OncoSec Medical Inc (ONCSQ)

[hschlauch]

The Epac plus Keytruda failure was predictable. There won't be much improvement in PFS or OS with Epac if it is being used with an anti-PD-1 agent alone. The problem is timing: patients need to have a preexisting immune response at baseline in order for these agents to work well, and neither one of the two drugs primes anything.

Here is what I had previously discussed regarding IDO inhibitors:

My interpretation of the immunosuppressive factors (i.e. depletion of tryptophan) associated with IDO1 is that the enzyme becomes upregulated in the presence of interferon gamma - your articles also support this notion. There appears to be a very strong positive correlation between IDO1 enzyme production and interferon gamma levels. This is also true of PD-L1 upregulation on tumor cells and dendritic cells in the presence of interferon gamma. If indeed interferon gamma is driving the upregulation, then it stands to reason that there needs to be a pre-existing immune response present prior to administration of an IDO1 inhibitor. The same is true for anti-PD-1 and anti-PD-L1 checkpoint inhibitors as well - they simply won't work if there is no pre-existing immune infiltrate and upregulation on tumor cells

Priming needs to occur intratumorally and/or in tumor draining lymph nodes.