Replies to post #771414 on NorthWest Biotherapeutics Inc (NWBO)

[learningcurve2020]

All that and the company’s running on fumes with a Going Concern warning and no independent CFO.🤷‍♀️

[eagle8]

Great job TDD (also d_stock).
This looks fantastic!
What a combination of DCvax and Roswell!
Huge time savings and therefore faster treatment options.
My thanks to you is great, also for this pdf!
When I just think about interleukin-7 + DCvax Direct, a lightning fast effective treatment for the Tumor and also a killer for the competition.

I hope you don't mind me posting your X posts here often.
I know you can only post 1 post per day, so.


Best to you.

[Galzus Research]

The major problem with dealing with misinformation associated with AI-generated content is the speed at which it can generate complete garbage.

Patents

Do not matter if your drug never gets approved (aDC1).

[DCVax] is highly effective in primary tumors like glioblastoma, especially post-surgery.

We actually don't have that evidence. There was an OS benefit shown in the phase 3 trial, yes, but just like in the Provenge pivotal study, no benefit in terms of objective response or progression-free survival was demonstrated. This does not preclude activity, but there is insufficient evidence to support this claim.

To pre-empt the inevitable "but how did they get an OS benefit, then?" Answer to that is...there might not be one. They did not complete the study as a randomized trial, so the door remains open to the fact that the OS benefit is not real.

Regulators required the gold standard: Overall Survival (OS) as the endpoint.

Then how were they able to start the study with PFS as the primary endpoint?

This meant a long, expensive trial with extended follow-up.

In GBM, this does not need to be the case. EF14 enrolled twice as many patients, started in 2009, and had a readout for OS in 2014. The ACT IV trial also enrolled over 700 patients, initiated in 2011, and had its readout in 2017.

It does not need to take 20 years from start to finish. Not even 10.

[Factual errors using AI]

Objective response rate is not just the measure of tumor shrinkage. It is the rate at which patients who have measurable disease experience shrinkage of their primary measurable lesion beyond 35%. Shrinkage below that threshold does not count as a response.

And progression-free survival is not "how long the disease is stabilized." It is the time until the patient 1) dies, 2) has disease progression (either new lesions or growth beyond a predefined threshold of the measured lesion).

So, stepping aside from the technical errors in your AI-generated writeup, the fundamental issue with using these surrogate endpoints is whether they're meaningful. NWBO loyalists have chanted "pseuodoprogression, pseudoprogression, pseudoprogression" as the reason for the switch away from PFS in the first place, taking at its face that the action of these dendritic cell vaccines cannot be distinguished from tumor progression.

Has that gone away or something? If pseudoprogression is not actually a problem, then we should be able to honestly discuss DCVax-L's activity in the phase 3 trial (ie, the lack of evidence for it). If pseudoprogression remains a problem, then you're not going to see objective responses from DC vaccination, and therefore you're not going to get a reliable measure of ORR or PFS to facilitate your rapid approval.

That's the key thing about these surrogate endpoints: you have to demonstrate compelling evidence that the endpoint is being met, and you also need to have a firm rationale as to how that makes a meaningful impact on patients.

These trials already use ORR and immunologic biomarkers as primary endpoints. The regulatory strategy is already underway, and NWBO inherits the full commercial rights.

They're phase 2 trials. OF COURSE they use endpoints of initial activity and then correlates. These are hypothesis-generating studies, not 4D chess moves.

In March 2024, a peer-reviewed study published in Nature Communications demonstrated a significant breakthrough in the use of early gene expression signatures to predict long-term survival in glioblastoma patients treated with dendritic cell vaccines.

Absolutely meaningless right now beyond being a neat piece of science kit. To be of any relevance in clinic, physicians are going to demand that the information be actionable in some way. Either it needs to inform what treatment approach to take (ie, a molecular marker that tells you what targeted therapy to prescribe), whether the patient needs to move on to something else, or whether a treatment option should be excluded altogether.

This gene expression profiling, by definition collected after treatment has begun, provides no useful information. You wouldn't stop giving the DC vaccine based on the findings. You wouldn't add something else on to salvage (for multiple reasons). You wouldn't be able to go back in time and pick a different treatment approach. This biomarker is completely useless for clinicians. Possibly useful to generate new hypotheses, but absolutely not useful for moving toward approval.

If such biomarkers are validated, they can serve as surrogate endpoints in regulatory filings

Huge, huge "if" there. You do not have the first clue what goes into validating these types of biomarkers to the extent that they would be usefully applied toward FDA approval.

More well-defined biomarkers (think path CR, ctDNA elimination) are available right now, and they do not serve as useful to the FDA in terms of approval decisions. There is one example where pCR led to an accelerated approval that I could find, and that was in breast cancer, where pCR is arguably at its most well defined and trusted as an endpoint.

Regulators such as EMA and FDA increasingly accept surrogate biomarkers when they are “reasonably likely to predict clinical benefit.”

Your definition of "reasonably likely" is highly unlikely to align with what the regulators are talking about here.

[JTORENCE]

So when is this supposedly game changing presentation taking place??

[dennisdave]

Dr. Marnix Bosch is going to be speaking about next generation dendritic cells (aDC1, alpha-type 1 polarized dendritic cells) on Monday.

sure lets talk about the next gen DC's while the first generation is still not approved. Classic