Did you read the blinded paper or just take others’ word for it?

At the time of the blinded data publication, I worked up the possible results myself, with error bars, taking into account standard outcomes of the time as a control, and figuring out what ratios would be likely, probable, or possible. There is a good shot at trial success and much reason for optimism, but again there is also room for ambiguity and even possibly failure with respect to primary trial endpoints. It isn’t a slam-dunk.

Clearly some people on the board have different tolerance for risk than others, and I am on the risk-averse part of the line. But why do those who are comfortable with risk feel the need to respond derisively to my concerns?

Thank you kindly, Dr. Bala, for your substantive and topical reply.

I hope you and your loved ones are well. Our family are all fine. I am pretty sure I already mentioned it on the board because I was desperate at the time, but a couple years ago my husband had a grand mal seizure for the first time in many years. We were sure it was the beginning of the end, a sign of tumor progression. But after all the emergency tests and exams, the neurologist said the episode was just a side effect of the hole in his head — woo hoo! In fact, he said he didn’t expect the brain cancer to return at all!!! It was the first time any doctor had ever told us anything remotely positive. We were and still are ecstatic. And then, a month later, the pandemic lockdowns began. LOL. But we’ve been getting through the pandemic without incident.

The upshot for anyone with newly diagnosed brain cancer: go to the biggest big-name medical center you can get to, such as Johns Hopkins, the Mayo Clinic, UCLA, King’s College in London, and so on. We are so grateful that our friend advised us, after my husband’s first seizure in 2011, to quickly move on from the local hospital where the neurosurgeon was more of a spine specialist and thought probably he could “feel” where the tumor would be.

Well, Jim, until the results are released, you really can’t prove it. No one can.

If you yourself are perfectly secure in your beliefs, why are you so angry at my questions and concerns?

I’m not sure what you mean by “troll.” I’m a longtime NWBO investor (since Halloween 2012, almost a decade) with a husband who is a brain cancer survivor. I do get tired of the aggressive pollyanna-ism on this board, but sometimes I check in to see if trading activity reflects any plausible rumors, durable rumors, or both.

I do think it’s irresponsible to invest — and especially irresponsible to goad others into investing — based on feelings and conjectures.

But I’m not judging. It’s exactly what I did, when the message board discourse was pretty much as it is now, and look where I’m at. I went from Pollyanna to curmudgeon myself.

Have you seen the trial results? I haven’t. Until we do, no one knows whether OS was improved.


“Boy what contorted FUD! Did you proofread what you posted as logic to turn obvious exciting news into something like never mind improving OS with great safety and virtually no major side effects, a total cure is a lifetime away?????

“Please consider - Some people wait a lifetime for a moment like this !!!

“Would make a good song wouldn’t it ”



I, too, would love to see a cure. My husband is a Grade III anaplastic astrocytoma survivor and therefore in the crosshairs of GBM. We have four beautiful children that also love and rely on their father, who is by all accounts among the best of men.

But we can’t will a cure into existence. In fact, throughout human history fraudsters have found that great promises and desperate fools such as myself make easy wins for them. Detached professionals tried to explain to me years ago why NWBO was a poor investment. It’s only in the last year that I’ve come to fully understand what they meant.

If now we’re relying on DC-Vax combo treatments, where does that leave the mono therapy trial?

Listing other possible signs of success doesn’t answer whether the combo trials are themselves such a sign. My point is that the combo trials are an ambiguous indicator.

In fact, most of the signs of success that eternal optimists are listing have some ambiguity in them. When you list them all together, they seem to support each other, but if you examine each one individually, none quite stands on its own. It’s a house of cards.

I’m sorry but it just doesn’t add up. I still have hope, but aggressive optimism could be quite dangerous to investors.

I have certainly run across that idea a lot — although, a few years ago the going estimate was that it was effective on a third of patients, then about 29 percent … now it’s 23 percent? It’s all just guessing unless the data are released.

Does this mean, Gary, that you do think the mono therapy trial has failed to show unambiguous improvement over the standard of care?

If we have to run dozens or even hundreds more combo trials to get an approved treatment, there might not be any improvements in my lifetime.

Maybe the best sign is that Ashkan Keyoumars in the UK is still working with DC-Vax, but is his optimism based on data or random luck? We need the trial results.

Anne

I am saying that maybe the combo trials are a good sign, but I always thought they could also be interpreted as the opposite of a good sign. Again, more ambiguity.

I was responding to posting that listed the combo trials as a sign of the success and imminent announcement of the mono trial.

Linda L. has been talking about a need for combo trials for years. But NWBO has been continuing the mono therapy trial throughout the same period.

The explicit and implicit messages from the company and message board cheerleaders have been that DC-Vax is expected to show enough of an advancement over previous treatments on its own to gain FDA approval as a mono therapy. The company even began a whole new series of trials of DC-Vax Direct on multiple difficult cancers.

The strategy was and is supposed to be to gain FDA approval for DC-Vax as a mono therapy added to or even possibly replacing the Stupp protocol. After approval it would be easy to combine it with other therapies for dramatic improvements. Instead now is UCLA moving on to all-combo trials?

Could it be a further sign that the trial that was data locked 19 months ago was a failure or, at best, ambiguous?

Use what as a control group? Did you mean to reply to a different post?

You seem to be agreeing with my original concern — that the combo trials may be a sign of loss of confidence in the mono therapy trial.

“There is nothing out that there that effectively addresses brain cancer “alone” and to bemoan the success of this treatment because it doesn’t work alone is mind numbingly silly, to be polite. **Your expectations have no basis in reality and that you would be disappointed by this product is quite frankly obnoxious.”

What’s with the hyperbole? Your logic is bosh so you’re insulting me instead.

The trial for which we’ve been waiting on for roughly a decade was set up to address brain cancer with DC-Vax alone. Through all that time and as recently as this minute there have been promises and affirmations that the treatment and trial are wildly successful, perhaps even the beginning of a cure for all cancers.

You’re saying it’s “obvious” to you that DC-Vax will never work on its own. Do you mean to say that the NWBO trial has indeed failed?

I really want to believe that these are all good signs, but are they?

The ASCO booth seems exciting, but their attendance at ASCO has been sporadic and unreliable. I don’t see why, if they have any good information, they would wait to release it.

As for the combo research, I’ve always thought that was a bad sign, a sign that DC-VAX is unreliable alone. They’re trying to pair it with something that’s also had wobbly results for a better outcome in combination.

The one thing Linda P. has been able to do reliably is to raise funds to pay herself and those close to her. She capitalizes on the irresistible idea of a cure for cancer. But that many people want the idea to be true doesn’t mean it is true. Many of us will overlook big flaws to protect the dream of keeping our loved ones safe. And Stupp’s connection most likely pays for itself in better fundraising power.

Data anomalies: It looks like someone doctored data in a brain tumor immunotherapy trial unrelated to NWBio:

https://retractionwatch.com/2021/12/21/researchers-devastated-after-finding-manipulated-data-in-study-of-pediatric-brain-tumors/

The paper was published in a Nature-branded journal and already cited 17 times. But a measurement had been selectively manipulated, and results couldn’t be replicated. They had to halt their plans for clinical trial.

Chilling.

[NWBO] “certainly aren’t obligated to ever release data under any enforceable laws so we may just legitimately never hear another mention of the trial.”

That really puts it in context, doesn’t it?

“The time from data lock to tld = mOS of glioblastoma.”

“…nwbo needs some experienced people to work smart…”

Exactly! The parable about the engineers who did in a quarter what their predecessors couldn’t do in a year is a perfect illustration of the potential that we’re missing out on simply because LP has all the control but no expertise.

Sounds good. Thanks for sharing!

“I’d be willing to almost guarantee … a win for NWBO and shareholders …”

That sounds familiar.

Who is dreaming up the cynical abstractions — holders of public shares who are entitled to information, or self-dealing c-suiters who hold as much information as close to their own chests as possible?

No one is questioning the idea of contracting in general. The question is whether it’s beneficial to shareholders to have the CEO of their company setting herself (and, possibly, unknown partners) up as the sole contractor upon which success of their investment depends. She pays herself, in the form of Toucan/Advent, with money from NWBio’s coffers. Is NWBio getting a good deal? If so, let’s see the books.

That other tycoons might set up similar self-dealing arrangements is no argument for their ethical standing or benefit to shareholders. They certainly benefit the negotiators. In this case “the negotiators” are principally one person.

Is the reasoning: NWBO wouldn’t want to get involved in the functions and costs of a manufacturing facility, therefore they hired a CDMO? But also: the CDMO can’t serve NWBO’s needs without high startup costs, therefore NWBO paid the costs anyway? And, by the way, NWBO and the CDMO are owned by the same person? Do the starry-eyed at-all-costs never-let-a-legit-doubt-go-unanswered bulls really not see anything at all potentially problematic here?

And the people with brain cancer? It isn’t only about the share price.

I am going back to all my college professors who said they would mark down late assignments because missing deadlines isn’t acceptable “in the real world.” I will tell them about NWBio.

Then again, maybe the professors were right and NWBio only belongs to the imaginary world, like cryptocurrency and Tesla Model S Plaid +.

Those are all good questions, H2R. I think the steady down-drift of the share price over the last several weeks reflects that questions such as those have continued to go unanswered. Perhaps this afternoon’s upturn will be more than a blip or a market-maker stepping in to bolster the price. Your guess is as good as any.

There are many little big dreamers invested in NWBO. If it weren’t for starry eyes (which I have too, and as well I am a teensy little investor), there would be much less tolerance for the lack of professionalism from the company’s managers.

Galois seems like a truly inspired character. I read only a little about him in a nice memoir-math book hybrid called Love and Math by Edward Frenkel. The book also touches on Russian social politics (especially with respect to Jewish mathematicians) making it somewhat timely. I highly recommend it. I still think about it often.

Today it is much more pleasant to discuss mathematicians and philosophers than Northwest Biotherapeutics. But fear not. For many months now, whenever the share price has dipped below $1.50 or $1.40, there has been some one or more who have stepped in to keep it propped up around the threshold.

But on which God should the wager be placed?

Covid testing is still going strong. Nearly 660,000 people were tested yesterday. “Only” about 17,000 tested positive.

The safety profile of DC-Vax appears to be great, but it’s relatively opaque in comparison with that of the covid vaccines. Millions of people have been vaccinated against Covid-19. Only hundreds have received DC-Vax, alas.

I’m sure you’re right, hankmanhub, but I’m not able to see it yet.

I don’t know where I put my notes, but when I sat down and calculated what outcomes would be necessary to separate the treated and untreated populations in a successful trial, the blinded data presented at least some potential for failure.

I think I worked the data a handful of different ways — separately calculating a 90 percent treatment arm at one extreme and 67 percent treatment at the other; and looking at the ranges across time for OS and PFS in comparison with assumptions provided by Smith on Stocks for typical placebo patients.

I don’t recall which numbers I used to represent expectations for placebo patients, but I think they were worse than the outcomes for the filtered Norwegian patients. So that would indicate a still achievable but more narrow path to success.

I still have hope, but other indicators seem to hint that this trial didn’t knock it out of the park. (But hey, if I turn out to be worrying for no reason I’ll have some consolation in the shares I have left.)

Has anyone else done similar calculations with the blinded data? If so, do you recall which assumptions you used for placebo patients?

Yes, I do hope it does demonstrate robustness in efficacy.

What I am concerned about is that the long tail of survival in the selected Norwegian patients is not terribly far off from the outcome of the same cohort in the blinded data in the DC-VAX trial.

On this board, it’s often said that the blinded data set is stellar and an obvious winner. But that appears to be by comparison to worse outcomes that are generally closer to the unfiltered Norwegian population. If comparison patients are thoroughly filtered as they were for the DC-VAX trial, the difference might be less certain.

Could the lack of an unambiguous separation have contributed to the decision to rework and resubmit the SAP to give themselves many potential paths to success?

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=162932554

Here is a link to the original post (above), from DCBAXX. A few people looked it over the first time around, but it bears further consideration. Forgive me if I pasted the link I correctly, but you should be able to find the relevant info, I hope.

Sometime last year or so, I went over a set of numbers compiled by Smith On Stocks, and I calculated my own estimate of the difference between NWBO and standard of care. The results weren’t as overwhelmingly awesome as I had expected them to be based on the posts I had been following on this board.

In fact, there is a small but nonzero chance, based on the blinded data and historical controls, that DC-VAX has little effect on overall survival, maybe even within the margin of error. The blinded data were inconclusive. That’s probably why they were published in a relatively minor publication.

That’s when I began to look at all the NWBO corporate communications with a more skeptical eye, and to really appreciate this board’s curmudgeons and Eeyores.

This Norwegian study appears to only make the outcome more uncertain.

I still believe DC-VAX has a shot. But it isn’t a home run, and the path isn’t entirely obvious, which is why they changed the statistical analysis plan and gave themselves a multitude of potential paths to success.

This study in Norway (link and citation below) might suggest that the many stringent selection criteria could be mostly responsible for the good-looking outcomes we saw for patients in the blinded-data NWBO paper.

Credit to a new poster (sorry — I forgot who) for bringing it to the board’s attention a couple months ago. The original poster also pointed out, crucially, that the data in this Norwegian paper extends 8 years, and the graphs extend accordingly.

https://academic.oup.com/noa/article/3/1/vdab008/6152004?login=true

Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: to whom do the results of the trials apply?

Erlend Skaga, Marthe Andrea Skretteberg, Tom Børge Johannesen, Petter Brandal, Einar O Vik-Mo, Eirik Helseth, Iver A Langmoen

Neuro-Oncology Advances, Volume 3, Issue 1, January-December 2021, vdab008, https://doi.org/10.1093/noajnl/vdab008
Published: 26 February 2021

A related question:

If they knew back in October (and presumably for years earlier) that it would take 8 months or more for their consulting experts to be ready to release top-line data, then why did they say it would be a matter of weeks?

If they didn't know how long it would take, why not? Do they have poor communication with their experts? Are their experts themselves unprepared or unaware of what needs to be done?

They have raised hundreds of millions dollars from faithful investors. Where has the cash gone? What kind of an operation is this?

Another completely hypothetical here: Is it possible they are sitting on failed or ambiguous results in order to keep the compassionate-use program going strong in the UK?

What part of the investment that NWBO has made in Advent is secured?

If the trial went well, I have hope that all will be made whole. But if the trial was an outright failure or ambiguous?

Sorry for not staying up to date with the board postings, but what’s the evidence that they’re working on journal article? I thought it was only a supposition.

Thank you, Karlchen. Your creativity is appreciated. Well done.

Did they make false promises, or merely imply them?

I am genuinely asking. I don’t know the answer. But I wouldn’t be surprised if it were the latter, as they’ve done so in previous years. They are extremely cautious lawyers, careful to follow the letter of the law, if not the spirit of it.

This is encouraging. Thank you for sharing.

Thank you!

It’s nice see LL out and about advocating for her views even if there doesn’t appear to be anything new here. She has long argued that there is a need for a different approach to clinical trials for GBM for the reasons laid out in these slides. It still comes down to the judgment of the regulatory bodies. We’ll know when we know, apparently.