NorthWest Biotherapeutics Inc (NWBO)

[biosectinvestor]

You're apparently not following the evolution of the regulations with regards to extending indications and getting coverage for other indications based on real world evidence, for drugs once they are approved for one indication.

They are clearly collecting the kind of biomarker evidence that they will need over time to extend to other indications.

This is just one example, but on the other trials the combinations and others, trial managers have clearly also collected biomarker data.

https://nwbio.com/wp-content/uploads/NWBT_ASCO_slides_06032023_FINAL.pdf

https://nwbio.com/video-dr-marnix-bosch-speaks-at-asco-2023/

Combination Trial:
https://classic.clinicaltrials.gov/ct2/show/NCT04201873

Primary Outcome Measures :
Cell cycle-related signature [ Time Frame: Up to 6 years ]
Expansion of T cell receptor (TCR) clones [ Time Frame: Up to 6 years ]
Two-sample T-test with Bonferroni adjustment will be used to compare the increase number of expanded TCR clones after dendritic cell (DC) vaccination with PD-1 blockade in Group A versus (vs) DC vaccination with a placebo in Group B.

Incidence of adverse events (AEs) [ Time Frame: Up to 30 days post treatment ]
Adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. All patients who receive any amount of pembrolizumab/placebo or ATL-DC vaccination will be evaluable for toxicity, serious adverse events (SAEs), and events of clinical interest (ECIs).


Secondary Outcome Measures :
6 month progression-free survival (PFS6) [ Time Frame: At 6 months ]
Efficacy will be measured by percent PFS6 as defined by Response Assessment in Neuro-Oncology (RANO) criteria. Kaplan-Meier (KM) curves and median estimates from the KM curves will be provided as appropriate. Percent PFS6 will be estimated from the KM curves and compared to historical controls.

Overall survival (OS) [ Time Frame: Up to 6 years ]
OS will be compared using log rank test.


Other Outcome Measures:
Biomarker analysis [ Time Frame: Up to 6 years ]
The association between biomarkers and clinical outcomes (PFS and OS) will be evaluated using Cox regression. Changes in markers pre- and post- treatment will be assessed using paired t-tests.

TIL (tumor infiltrating lymphocyte) density and TCR (T cell receptor) Clonality in the tumor quantitatively measured by next generation TCR sequencing [ Time Frame: from baseline to surgery ]
The differences of TIL density and TCR Clonality between the archival tumor (pre-treatment) and protocol tumor (post-neoadjuvant treatment) will be assessed using paired T-test, and the association between the changes in TIL density and TCR Clonality and clinical outcome (PFS and OS) will be evaluated using Cox regression.

TIL density and TCR Clonality in the peripheral blood quantitatively measured by next generation TCR sequencing [ Time Frame: from baseline to surgery and post surgery treatment period, up to 24 months ]
The changes of TIL density and TCR Clonality in the peripheral blood from samples collected prior to neoadjuvant treatment and samples collected post-neoadjuvant treatment at each MRI visit will be assessed using paired T-test, and the association between the changes in TIL density and TCR Clonality and clinical outcome (PFS and OS) will be evaluated using Cox regression.

gene expression signature and somatic mutations in the tumor measured by RNA Seq and nano string IO360 [ Time Frame: from baseline to surgery ]
The differences of gene expression signature and somatic mutations between the archival tumor (collected pre-treatment) and protocol tumor (collected post-neoadjuvant treatment) will be assessed using paired T-test, and the association between the changes in the cell cycle related gene expression signature and clinical outcome (PFS and OS) will be evaluated using Cox regression.

gene expression signature from peripheral blood measured by RNA seq and nano string IO360 [ Time Frame: from baseline to surgery and post surgery treatment period, up to 24 months ]
The changes of gene expression signature in the peripheral blood from samples collected prior to neoadjuvant treatment and samples collected post-neoadjuvant treatment at each MRI visit will be assessed using paired T-test, and the association between the changes in gene expression signature and clinical outcome (PFS and OS) will be evaluated using Cox regression.

T cell subset and activation markers within peripheral blood measured by flow cytometry [ Time Frame: from baseline to surgery and post surgery treatment period, up to 24 months ]
The changes of T cell subset and activation markers in the peripheral blood from samples collected prior to neoadjuvant treatment and samples collected post-neoadjuvant treatment at each MRI visit will be assessed using paired T-test, and the association between the changes in T cell subset/activation markers and clinical outcome (PFS and OS) will be evaluated using Cox regression.

TIL quantification including tumor quantification of PD-1, PD-L1, CD3, CD4, CD8, Iba-I, Ki-67 measured by immunohistochemistry of FFPE tissue [ Time Frame: from baseline to surgery ]
The differences of PD-1, PD-L1, CD3, CD4, CD8, Iba-I, Ki-67 protein expression level between the archival tumor (collected pre-treatment) and protocol tumor (collected post-neoadjuvant treatment) will be assessed using paired T-test, and the association between the changes in the protein expression level and clinical outcome (PFS and OS) will be evaluated using Cox regression.

NWBO has a platform treatment that has demonstrated potential for other indications, broadly. They will, in my opinion get approved for GBM. I expect that other trials will allow them to extend to gliomas and that they will likely also see potential for getting the indications extended for many other cancers.

No, they won't have to do a trial for every extension (this is why the 21st Century Cures Act was so important, providing earlier access to new drugs without the rigamarole that delays access for many years), I believe, given the new regulations. But a trial will help to prove efficacy for specific indications.

Given the low side-effects, ease of administration and apparent method of action as well as demonstrated results for some patients, I think it will be very likely that doctors will consider DCVax-L to be a very viable potential treatment for many solid tumor patients, whether on initial occurrence, or recurrence of their tumors.

I doubt the company will get bought out immediately because I do not think, as you point out, that they will immediately get credit for their full potential. That might not be for many years. But I do think if they wait it out, they will find themselves deluged with opportunities to do combination therapy demonstration trials with various other Big Pharma drugs, some of which that perhaps wish to have a major indication where they can outshine, let's say, a Keytruda. This by itself might drive a bidding war ultimately to buy NWBO.

I'm looking forward to it.