Replies to post #296899 on NorthWest Biotherapeutics Inc (NWBO)

[anders2211]

seems to me you moved your target of interest to Direct and you kinda starting to accept that L will have an enormous chance of getting approval.

Doesn't mean that you are not right on Direct. The fairytale store of easy approval for D after approval of L and both being almost the same irritated the hell out of me and was as much misinformation being spread as some of the nonsense stories shorts/disbelievers are/were spreading.

[beartrap12]

Ex, Direct is injected directly into the tumor where the tumor is used in vitro. So, both L and Direct use the tumor.

Optune is a very, very bad example to use. Even Dr. Liau questioned their numbers for rGBM. No wonder it took years to get nGBM. The helmet may work on paper, but not in the real world, IMO and Dr. Liau’s opinion.

Anyway, I’m just discussing what was said by a brain surgeon and/or an Expert doctor of immunotherapy. You’re welcome to your opinion. I’ll stick with the experts.

Yes, we don’t know if FDA and other regulators will go for the argument that the two products are the same, but we’ll enjoy discussing it while we wait for results.

[biosectinvestor]

Your passion suggests otherwise.

Direct has no antigens. You said it. So it is the patients own blood components injected after some fairly minor processing, and I would bet the processing is virtually the same as L, except no antigens... no exposure to a tumor externally.

I’m not suggesting they will be approved at the same time, but the notion that they are easily considered a single platform, ultimately, I think will drive shorts insane trying to suggest otherwise.

And I do not see that there is a great case for that point. On the other hand, approvals and labels can be somewhat bureaucratic and have been in the past, but I also think the entire thought process related to cancer is being transformed by immune therapies. I note you’re pointing to examples that are not immunotherapies. You might’ve pointed to Keytruda, which is one of the first such broad approvals based upon biomarkers. That process makes more sense than approvals based upon location or whether a tumor is operable or inoperable.

I think you just don’t want to hear the idea, so you’re going to resist it. That’s fine. That’s just a legacy/old way of thinking. Just don’t invest on that basis, IMHO, that things will always be the same. They won’t be.

20th Century Cures Act! Love it!

[skitahoe]

While I agree with you that label expansion takes a major effort, I also believe that in the interim off label use grows, and that the major cancer hospitals and oncologists know how to get insurance coverage for the use of major drugs off label for most patients.

I know that I've been on drugs that never were put through trials for my specific form of leukemia, yet I believe they're accepted practically everywhere for it's use. I doubt that trials will ever be run because the medical community has simply accepted them without such a trial.

I don't know that will happen here, and if so, how quickly, but I do believe there is already some anecdotal evidence of efficacy in other cancers. In some cases the drug maker may be willing to provide a drug for someone with a different form of cancer at no cost to learn it's benefit, in others people with the funds to pay will try anything their Doctors suggest if it will potentially improve their outcome. My point is that anecdotal evidence will build of efficacy in certain cancers, in time insurance will go along, and it will be up to the company whether to go to the expense of trials, or simply allow the product growth to occur based on growing anecdotal evidence, and insurance acceptance of its use. If the insurance company sees an improved outcome it may also see a lower cost overall, if that's the case, it's a no brainer.

Of the leukemia drugs I've been on, none are cheap, some are available as generics, but have list prices close to the original. While the insurance company may have preferred my Doctors selecting the cheaper drug, at no time did they argue with the selection of my Dr. at City of Hope. While this might not always be the case, I believe that most Oncologists can get the drug of their choice if they're willing to fight for it. I never know what's actually paid, my co-pay isn't that different if I'm getting something that's available as a generic, or not. The key is, either way, it's a tiny fraction of the list price, and I don't believe anyone other than the insurance company and drug maker know the price that's actually being paid.

Gary

[tshell01]

Your examples are fish oil and a helmet? Yeah I can imagine those being long term desperation processes...

[longfellow95]

I would say they are similar in principle. Use the maturational cocktail to optimally mature the dendritic cell pre-cursors that come from the PBMC's from the leukapheresis.
Though this is more time critical with Direct so that you derive 'adolescent' dendritic cells, that have both migratory capacity to lymph nodes and also antigen presenting abilities.
And it's incorrect to say that Direct 'uses none' of the tumor antigens. It uses all of them, at least theoretically.
It's just that with L the antigen presentation is in vitro and with Direct it is in in vivo. But the fundamental principle is the same.
There is no guarantee that they will have equivalent efficacy.
Direct may elicit a lower response rate than L, or it might actually be better. Who knows?

Direct manufacturing is simpler due to only having the one autologous component and not two, and that is probably why Direct is more amenable to closed system automated manufacture. Which will likely make it cheaper to produce, and possibly a cheaper therapy.
I think everything is more time critical with Direct, because the intention will always be to administer it asap after manufacture.

There is a detailed paper floating around somewhere that came out of the Direct P1, which went into quite a lot of detail about how they had learned the time critical partial maturation, which they had previously referred to as Method B (for better).
And I remember thinking that they were in danger of giving their secrets away in that paper, because it was so detailed.
But I've lost the bookmark somehow.
Don't know if anyone knows the one I'm talking about, and can perhaps put up the link.

It's somewhat moot as to what extent an approved L could be used off-label. I don't see why it couldn't be used in other cancers wherever there is a tumor resection, if the responsible physician believes its use is justified. Though that might be pushing off-label discretion a bit far.
For sure, I think it could be used off-label for any type of resectioned brain tumor, not just GBM.

Yes the first Direct P3 would take a while, and you would come straight up against a single-arm versus a randomised study dilemma.
Randomised would bring up all the ethical issues of denying a control a potentially life-saving treatment, and injecting a tumor with a placebo??
But with a single arm, how do you get a control comparison?
So trial design would be critical to ensure that you get a speedy outcome that gives you data that warrants approval. Would Direct be granted the same smooth passage as the Car-T single arm studies? I very much doubt it.
I loathe tumor response rate as a surrogate for OS, but if they wanted AA through interim analysis, that is probably what they would think of using.

Think you're being too negative about this. If L is approved everything else should follow, if a level playing field exists.
The resistance and obstacles would come from the status quo, that would recognise Direct as a big challenge to the established order in cancer treatment.

Just opinion.

[Doc logic]

exwannabe,

L and Direct represent different stages of maturation/activation. Prefab housing or all built on site doesn't change the way the house looks when it's finished being constructed. The maturation process is mostly complete with L which gives it immediate mobility towards the lymph zone. With Direct it is left incomplete to be able to pick up the antigens in the tumor where it becomes mature to the point of mobility to the lymph zone. Best wishes.