Replies to post #41541 on OncoSec Medical Inc (ONCSQ)

[daskapital_]

hschlauch:

Thanks for your resourceful interpretation as always, especially the comparison of toxicity between IMO-2125 and IL-12 and the mentioning of the Dynavax trial. I have a major concern and a minor one on which I wish that you can provide some info and insight.

As for the minor one, I check the results for IMO-2125. They stated that there are 5 CR or PR out of 10, but did not specify on the respective numbers of CR or PR. So based on what you claim that "50% overall response rate and 0% complete responses"?

As for the major one, I think the haunting question is still the criterion for identifying anti-PD-1 non-responders. In the current trial, Oncs uses two biomarker assays, rather than patients who actually failed checkpoint inhibitors. This identification approach, according to your previous posts, "select the worst of the worst" and is stricter than selecting actual checkpoint progressors. You addressed the scientific reasoning in a earlier post about the "exhausted T cells" and argued that the biomarker assays have a very strong predictive power for non-responders.

Now according to Oncs, "subset of patients previously treated with checkpoint inhibitors demonstrate 33% BORR (9/22 as the subset, 3/9, 2PR 1CR)". Meanwhile, the full set achieves a 50% BORR (11/22, 2PR 9CR), which is higher than that of the subset. If your theory is correct, should not we expect to see a higher BORR in this subset of patients than the full set, since their immu-conditions are somewhat better than the average level of the full set? What might be the problem here?

This also seems to be the concern expressed in AF's earlier and recent pieces about Oncs. He seems to be insisting that the criterion defined by actual checkpoint progressors. On the other hand, the trial for IMO-2125 only recruits actual checkpoint progressors.

Hopefully we will get more info on this criterion issue tomorrow and as PISCES, which only recruits actual checkpoint progressors, unfolds.

Highly appreciate your scientific input. Many thanks!

[daskapital_]

Correction:

This actual-checkpoint-progressor subset does not necessarily have better immu-conditions than the average level of the full set, since they also fail the biomarker assays. But as long as it is somewhat representative of the full set in terms of immu-conditions, we should expect to see the BORR for this subset to be somewhat close to that for the full set, given your theory is correct. This 33%<50% is a little bit weird.

Of course, the fact that 33%<50% may be just due to statistical errors and could be better purged in PISCES with larger cohorts to recover the true treatment effect of IL-12 on actual checkpoint progressors.

The true treatment effect on actual checkpoint progressors, in my viewpoint, is the ultimate variable of interest, for determining the value of the combination therapy, which would constitute a major share of Oncs total value based on current information.

Meanwhile, we will get a better sense of the value of the multigene platform during the SITC meeting.

[staccani]

hsclausch, do you realize that ONCS trial enrolled patients having mostly stage 3b and 3c disease (locally advanced / intransit disease) for which electroporation method of delivery is more indicated?
This is very different from stage IV patients (metastatic disease) of DVAX and IDRA trials. Moreover ONCS enrolled patients 'likely' refractory to anti pd1. This is very different from patients ACTUALLY progressing on anti pd1 as in IDRA trial and as in the subset of DVAX trial.
Finally you mention that IDRA responders will eventually progress due to progressive upregulation of pdl1. Whilst this may or may not happen (the fact that they were anti pd1 refractory leads me to believe that they were not positive to pdl1 in the first place), should it happen that they become progressively pdl1 positive, then an anti pd1 could be used either alone or in combination with their TLR9 agonist

Also for your reference have a look at the small DVAX subset of anti pd1 naive metastatic melanoma patients dosed with their TLR9 agonist in combination with an anti pd1 ... 7 out of 7 (100%) responders (!)http://files.shareholder.com/downloads/DVAX/5538749572x0x945135/FC57C254-FEF8-4D64-BBB4-E11B1E8F19DF/17-1361_ASCO_MEL-01_Final.pdf

It appears to me ONCS is fooling retail investors or anyway investors not expert of melanoma and cancer in general, whilst TLR9 agonists (of which DVAX has also a convenient aereosol delivery system for lung cancers) are the real promising ones in combo with CPI's for metastatic cancers.

[jondoeuk]

One patient had a CR (ongoing). He was 68 with mets to one lung (bulky), LN and soft tissue. Prior therapy with 4 doses of Nivo + Urelumab (anti-4-1BB) which failed http://www.iderapharma.com/wp-content/uploads/2017/09/A-Phase-1-2-Trial-of-Intratumoral-IMO-2125-IMO-in-Combination-with-Checkpoint-Inhibitors-CPI-in-PD-L1-refractory-Melanoma.pdf