Replies to post #36392 on OncoSec Medical Inc (ONCSQ)

[goodJohnhunting]

Greetings hschlaunch,

Here is something else I just noticed in the immune profiling for PPHM's preclinical data presented at this year's AACR (I think this is what sets EP IL-12 apart from Bavi and other IO agents):

First and most importantly, the mouse equivalent Bavi does not demonstrate an inflamed immune profile. You will note that macrophages, Th1 cells, total tcells, DC cells, PD-1 positive tcells, and interferon gamma do not change much if at all after administration with Bavi.

So what is Bavi's MOA in my opinion? It is capable of reducing immune suppressing cytokines. While this benefits responses, I don't think it is going to add much long term survival benefit over anti-pd-1 agents used alone or in combination with an anti-CTLA-4 agent.

In short, I don't think Bavi is actually improving immunity and driving more TIL, it is simply reducing the number of suppressor cells.

I've had the same argument over on the PPHM.

History has shown (mouse studies, preclinical, clinical) very little adverse immune reaction to Bavituximab, such has been seen with most Monotherapeutic MaBs (Provenge, Yervoy, Keytruda, etc)

The defense has been, Bavituximab eliciting an upstream response, and reduction in IL10 and an increase in IL12 within the tumor mircoenvironment, thus allowing immature dendritic cells to mature into tumor specific APC's..

This theory has holes, and I've had the argument many times over there.

I'm super interested in EP-IL12. It seems logical and scientifically plausible. Not to mention, some what easy to understand.

All the best,
John

[hschlauch]

Just a little more refinement...

Reducing suppressor cells in combination with an anti-pd-1 agent is synergistic to a degree. In fact, I have read and heard that anti-CTLA-4 agents harbor the same MOA, i.e. they don't actually improve the number of TIL, but they reduce the number of suppressor cells.

Therefore, I think Bavi would be akin to using an anti-CTLA-4 agent with an anti-pd-1. If true, efficacy and safety with a Bavi and anti-pd-1 or anti-pdl1 combination should look similar to an anti-pd1 and anti-CTLA-4 combination. Mixing all three together though would not only be very expensive, but would theoretically be very toxic with negligible added benefit.