by those sold in panic, ... as data is being digested, let alone the market awareness after the presentation which will draw in new investors.
BTW, for those asking the question, Hodag is a poster over iVilliage who is always wearing a pair of glasses on anything concerning nwbo. He is a little more subtle than most plain bears over their or in this board but always tries to find fault, existing or not regarding nwbo.
My conversation this morning with Hodag regarding a post of JerryC this morning on iVillage:
Jerryc:
presentation slides?
See page 19 labeled "External Controls for nGBM"
I have a ton of experience in stats, but not medical stats, so I'd welcome other voices.
There are 5 comparator trials. There are a number of gaps in data, so a few items are clearly meaningless. Both IDH-1 and Res. Disease only have data from one other paper, so let's ignore those.
KPS score has data from 4 of 5 papers. nwbo's trial is 5% higher than the comparators. You would expect the nwbo patients to do better.
MGMT methylation data is present for all 5 comparators, with an average of 32%. nwbo data is 39%. Again, favorable for the nwbo population.
Tumor resection data is present for 4 of the 5 comparators. The 3 earlier trials are in the range of 54% to 59% complete resection. The one small recent paper shows 74%. Seems like a trend in improved surgical techniques, which correlates with favorable outcomes. Overall, the comparator group has 57% total resection versus 63% for nwbo.
All three of these data points are tilted in nwbo's favor, so this is far from apples to apples.
If this leaps out at me as a stats-competent non-medical person, I assume that any regulator would want to see an analysis to see how much is explained by those factors alone.
Hodag:
Jerry, you can't look at raw numbers and draw a conclusion. You need to look at the averages plus and minus their error ranges to see if they overlap. This is done for you on slide 31 where it shows the hazard ratios. Hazard ratios show the relative risk of being treated with Drug A or Drug B.
The way to read this chart is that if the length of the horizontal line overlaps the vertical dashed line (where the ratio is 1), then the measured benefit is within the range of likely error and, given the way the comparator group was cobbled together, if the horizontal line even comes close to the vertical, that factor will probably not be significant either. 5 of 6 measures cross or come very close to the vertical line, which means that those 5 measures have approximately the same risk between DCVax and the comparator group.
So, what are those results? Two factors (minimal residual disease and MGMT unmethylated) clearly intersect the vertical, meaning that the result is not significant with a 95% CI. Three more lines (Age >65, Age < 65, and MGMT methylated) are essentially intersecting the vertical with values of 0.99, 0.98, and 1.00, respectively). Those would be a hard sell to FDA in an approval setting absent a confirmatory trial.
The final factor, significant residual disease, shows a benefit for DCVax (midpoint estimate 0.65 with a range of 0.48-0.87, that is clearly different from 1.00). That benefit could be due to the immunomodulation provided by the vaccine, a better surgical debulking of the tumor, or a combination of the two.
In the final analysis, does DCVax provide an incremental benefit over the comparator group? Probably it does, but the benefit is marginal. Do these results present a case for having the drug approved as is? Probably not. Can this drug still be approved following a confirmatory trial or a combination trial? Plausibly yes, but that extends the approval date by at least 3-4 years and requires additional clinical work.
Note that while these results are not enough for FDA or EMA approval, but they may be helpful to marketing in countries (like Germany) where no marketing license is required for autologous therapies. Whether the marketing claims this data support are adequate to have an economically sustainable business is a different question.
Me:
You seem very knowledgeable but once again why cannot you see the forest for the trees. Yes you did see some one-off points (a few trees--the HR 0.99, 0.98, and 1.00 from the three charts you interested) but forget the forests (the general, clear separations of curves--overwhelmingly more representative HR 0.63, 0.78, 0.74 respectively).
Note: the reference here are data of those patients who were treated with the best of care or standard of care. Not because an one-off point which is within the calculating error or even it's true, the FDA would be too scared to do its job.
BTW, FDA would look at the whole picture besides HR and p-values which clearly show efficaciousness, but various other factors: some will come when the publication is released, some like "failed" PFS which in the eye of any un-biased, knowledgeable person and FDA is a clear sign of DCVax-L is working, and the other clear and beautiful separation of DCVax-L for rGBM compared with control with HR 0.58 and P-value <0.001.
One other "forest": Over the past 17 years there have not been any trials but DCVax-L trial which has showed significant improvement in patients OS in nGBM, and over the past 27 years there have been no any trials but DCVax-L trial which has showed significant improvement in patients OS in rGBM.
So you want to delay this vaccine to get approved, and add many more years to the unnecessary human suffering? Or you want a big pharm of your association or not to take over this company cheap?
Disclaimer: I am a long-term investor holding well over seven-figure of NWBO shares. Just on the day of presentation on 10May 2022, I added well over six-figure of shares, with first batch in the range of $1.2-$1.3, and the second larger batch in the range of $0.3-$0.4. Part of the purchase was funded by my selling of about 10% of my holding days before the presentation. I am once again top my holding.
Hodag:
Dan, I am looking at the forest and from the FDA's perspective there are a couple of giant redwoods standing between NWBO and approval. I have taken multiple products through regulatory processes in the US, Europe, and elsewhere, and I know what kind of things the agencies ask about and what statistical arguments they accept, and which draw all manner of skepticism. I have gone into more than one regulatory meeting with better stats than these and left those meetings battered, bruised, and bleeding. In particular, the level of scrutiny the regulators apply when applying for permission to conduct a trial is orders of magnitude less than what they do when a company applies for a full marketing authorization.
If you are so confident that NWBO has a slam-dunk approval decision waiting based on this data, then by all means invest your life savings. This is still a free country.
Me:
I love free country, and believe the collective wisdom (more) than any individual ones.
Look at what setting we are in. For nGBM, let alone rGBM a merely 2-month or 1.5-month of improvement in OS in the past had got drugs approved, which happened decade or if not decades ago.
It's simple do you believe DCVax-L is safe, does it demonstrate some officiousness for the indication concerned.
Guess, the first is a check, the second I say yes and of course you say no.
After all, it's RAs which will make the decision.
My investment is based on I do believe DCVax-L will get approved, at least in other countries if not in US, for at least nGBM or rGBM.
If that happens, a floodgate is open for other good things to follow.
thank you for your comments. Not intended to offend anyone else in this board, you are the only one I read when I come to this board from time to time.
My personal experience yesterday:
First, my understanding of the reason why we have revised/updated SAP, endpoints is explained in this plus-one post of mine written just before the eve of Xmas 2018: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145658266
As a result, I have always anticipated "our good friend" the hitman AF will strike again, supported by the naked short cabal with perpetual theme that the trial had failed, Linda had hidden the failure for years. His two tweets leading to the event has heightened my alert, and I knew it's coming.
So I sold about 10% of my well over sever figure's holding at $1.9 range days before (note it’s my first selling in quite a long time), explaining to my wife it's just technical, not that I have lost a shred of confidence in this company.
While quickly skip-reading the slides presented by our good doc musella at https://forum.virtualtrials.org/dcvax, I am totally wowed by the data I have seen; on the other hand my screen also showed the sudden declining of share price. I said to myself WTH, I had to buy, not expecting the price that could get hit this hard. So I bought about 100k shares at about $1.2-$1.3 range, thinking this was the bottom.
Of course it's not. The unbelievably quick downward spiral of price ensured all the way from $1.2 range to $0.3 range, it's just unbelievable for pete's sake! Realizing it's not just panic selling from innocent traders/investors it's truly something sinister happening. I had no doubt it's the work of naked shorting cabal who started the panic. Quickly logged in my accounts again, placed orders one or two cents above the ask. Alert was coming right away: the orders of a total of about 150k shares were filled in the range of $0.4-$0.5.
After that the price quickly recovered all the way up to $0.96 when the anticipated hit piece from the hitman AF plunged into the public view, emphasizing now obsolete no-longer-an-endpoint PFS while intentionally ignoring both primary and secondary endpoints which are met handsomely with very statistically significant manner. The price instantly suppressed in coordination, and we ended at $0.76 at market close yesterday.
Don't think the unfolding of the days leading to yesterday and yesterday is anyway natural in terms of stock trading, or retail panic behavior. Yes they are part of it, but I have no doubt it's the naked short criminal force who have orchestrated it among them AF just served as a foot soldier.
With the stellar data now known to the public, I strongly believe the greatest risk in investing in this stock has been removed. I can finally say we are de-risked, and the price will be once again on the rise, this time with more steady hands, and no doubt I DCVax-L will get approved by all RAs involved for both nGBM and rGBM, despite it taking time, not saying there will be a smooth sailing ahead, but definitely we will be there.
A delayed party is sweeter.
GLTA
AF after this event will be put in a footnote: he had done a great deal of damage to this company, hereby hinder the development of this disrupted, innovative and efficacious vaccine technology, potentially help "kill" a large number of patients; and
AF and his master naked short cabal will be no longer formidable, negated increasingly by public awareness and understanding of the stellar data.
For those pros and amateurs who have had doubt on naked shorting or short manipulation of nwbo, today serves as a wake-up call.
Rest assured, Northwest Bio will fight back. DCVax-L will be approved for both nGBM and rGBM.
Then this is huge. Glad I bought
Who have bought shares this morning? Let me start:
Arh Dan
@Arhdan9
·
12m
$NWBO, $XBI
Grabbed 100,000 shares from the short this morning ranging in price from $1.25-$1.35. Wow, thought I have done it. Keep the good work shorts!
You are only talking one story of the short, there are many other stories which will be most significant.
The naked shorting cabal will inevitably become part of a huge success story of Northwest Bio, its vast numbers of retail investors, the patients, and mankind advancement in combat cancers, etc
Investors shall aim high, much higher price, taking into account of current market situation that the winner takes all, plus naked short BBQ meat!
The FED having repeatedly failed in policy has been forced to tightening, and if it really wants to control runaway inflation, the FED has to resort to much hawkish stance.
While the market is depleting with liquidity, a small number of companies like NWBO when confirmed will drawn in most of the liquidity which is widely available now sitting on the sideline.
As a result, your usual valuation of NWBO should be adjusted multiple higher, ie, if the price is $5 after positive TLD, now you should think move that price much higher.
It's a natural thing that the winner takes all!
yea at least the short can finally serve a purpose: Delicious BBQ!
First, fool the short, then kill them. Then, smoke out the naked, and kill them as well.
Justice served.
Just wrote to event organizers asking them to accommodate Linda Liau's presentation featured, and Linda Liau as a keynote speaker. Cheer
This is my last post for today as a reply to your post:
From my decades long biotech investments, I don't see a biotech company in a phase III trial can easily go away, ie. bankrupted right after a binary event.
Most often, the company would lose the ability to raise funds at reasonable share price, and could only issue vast numbers of shares at very much lower price (like %50-90 lower) with huge dilution to the existing shareholders. And such company after failing the trial could mostly find something else to "hype" (see cvm as an example), and may survive with multiple RS in the span of years thereafter, meaning more dilutions.
The point is they could survive but just in a very bad shape for existing shareholders.
So I don't think a financier before binary event would have a really high risk of not getting money back after the event if it goes badly. They can easily get money back from money raised from huge dilutions of the existing shareholders.
The above of course is not remotely applied to NWBio, since even in the worst scenario which is we would miss the primary endpoint, NWBio would survive for some secondary endpoint (like CVM), let alone we have DCVax-D awaiting for development (or "hype" if you will if we were failing in L, which I have never thought is a remote possibility).
All in all, I don't think it's a problem for John to get his money back even we would experience the worst case scenario.
I have all confidence in my investment in nwbo, and my shares and my family shares have repeatedly peaked.
GL
[I would add it's obviously both Linda and John have developed rapport and are friends. So I don't have any doubts on the deals signed today]
Hi CapHillGuy, I don't think this draft guideline has any immediate meaningful bearing on NWBO to release TLD. NWBio will release TLD/publication whenever it is possible. But by a quick look at it, it seems it puts focus on various uncertainties in drug/biological product developments and approvals, such as flexibility weighing on high safety risks over efficacy. In that sense, not really a concern for NWBIo's DCVax-L, since it has been proven very safe.
Nonetheless the recent regulatory developments including this draft and the one called "Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products Guidance for Industry," etc, seem to be very favorable regulatory developments for drug/biological product approvals in the future. That is good for NWBio and I believe it also good for CVM as well.
GL
Synopsis of Linda's New Favorite Financier John M. Fife (Owner of Iliad Research and Trading, L.P., Streeterville Capital, LLC, etc.), the Three Financing Deals
Both John and Linda are graduates from Harvard Law School with a JD.
John seems to have been known to the Wall Street as a toxic financier, and has had prior lawsuits against him for manipulating the market or distortion.
NWBio has so far had three financing deals with John (see the relevant excerpts attached below for reference).
Both Linda and John have a parent died from cancer.
All three financing deals with John, i.e., about $5.5 million promissory note on 14 August 2020, about $11 million loan on 1 March 2021, and about $15 million loan on 22 Nov 2021, are of good terms (not toxic by any book or practice), despite his toxic financier reputation on the Wall Street.
It is of interest to note:
1) It's only after June and August 2021 when NWBio entered into multiple four-month notes with various individual lenders (John may not be part of it) for a total of about $3.3 million, which included the right to purchase (exchange for) shares at price of the next offering at 12% discount (note it's called Next Offering, not the first offering after TLD/publication), that John's loan on 22 Nov 2021 appeared to have the similar direct share purchase (exchange) term for the first time. Also be to noted in the deal the event of TLD is specifically mentioned;
2) In the March 2021 loan, "The Loan Agreement allows prepayment at any time at the Company’s election. If the Company elects to prepay, the prepayment would include a 10% charge" while in 22 November 2021 loan "The Loan allows prepayment at any time at the Company’s election," So it appears the former loan if prepaid would cost the company 10% charge while the latter loan would not charge company for prepayment, but instead, it gives the lender the right to exchange for share at discount if TLD is announced and there is offering of shares after that; and
3) The 22 Nov 2021 loan for the first time gives the lender John the right to exchange for "common shares priced at the price of the first private placement transaction following TLD less a 12% discount and to purchase another 50% of that number of shares at the same price. This then-springing right expires 14 days after the post-TLD private placement."
So it makes sense the reason that there would be no payments due for the first 8 months of the Loan term. Because of the share price exchange term, if I were John I would prefer the period of no payment as long as possible, for example, I would prefer 12 months, instead of 8 months, so that when TLD is announced I can be sure all my money is intact, ready for exchanging shares at 12% discount of the price of the first offering. This deal in and by itself for this reason is positive indication of his belief on positive trial outcomes, and is essentially intended for exchanging shares at maximally as possible at 12% discount of the first offering share price.
On the one hand, obviously it seems John wants to be a big shareholder of NWBio, and he has been kind to the company in providing much needed funds; on the other hand, it is understood he wants to maximize the return of his investment, and he can achieve that by 1) his $15 million loan deal with the company which gives him the rights for exchanging shares at discount (this is a fact), and 2) I suspect John and/or his associates might have already well dispositioned a long time ago in this endeavor.
I further suspect John and/or his associates might have been part of the force behind the recent month-long steady share suppressing activities, coincided with a large number of warrant exercising for shares with which at least part of the shares have been sold.
Obviously John wants the share price as low as possible. Nonetheless market is very fluid, dynamic and unpredictable, with always a myriad of forces with various interests acting and counter-acting on the market.
So it's yet to be seen in what direction the price will be trading. Personally I believe it will regain traction and heading north, because there will be milestones on the horizon, including TLD/journal (the 8-month no payment term means nothing in this regard, please refer to what I have said re it above); the share price can only go as low as it practically can. At the current price I think it is almost as if the trial would miss its primary endpoint; and this $15 million deal actually reveals a lot. I don't believe John had a look under the hood before he reached the deal with the company, but the deal by and in itself makes the deal even more bullish for the share price.
Buy as many shares as you can afford!
Excerpts of related financing deals below:
Promissory Note Issued for Loan Made By Iliad Research and Trading, L.P.
On August 14, 2020, Northwest Biotherapeutics, Inc. (the “Company”) entered into a Note Purchase Agreement and Note (collectively, the “Note”) with Iliad Research and Trading, L.P. (the “Holder”) in the amount of $5,505,000. The Note has a maturity of 21 months. There are no repayments during the first 7 months of the term. During months 8 through 21, the Note will be amortized in monthly installments of 110% of the pro rata principal amount. Interest on the Note accrues at a rate of 8% per annum, and the Note includes an original issue discount of $500,000.
The Note contains customary default provisions, including provisions for potential acceleration of the Note and default interest
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On March 1, 2021, Northwest Biotherapeutics, Inc. (the “Company”) entered into a Commercial Loan Agreement and Note (collectively, the “Loan Agreement”) with Streeterville Capital, LLC (the “Holder”) in the amount of $11,005,000. The Loan Agreement has a maturity of 22 months. Repayments do not start until November 1, 2021.
Following November 1, 2021, the Loan Agreement will be amortized in 14 equal monthly installments of principal at 110% of the pro rata amount, plus accrued interest. Interest on the Loan Agreement accrues at a rate of 8% per annum, and the Loan Agreement includes an original issue discount of ten percent. The Loan Agreement allows pre-payment at any time at the Company’s election. If the Company elects to pre-pay, the pre-payment would include a 10% charge. The Loan Agreement contains customary default provisions, including for potential acceleration.
The funds will be used for the Company’s ongoing business operations.
------------------------
Between June and August, 2021, the Company entered into four-month note agreements (the “Notes”) with various individual lenders (the “Holders”) with an aggregate principal amount of $3.3 million for net proceeds of $3.1 million. The Notes contain a conditional piggy-back right to independently purchase shares from the Company, which provides a right for the Holders, contingent on the release of clinical trial data and a next private placement offering (“Next Offering”) after this release, to (a) purchase shares from the Company within seven days following such Next Offering at a 12% discount from the share price of the Next Offering for a variable number of shares equal to an amount up to 50% of the principal amount of the loan (the “Contingent Right”)and (b) exchange some or all of the outstanding loan amount for a variable number of shares, within seven days after the Next Offering at a 12% discount, resulting in a reduced cash amount repayable under the loan agreement (the “Contingent share-settled redemption feature”). The Company accounted for the Contingent Right as a freestanding financial instrument, which was classified as a warrant liability at fair value on the Consolidated Balance Sheet with changes in fair value recognized in the Consolidated Statement of Operations. The Company accounted for Contingent Share-settled Redemption Feature as an embedded derivative liability at fair value which requires to be bifurcated, and with changes in fair value recognized in the Consolidated Statement of Operations.
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On November 22, 2021, Northwest Biotherapeutics, Inc. (the “Company”) entered into a loan financing with Streeterville Capital, LLC (the “Lender”) pursuant to which the Company received net proceeds of $15,000,000 (the “Loan”). The Loan has a maturity of 22 months. No payments are due for the first 8 months of the Loan term.
Thereafter, the Loan will be amortized in 14 equal monthly installments of principal at 110% of the pro rata amount, plus accrued interest. The interest on the Loan is 8% per annum, and there is a 10% OID. The Loan allows pre-payment at any time at the Company’s election. The Loan documents contain customary default provisions.
Upon announcement of the top line data (“TLD”) from the Company’s Phase III clinical trial of DCVax®-L for glioblastoma brain cancer, the Lender has a then-springing right to exchange the outstanding balance of the loan for common shares priced at the price of the first private placement transaction following TLD less a 12% discount and to purchase another 50% of that number of shares at the same price. This then-springing right expires 14 days after the post-TLD private placement.
The funds will be used for the Company’s ongoing business operations.