OncoSec Medical Inc (ONCSQ)

[hschlauch]

past data indicated that this trial would be a roaring success, with a ceiling for the response rate appearing to be 40%, which would be spectacular in this population.

The earlier phase 2 trial's (OMS-I102) data reflected a predicted non-responder population, a fraction of whom failed prior anti-pd-1 therapy. Out of the patients who were truly refractory to anti-pd-1 therapies - I think 10 individuals were reported who fit this category - 2 of them actually responded to the TAVO plus pembrolizumab combination. In other words 20% anti-pd-1 nonresponders responded on the TAVO plus pembrolizumab combo, not 40%.

These are somewhat different patient populations (OMS-I102 vs. PISCES). Oncosec and others on this board (and now Mr. Hartman) obfuscate the statistics from the OMS-I102 trial. This is doing all of us a disservice. The BORR reported by Oncosec for OMS-I102 included patients who were on various prior therapies, not just anti-pd-1. Some of these patients failed on anti-ctla-4 monotherapy, for example, and not on anti-pd-1.

The assay that was used to qualify patients in the OMS-I102 trial was percentage of exhausted CD8 T cells (TIL). They had to be below 25%. Unfortunately, the vast majority of patients who are refractory to anti-pd-1 therapy tend to have very few or no detectable exhausted CD8 T cells present, well below that 25% threshold. The PISCES trial appears to have enrolled patients who are immunologically very cold and possibly well below that 25% cutoff that was selected for the OMS-I102 trial.

While I was hoping the enrolled patients in PISCES weren't so immunologically frozen, it appears that may have been the case for most of the individuals reported in the preliminary analysis. Is this an accurate representation of all refractory anti-pd-1 patients with advanced melanoma? I don't believe so, and I think expanding the trial size will illuminate that fact. The TAVO plus pembrolizumab combination is indeed rescuing some of these patients who are failing anti-pd-1 treatments, but it isn't yet clear what baseline characteristics are necessary to get responses with TAVO plus pembrolizumab. Do the nonresponders have relatively higher concentrations of Tregs, not just intratumorally, but also in tumor draining lymph nodes? Is the CTLA-4 on the Tregs hijacking antigen presentation, thus preventing priming?

If 10% is indeed clinically meaningful for this patient population, then what Oncosec is currently achieving in refractory anti-pd-1 patients is certainly worth monitoring in my opinion.