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If they have to change the Brand Name (R) once approved and marketed, I vote for
Phoenovix DC(R)
I can see the pipeline chart now
Phoenovix (R) for GBM - - / - - - -
DCVax-L for MCC - - / - -
DCVax-L Ovarian - - / - -
DCVax-L Lung - - / -
DCVax-L RCC - - / -
DCVax-L Liver - - / -
DCVax- L Bladder - - / -
DCVax- Direct
Pancreas - - / - - -b
Sarcoma - - / - - b
Ovarian - - / - -
Breast - - / -
I seem to have cops working for me now.
My colleague here doesn’t need to play cop. I also seem to have outside counsel hanging around, some guy from Texas, I believe and I hear…you know…they like their $ettlements BIG in Texas. It starts with an investigation by the Justice department so I am speculating here and this would mean the cops are already on the case, you know, the forensics cops that is if the investigation happens to involve this stock, for a company ran by a former lady of the Executive Branch and her buddy also from the Executive Branch.
Vator, here is what I am seeing.
LP seems to know someone that knows their way to work with the US Patent office, LP worked in the Executive Branch, obviously. She certainly seems to know a lot of wealthy friends who weighed in and seemingly gave what was needed when it was needed and had her back once the March to the finish line began. She hired consultants to work with the regulators, a former consultant from and for Canada with purpose, consultants to work on uplisting and staying current with filings, made peace with SEC, lets not forget brought on board the former head of a CIA investigation department. Did I mention LP worked at a high level of the United Staes of America’s executive branch.
The question is does she or any of those people know people in other executive departments? Some day Agriculture may be of interest but for now lets stick to humans. Well, Justice would sure be interesting…hmmm, what about…now this may seem crazy…what if she knows people at the Food and Drug Administration. I am not saying anything nefarious but it never hurts to know your way around a department through connections, any department, any where in the wotld.
Now, that is just crazy talk and wild speculation. You know somethings are called speculation but maybe that isn’t quite the right way to look at it when a team of specialists analyzed data from their fields and got synthesis and insights from experts in other fields. Then there is speculation which is also a guesstimate of probability, and finally wild speculation before conspiracy. There are a hell of a lot of conspiracy theories running wilde everywhere today, but judge yourself how crazy any of that above sounds.
Sashi Murthy…dun, dun….dun dun dun… Sashi Murthy… dun, dun … dun dun dun
Yep, forgot NIH, how could I forget NIH.
So I know this person…he is involved in analyzing on the shelf programs at a US bases which aren’t confidential. You can acquire rights to these patents and incubate industry in that state.
The question for whomever that party pooper dumping on the Joy of a patent holding a government name as well…tell me why that matters, please? Or rather, I would prefer to hear from one of my long colleagues?
Senti,
Did that shareholder meeting preceed about March of 2015 or a little bit later or was it after the fact?
Double, blind - the physican and the patient know not what treatment you have received. There are times a drug cause an adverse effect that ‘unblinds’ some doctors and patients to treatment. This knowledge has an impact of the trial and while sometimes mistaken when actually placebo, it still gives them strength to know they have gotten the gold ticket, not the brown one.
Point being, this is why all around them must be blind to the treatment allocation. The impact of placebo affect and its inverse are well established. Even though NWBO may have had a reason to believe they knew the cause of the halt in new screening, they would not have verifiable knowledge. They would not have know how things proceeded and they would not have known who got what…even the 32 plus moved to treatment. Every patient remained blind.
Now just what was the data requested by FDA in 2015 and how much of a clue did it provide Linda? It didn’t seem like a long turn aroun as I recall.
My guess, case records for patients who have died. Maybe of the open label arm too. This could have also told them more than a reason, like progression status in patients who died. We could use the KM and all the data provided to recreate a guestimated number of deaths at that point in time. Suppose as an example…
110 death had occurred and the blinded monitors see roughly 55 in each blinded group. Hold it…time out…blow the whistle and through the flag. It works placebo must go. Not before taking a look, examine those cases. Ok, check, check, check, check…
Wait Aaron, yeah Joe, did you notice all of the placebo death have occurred early, but the treated patients we have that died have all already lived longer than expected, you guys know what that means, what Sharon, that everyone is living longer even those that die. Holy shit your right. Call FDA.
Instantly Germany…Halt, Halt, Halt…
Flipper, thank you! BTW… eye opening.
This was my favorite one because…I did not even know this much less put them all together. I must have skipped those days. If you have a link, please share.
12. Dr. Liau recently acknowledged (2022) cell immunotherapies have been challenging in the past to manufacture. A year prior, she stated we’ve got to find a way to get this treatment to patients.
You know, his name fits great into a cheer.
Shashi Murthy…dun, dun…dun dun dun…Sashi Murthy… dun, dun,…dun dun dun…Sashi Murthy
Why didn’t we have pep rallies for really smart people too?
Remember this date? It looks a little different since Bigger and others dropped that Kaboom of a government investigation now, doesn’t it?
Imagine where Direct would have…BTW… when will they give us final or updated Direct phase I data?
19
OCT
2015
NW Bio Issues Statement on Highly Unusual Trading Activity
Reiterates Encouraging Clinical Data;
Sees Coordinated Shorting Campaign
BETHESDA, MD, October 19, 2015 – Northwest Biotherapeutics (NASDAQ: NWBO) (“NW Bio”), a U.S. biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, today issued the following statement addressing the recent highly unusual trading activity in the Company’s stock:
NW Bio is not aware of any fundamental reason for the substantial decline in the price of the Company’s stock on Friday, October 16. Indeed, NW Bio presented encouraging clinical data at scientific conferences in London and New York as recently as mid-September.
The Company’s clinical data update included promising ongoing interim survival data from both the Phase I trial of DCVax-Direct in 13 diverse cancers, and the Information Arm of 51 patients who were unable to enroll in the Phase III trial of DCVax-L for newly diagnosed Glioblastoma multiforme (GBM) brain cancer because of apparent early tumor recurrence.
In the DCVax-Direct trial for patients with multiple inoperable metastatic tumors who had failed standard treatments (including multiple different chemotherapy regimens), half of these patients are still alive with survival times now ranging up to 22 months, exceeding expected survival times.
In the DCVax-L Information Arm, for the 25 GBM patients with apparent early tumor recurrence at one of two time points, 40% of the patients have now reached or exceeded approximately 3 years’ survival. This substantially exceeds the expected survival time of about 15 months even for regular GBM patients without early tumor recurrence.
NW Bio noted that the Company’s shares have experienced highly unusual trading activity since the September release of positive data, including especially on Friday, October 16, when more than 2.9 million NW Bio shares were traded, representing five times its recent average daily trading volume. The Company believes this activity is part of an ongoing effort to drive its stock price lower through an orchestrated campaign, including questionable short selling activity. The Company is intensifying its investigation and gathering of evidence.
How do you survive if some entity like that decides to sink it’s teeth in you?
My guess is that one way is to know a lot of wealthy people who actually trust you and mix that with some very strong government connections (I am talking executive branch), Then add some good attorneys to your team both inside and out. The real trick though my guess would be to keep marching forward with your business plan while also dealing with that dirty work that is oh so scummy but essential to the penultimate success of your plan. Now if you could just figure out how to time it all so that everything works out right. If you can do that you should probably add the credentials Grand Master to your signature line.
This may help find the path…
Flipper…amazing puzzle piece fitting. You put that all together and what do you get… a plan that began with the ingredients pulled together 8 years ago, the preparation done 7 to 2 years ago, the baking over the past 2 years and the masterpiece revealed very very soon filling our cornucopias for generations.
This all reminds me of a leadership development game that was used to learn about the importance role players and specialists… the Viking Legacy.
You do a personality test,one that was not Jungean based. Then teams of about a dozen get divided, two with all similar types, but one yin and one yang. Then a third with Yin, Yang and a collection of the unique specialists. I am Pioneer and an Omega. I lead from the back of the room, not the front where Alphas play.
Anyway there are like 800 cards with like 200 of value. They contain facts, dates, pathways, etc. You need to identify where the viking hoard began, what route they took, what were the dates of the journey, and where did they settle. The third group ALWAYS crushes the first two, sometimes hours ahead, sometimes the first groups can’t even finish.
This board is the third group. The A-type team usually looses to the analytical types who take forever.
Biosect, Thanks for the color you added here. The clear reasoning as to why you believe Germany initiated the halt seems likely to me. I assumed that FDA told them they were investigating deaths without much specificity, but this seems more plausible. I have always been aligned with your German rational regarding conduct of human trials, I just don’t think FDA is all that far behind on scrutiny over patient safety issues. So to me, it didn’t matter which but this sequence passes the Occam’s Razor test, understanding that doesn’t mean it is right just the most likely rationale.
I stand differently regarding the 32 because that one to me is beyond most reasonable, there are no other reasonable explanations.
Hi Doc, I think that I am following this post and you concur that NWBO did not initiate a trial design change.
As a reminder to others, FDA halted the study. That means they were involved. NWBO couldn’t make changes without their approval.
Just to add more detail…
IRBs… to believe a voluntary change in protocol occurred is to believe over 250 IRB staff, 80+ investigators and countless sub-PIs and research staff are all aware of this protocol change and for seven year not a peep from anyone. Am I really being asked to believe this has occurred?
IRBs folks, you can’t just F around with your trial in a vacuum.
I have a solid memory, but I can’t recall the dates and times, and I am not about to read through my history to find these. Sorry, AeK. I believe Biosect has also articulated this theory, maybe he is willing.
Addressed in my reply already.
FDA does not swing from the hip. Add patients to your study or change primary endpoint or both.
Decide an ECA is an acceptable, approvable design when a validated database does not exist…implausible.
Change your only pivotal trial design voluntarily for your lead asset with no existing product portfolio, please explain how this is not material? How about after data lock?
Sorry, bonkers
What facts am I missing that I need, exactly? Which labs am I missing? To call the diagnosis a misdiagnosis, you need a plausible alternative.
Plausible options, there are none
Reefrad, Before I give you any leeway here in my mind, answer me this.
Just how did the company become aware that treated patients were having pseudoprogression? I do have a suggestion here but it leads you down a long trail of inquiry AND this requires FDA agreed to an ECA before seeing a validated data set for the ECA… super, super, super duper risky move which would have been voluntary if you want to say it was because of the adaptive design that allowed this. Remember, this has not been done before, it assumes FDA would agree to an ECA after a very short review of data without validation (you lost me here), and even if external data suggested the issue was a problem the study was already powered to detect a difference on OS. The standard process if you believe after an interim futility analysis that your study is not futile but may not be able to detect a difference as currently designed is to expand the enrollment, not reduce it…
Without an interim efficacy peek, you are asking me to believe FDA would agree to a radical new trial design that has not been validated, based on conjecture from open label patients that you MAY have an issue, and acceptable techniques to address this were avoided for this new pathway which again has not been validated yet. Sorry, not plausible.
Why would this company driven, highly risky change to design and protocol (…IRBs again) not be a material event that must be disclosed to investors that would as a result be waiting 7 years or more to learn of this change after TLD is released?
Unfortunately, I do not think you can do better than this, but this was a great shot on goal…just not good enough to get past Eddy Belfour on a bad day.
Senti, what I am telling you is the idea that this misallocation was spread out over 10 years is not possible. Do I need to describe simple block randomization? Picture the first 20 patients being skewed 15 vs 5, guess what happens during the next two blocks of 20.
The more complex acceptable randomization techniques only go further in making sure balance by all available parameters is maintained. A 32 patient skew by randomization is impossible.
Either FDA did not allow the final 17 patients randomized to placebo in the trial (highly, highly doubtful) or they removed placebo. These are your options to get to where we landed. The company, patients and physicians would be completely unaware of what took place, officially, thus integrity of the blind maintained. How regulators choose to view the population is up to them, but the Intent to Treat was DCVax alone for the final cohort.
Anyone believing that an error n the randomization schema occurred is not living in the 21st century of clinical research, no offense intended.
The UK will never be covered by ocean, the same cannot be said for the Florida Keys, the Cook Islands or Aruba though
No one aligned to my theory has ever indicated that FDA or any other regulator looked at the blinded, randomized data as far as I recall.
The theory is that they looked at the unblinded deaths……as they always can do.
How else do you think they typically halt a trial for safety? This can be some other serious adverse event other than death too, like say severe encephalopathy, as they halted the original beta amyloid vaccine.
Pseudoprogression caused the halt theorists…
Please tell me how exactly weakening the power of a study will help overcome any confounding that pseudoprogression may have caused?
Things that make you go, hmmmmm
Exactly…FDA has had their footprint all over this study. If people choose to believe what Ex was selling you, and ignore these tracks, then by all means go ahead and believe his theory that FDA hasn’t bought in to the SAP.
My guess is that they actually were collaborative in the development of the SAP offering input along the way. But you can always believe in good old Ex, & his comrades like Gerry Soupcan and LC Y2K. I recall them warning me to bail out at $0.24 and even $0.14.
Diagnosis of exclusion…if a rational explanation is offered and other explanations are eliminated, then you have your answer.
If patients and or physicians were to know that treatment was altered in any way, the company would then also know, and that destroys the integrity of the trial. It is the CRO that administers the blind.
Block randomization or some enhanced version of this has been a standard in large scale regulated clinical research for literally decades. This is done to ensure that randomization is as close to balanced as possible.
To have an imbalance of 32 patients and the events that transpired post August 2015 halt can only be explained this way. If you have another possible explanation, I am all ears as I have been every single time I have thrown these theories out over the past 4 years. No one can come up with a plausible explanation. Ex and other have tried and were blown to smithereens. Maybe you don’t call this fact,,, I suppose that could be considered by some a judgement call. To me, the verdict has been delivered.
I know you can find the 2017 JTM article yourself.
And as a reminder, to force an imbalance in this way dramatically reduces the power of the study. 331 patients randomized 2:1 is more powerful than 2.34:1. Meaning the power to detect a difference between two groups statistically.
I am one of the originators of this thesis. In my thesis, neither investigators, patients nor company knew that placebo was removed. BTW this was my thesis in August of 2015 which I shared with everyone invested as a connection with me.
Evidence to this thesis is the FACT that the final 31-32 patients were only placed on treatment, no randomization to placebo. While this only directly ties to those not yet randomized, the rationale to do this creates a moral and ethical obligation to treat every human being who volunteered their life to the study of a potential therapy. There is an obligation to those patients to first do no harm and to progress with GBM is to die, at least if they stay on placebo, and at that point it is not known whether or not DCVax can rescue a portion of them after progressing, it was only known that it delays death before progression.
Ding, ding, ding…
When the rams line up to butt horns, those that do not humbly accept defeat are banished from the pack when the alpha ram is so dominant.
Biology has its predictably .
SOS was extremely conservative all around in this rendition IMHO. For example, he uses 20 in 100 as the estimated survivor rate at 5 years on DCVax. Let’s look at this a little deeper.
Over 28% of all patients survived at 3 years which was up about 4 percent from an analysis done a year and a half earlier. Using the data provided on predictive survival in both the article and SNO presentation, one can extrapolate the 5 year number of the combined group to be about 19% with the likely continuation of the phenomenon that later enrolled patients will pull this number up, I believe to about 22%. These are combined group numbers however. Using reasonable estimations for placebo, these produce about 35+ and 25+ In 100 treated patients survive at 3 and 5 years respectively. That creates a delta vs placebo which is about 5x natural history at 5 years which included IDH patients.
What are we invested in an ancient pharma with little pipeline and future headwinds or should our multiple valuation look more like a burgeoning biotech with a deep pipeline and novel approaches to disease with high unmet medical need, very, very high unmet need.
Ex is leaving because he sees the writing all over the walls throughout every room of the house
Thanks for the date clarification. Hard to believe that FDA lifted the halt 5 years ago now, but FUDsters still try to spin the 2015 new screening halt with continued enrollment and treatment as some death nail, when there is no halt anymore.
What a crazy messed up world we live in today where purveyors of alternatives to truth carry such loud and influential voices.
Thanks, Poorman. This seems to make sense to me. I think DI shared thoughts with board members that seemed to suggest Flashworks may be leverage in contract discussions. Do you think this patent could be relevant there?
Maverick, spot on!
I have seen positions open now for way too long, and I don’t even want to elude to the salary and benefits packages we are talking about because I don’t feel any desire to explain. Suffices to say, skilled labor is incredibly tight in Biopharma.
Given all the progress and positive developments over the past 15 months, there is no way NWBO plans to go it alone in the United States, maybe UK and even Canada, but it cannot happen in the US. Our market is incredibly complex with liability everywhere. You need a huge machine of operations talent and this drug is very complex in its manufacturing and supply chain dynamics, not to mention the billing nuances of mixing medical and pharmacy benefits.
Partner or BO is coming shortly after approval which IIMO is pending.
Many times I have stated here my conclusions as to the screening halt. Several others with deep experience and knowledge in this realm concur.
Some time during the Summer of 2015 the Data Safety Monitoring committee called for a study halt, but the company decides and decided to continue on with the trial. Since the reason for halt was not a safety or manufacturing issue with DCVax, FDA and other regulators allowed this, but required changes to the study design which removed placebo from the trial. (IMO this includes both patients in screening going to go on therapy AND patients in trial currently receiving placebo)
Death is always an unblinded safety event reviewed by the DSM. I have never heard one credible explanation other than that the DSM saw a clear increase in death among placebo treated patients and called for a halt. No IA needs to be performed to see efficacy on OS, but that does not mean if you stop at that point you are guaranteed approval nor does it mean you will have marketable data for commercialization which can help you gain and maintain a clinical advantage and become SOC. Thus LP, chose to march on and the rest is history.
The history of the greatest step forward in oncology since who knows what if anything.
I think it is time hat I revisit this piece of artwork…thanks to whomever…
Maverick, that explanation seems to connect a lot of dots between what DI has said about Flashworks related to Cognate, what the 10q’s have said about the manufacturing of DCVax around the world, and where I believe things sit from a regulator perspective.
That contract may be all that rests between the American people and access to DCVax.
You know the DCVax(R) Personalized Dendritic Cellular Immune Therapy for the treatment of Brain Tumors which provides long tail survival by overcoming tumor defense systems against individuals immune response… Or so I am told by Northwest Biotherapeutics.
Someone should post that design schematic on our home page. It is nearly as beautiful as that dendritic cell image.
FLASHWORKS
It is almost comical to continue to read doubt and FUD. When the CAN of FLASHWORKS opens up on them, they will be lost in space.
Since we didn’t see a delay in the randomization and treatment of those last 32 patients, then no changes to the patient consents could have been implemented because to draft them, push changes through IRBs and call all patients back in for signature and consent takes quite a bit of time. Even if they rushed every single step through, we would have seen a fairly long skip in time, but we did not.
Therefore, no change in consent, no change in IRB status, no change in IB, and that means no change in the known safety profile which includes lack of efficacy.
A demonstration of competence in the face of significant criticism that management is clueless, shoots from the hip, and ignores SEC rules and standards
But I expect you to spin everything negatively. Thanks for your consistency
Biosect, I believe that you and I are of like minds when it comes to appplying this SEC rule to biopharma companies. Although there is a nuance that I may come back to ask you about.
I am interested in your views on a tangent from the current discussion. Shorts state a belief that an IA was performed and they know the trial has failed, but continue to perpetuate a scam. This actually forms the basis of most short-side theory. This, however, cannot have happened, and forget SEC.
For this to have happened, it would have occurred before the August 2015 halt in new screening and here is where that argument falls apart. Investigators brochures must contain updated safety and lack of efficacy data. Evidence of lack of efficacy would require patient consents be updated which requires IRB approval. These policies are governed by regulators and are in accordance with Geneva Convention international law. If they had knowledge that the data showed lack of efficacy, then patients in screening would not have been put on drug prior to the changes being implemented and IRB approved. Same is true for any patient currently receiving active drug post-randomization. On top of that FDA lifted the halt in 2019, and a new trial involving all patients receiving DCVax with or without a combined previously failed therapy. Meanwhile LL promotes this trial to her colleagues and accepts referral patients.
These are human clinical trials regulated by all 4 governments and not some experiment on rats in a lab.
This post should get a bookmark…thank you Lykiri, Senti, DD and Michael Bigger!
He won’t go away. He will just lay low a couple days before return to spout half-truths.
The mixng of fact and falsity is a trick that has been used for several years on this board. It makes the statements seem credible when they are not.
I will be laughing my way across the globe in early retirement.
Thanks for this intel, Senti. If they never had an SAP, you can pretty much assume FDA has had input on the one created after 2018.
On top of what you say, the company has stated multiple times that NO INTERIM EFFICACY ANALYSIS WAS EVER PERFORMED.
The bear thesis is absolute bunk, and by now they know it.
Longs need to ignore stock price and the psychological games they try to play with it.
As well, the study protocol changed in 20015. Therefore, the SAP needed to be finalized after 2015 at some time. Waiting for the study to complete makes the most sense.