Synergistic Activity of NKTR-214 With Nivolumab

Adi Diab, MD:NKTR-214, as I said, is a cytokine that leads to proliferation of the T cells and infiltration of the T cells into the tumor microenvironment. And proliferation is considered the first needed step for an active immune response. Whether it’s against cancer or against infections, proliferation is considered the hallmark of an active immune response. Once you proliferate, you also get the T cells activated and you get an activation marker. PD-1 is one of the activation markers. Obviously, it’s engagement whether its ligand, the PD-L1, lead to the exhaustion. But as a phenotype T cell that has PD-1 on the surface, it’s a marker of activation.

And we notice from the monotherapy trial, from the on-treatment biopsies that we obtained in the patients who received NKTR-214, that the infiltrating T cells into the tumor microenvironment across different cohorts of tumors notice them; they’re upregulating their PD-1. And that has led us to, and supports, the rationale that combining it with anti—PD-1 agent will be very helpful. Obviously, the preclinical data also supported the combination and demonstrated the synergy.

But furthermore, these are completely nonoverlapping mechanisms. One truly lead to the stimulation of the immune cells. And sometimes you can call it a nonspecific way, anti—PD-1 rescue, most likely specific T cells that recognize the antigens. So, it relies on the immune system to recognize the cancer and then it comes to play by rescuing the last step of inhibitions but not necessarily contributing to the increasing of those T cells that recognize further antigens.

We believe that NKTR-214, based on the preclinical data, allow for enhancement of T-cell recognitions into the tumor microenvironment. And it brings more T cells into the tumor microenvironment. And these, as we continue dosing the NKTR-214, continue to bring more infiltration into the tumor microenvironment. And that’s the hypothetical mechanism that suggests that there might be synergy between those 2 agents.

Transcript edited for clarity.