ZIOP - ahead of the CAR pack - they already have a CAR +IL15 (armored car) and will incorporate the PD1 along with a non-viral modality (sleeping beauty) and modulating it thru use of RTS switch. Its worth an investment in my opinion.
Musings on Cooper 12/16, Cytokines making the PD1 inhibitor work, IL 12, why ZIOP wins in the end
My takeaways from Cooper’s 12/16
1) 4 necessaries for a T Cell
And when a T-cell is fully activated, 1. it kills and it re-kills, 2. it proliferates, 3. it makes cytokines, 4. and it protects itself from undergoing apoptosis. If you want to generate a T-cell that has all of those four attributes, you have to not only signal through the CAR but you have to signal through the cytokine receptor, the common gamma cytokine receptor, and we’ve done that. And again, the data on the bottom right shows you the preclinical modeling with a molecule that we are developing, known as membrane-bound IL-15, that is essentially co-expressed with the CAR and it will give long-lived, essentially proliferative potential to these T-cells.
2) Make T Cells immune to cancer cell’s blocking with Programmed Death 1
It is our intent though, as a combined organization, not to just bring forward another CAR or another TCR. There are many people doing that. What we want to do is focus on the marrying of the next generation CAR or TCR with finite biology that really helps to define and determine that optimized cell approach, be it a T-cell or an NK cell. To this end, we are looking at various technologies to allow us, for instance, to modulate to PD-1. I’m sure that you are familiar with Opdivo and KEYTRUDA as well as Yervoy. These are blockbuster drugs that are revolutionizing the space for a number of different malignancies including lung, head and neck, gastric, bladder, just to mention a few. Well, for us, it’s possible to take away the needs for the systemic administration, by inclusion into the T-cell, a modality to regulate the levels of those molecules on the surface. We believe that this is important, because it helps to define a very active T-cell and helps to define a very interesting biology, whereby we can actually modulate that T-cell’s functionality.
3) Why Ziopharm will win the race in the end
So I understood this is the very beginning of the story, and we will win because, A, we’ll keep the cost down; and B, we are already developing multi-modality therapies just as I have ticked off the box a few seconds ago. And we’re going to be able to do so in an organized way and using fundamentally a programming language, a language built around non-viral gene transfer and a language built around the switch technology so that we can control all of these effector cells.
