OncoSec Medical Inc (ONCSQ)

[hschlauch]

Idera has developed an intratumorally-delivered TLR9 agonist that they are currently testing in a clinical trial. They are enrolling anti-PD-1 refractory metastatic melanoma patients into two arms in a phase 1/2 trial - one is an Ipi/IMO-2125 combo and the other is a Nivo/IMO-2125 combo. No results have been posted yet for the Nivo/IMO-2125 arm.

Updated results for the Ipi/IMO-2125 arm show 50% overall response rate and 0% complete responses. No data have been posted yet for duration of responses.

I think the Ipi/IMO-2125 arm will end up with responders mostly progressing due to the PD-1 upregulation over time. The Ipi/IMO-2125 arm will be a dead end in my opinion. And systemic anti-CTLA-4 leads to many SAEs. Yet, Baker Bros own over 10 million shares of Idera.

Even though there are no data yet on the Nivo/IMO-2125 trial arm, I think we can predict how well it will do by looking at Dynavax's KEYNOTE-184 trial. There was a 12-patient subset with metastatic melanoma that failed anti-PD-1 therapy and were subsequently treated with SD-101 (intratumoral TLR9) and Keytruda. Tumors shrunk in 42% of patients, but only 17% actually had a partial response. There were no complete responders among these patients either.

Also, don't forget, UCSF/Oncosec had intentionally selected patients who were the worst of the worst immunologically for the Immunopulse IL-12 with pembro predicted nonresponder trial. Many of these patients had no detectable exhausted T cells present at baseline. Again, this is the reason I think the PISCES trial will do so well - they won't be so restrictive with their enrollment criteria.

Also, just a side note... intratumoral expression of an anti-CTLA-4 checkpoint inhibitor encoded on a polycistronic plasmid vector will be much more effective and safer than the systemic route. If Oncosec includes this in any of their new PIIM constructs, we will likely see most if not all patients becoming complete responders in my opinion. This would easily drive the company's valuation well into the tens of billions of dollars, because the platform could be applied to any solid tumor type. I've said this before and I will say it again, these PIIM constructs are going to be completely disruptive.