OncoSec Medical Inc (ONCSQ)

[hschlauch]

Oncosec's PISCES trial is enrolling patients who have failed prior checkpoint inhibitor therapy, ie anti-PD-1, in stage III/IV melanoma. Patients who were enrolled in the P2b trial - combination pembrolizumab and Immunopulse IL-12 - weren't treatment naive, and the majority of them failed prior checkpoint inhibitor therapy. And these patients were selected because they had such low percentages of a partially exhausted CTL phenotype - they could have selected predicted nonresponders or actual nonresponders with higher percentages of the exhausted phenotype, a marker of CD8 T cell activation, but nope, they didn't go that route. These were patients with very few CTL. These types of patients have very limited options once they fail anti-PD-1 therapies.

So what is stopping them from achieving better results in the P2b trial? Well, we can start with describing the patient population - again, not treatment naive patients and not just any predicted nonresponders, but patients who have essentially little to no activated T cells at baseline! Also, based on spatial analyses of the tumor microenvironment, the P2b nonresponders to the combination had much higher quantities of intratumoral FOXP3 Tregs in close proximity to CD8 T cells; this suggests to me that those Tregs, which might also be expressing CTLA-4, are preventing T cell activation by outcompeting CD28 for ligands on dendritic cells.

So, adding an additional encoded protein to a plasmid that just abates Treg-induced immune suppression, would theoretically lead to improvements in T cell activation. And improvements in T cell activation then drives the percentage of partially exhausted CTL phenotype, which are - in addition to PD-(L)1 on tumor cells - a prerequisite for anti-PD-1 responses.