OncoSec Medical Inc (ONCSQ)

[dangerM]

~ If the company has already committed to a IL-12 + Flt3L combo and why it has been so quiet:

I don't know if it'll make a difference, but I wrote a mail to the company about my observations and my opinion why a multi-gene / combo product (suspectedly with Flt3L) will be a must. I also slightly wondered about the function / addition of a TLR3 in such a combo (the trial I referenced to several months ago used a Flt3L with TLR3 and SBRT).

Perhaps one reason to stay "under the radar" could be to gain a headstart relative to competitors. See the many, many anti-PD-(L)1 mAbs in clinical trials. IMHO they aren't a real danger for the anti-PD-(L)1's currently on the market. There might be a competition between the big pharma companies (pembro vs. nivo. vs. avelumab ...) ... but as soon as "all" the combination studies have played out, IMHO the development of a new anti-PD-(L)1 will be too expensive or simply not efficient relative to other targets, since a new anti-PD-(L)1 will have to do all the combination studies to be approved in each of these settings.

I've been re-reviewing the available data from Oncosec's trials to better understand why some patients are responding to EP pIL-12 in combination with anti-pd-1 agents and others are not.

I think I am much less qualified than you to give an answer. So what follows are rather random thoughts, plus a bit biased, since I've been reading somewhat focussed on metabolic changes in the TME recently.

What I'll be looking for in a publication about OMS-102 will be some insight into size of treated lesions and response. This is highly speculative, but I'd suspect one should definitely not leave out treating the small lesions; IMHO they are not only easier to "finish off" (there is some interesting biomarker mouse data about small lesions fully vanishing within 7 days on some old poster); but as well, I'd expect memory cells generated there to migrate to and expand at other, larger lesions.

Not only for Oncosec, but generally, very large tumor masses are more difficult to cure. They are a hypoxic, low glucose environment, some with a necrotic core. Immune cells (both Teff and Treg) in such a TME seem to switch to a different type of glucose and then even fatty acid metabolism instead which creates more ROS ("reactive oxidative species", not to be confused with ROS1) and ultimately show mitochondrial damages/impairment. Somewhere I read that Treg are even more affected by this than Teff (and this is no help since even dead Treg are really surprisingly immunosuppressive https://www.nature.com/articles/ni.3868 - another reason not to kill the Treg but convert them/avoid that they are generated in the first place).

So I hope there'll be some spectrum of different lesion sizes / tumor masses in Pisces with hopefully not too many large ones.

Well, let's see ...