Replies to post #539317 on NorthWest Biotherapeutics Inc (NWBO)

[biosectinvestor]

Dr. Liau's 2021 comment is after that trial was said to be over. I know because it was discussed when we anticipated that trial and we knew it had been canceled and speculation was that MRK offered a better deal when we saw the MRK deal materialize. Many then concluded that BMY must have been sidelined by a better offer from MRK to do more to make it happen. It is also possible that they wanted to proceed with just a DCVax-L and Checkpoint inhibitor trial first, then add the CSF-1Ri as a next stage trial and BMY was ready for that trial. Hard to know. Also, it may be that that next trial will proceed with MRK instead, or any of a number of other Checkpoint Inhibitor providers. You never know. At the time of the drafting of the latest description of the SPORE grant, it indicates MRK may have been taught to be the expected sponsor of that trial. As to whether Dr. Liau's words or the draft of that document is determinative, obviously I have no idea. They want DCVax-L, a checkpoint inhibitor and a CSF-1Ri drug together and they see it as extending survival.

I posted that earlier in response to the initial question, my initial skepticism re the BMY trial that ATL had mentioned because of the video. What we do know is that they appear anxious to add CSF-1Ri to the mix, and Dr. Liau gave numbers lectures this summer where the issues that would call for CSF-1Ri were repeatedly mentioned. Specifically an additional layer of cells that cause immune suppression after the checkpoint inhibitors have done their work,

https://trp.cancer.gov/spores/abstracts/ucla_brain.htm

We previously found that, in addition to inducing T-cell infiltration into brain tumors, DC vaccination + anti-PD1 blockade may also create a pro-inflammatory environment within the tumor that induces the immigration of immunosuppressive myeloid cells (TIM). TIM are phenotypically similar to the myeloid cells that attenuate the T-cell response to chronic viral infections, and may counteract the anti-tumor T-cell responses induced by DC vaccination. Therapies that target myeloid cells within the tumor microenvironment represent a promising new strategy. As such, inhibition of these myeloid cells using a CSF-1R inhibitor, in conjunction with autologous tumor lysate-pulsed DC vaccination (ATL-DC) and PD-1 mAb blockade, resulted in significantly prolonged survival in tumor-bearing animals with large, well-established intracranial gliomas. Our hypothesis is that myeloid cells mediate adaptive immune resistance in response to T-cell activation induced by immunotherapy. We have planned a series of novel pre-clinical studies to re-polarize myeloid cells, to optimize how the timing and sequence of immunotherapy can influence ant-tumor immunity, and a new clinical trial to test the first-in-human combination of a new brain penetrant CSF-1R inhibitor (CSF-1Ri; PLX3397, Daiichi-Sankyo) with DC vaccination and PD-1 mAb blockade (Pembrolizumab, Merck) in patients with newly diagnosed GBM. A better understanding of the biology of these cellular interactions will provide insight into more effective ways to induce therapeutic anti-tumor immune responses for this deadly type of brain tumor.

Upon further due diligence and research including my review of the SPORE grant, which was refreshed just a short time ago, that trial is clearly something anticipated yet to occur.

It is also outlined on the UCLA website as a promising area but then only animal research, including the use of of the PLX / CSF-1Ri drug. It's then also referenced in the combination patent filing.

As I said, it is a road map.

And this is an image from this summer's presentations below, slide 27:



https://virtualtrials.org/dcvax/dcvax.pdf

And again, for a fuller discussion of CSF-1Ri, here: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=170546683