Thanks for sharing the updated corporate presentation. I have been "in the trenches" for a few days, so I haven't really had the chance to review the presented results until now.
The presented data, albeit preliminary and a small dataset, definitely appear to demonstrate efficacy improvements over what would be expected of monotherapy keytruda, or any monotherapy anti-pd1 treatment for that matter. Although it hasn't been discussed much, I think the individual duration of response data seem to be very intriguing for those patients who have been treated beyond 3-4 months; none of these patients are progressing once they respond. Long term follow up is obviously needed, but response durations thus far indicated are remarkable.
Also, like I said before, the complete responses really stand out for me, and they're occurring in patients with relatively low pd1/ctla4-hi positive TIL baselines.
In terms of the non-responders in this trial, most of whom were previously treated with anti-pd1 therapy, suggests to me that these patients are having a hard time getting their pd1/ctla4-hi positive TIL up in the right territory (>30%-positive TIL) and/or the TIL are landing in that 20%-29% zone where responses are less predictable.
I have also read published studies that describe how tumors can develop adaptive resistance to prolonged anti-pd1 therapies. For example in Koyama, S. et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat. Commun. 7:10501 doi: 10.1038/ncomms10501 (2016), data suggest that there is an upregulation of TIM-3 expression on T-cells following prolonged exposure to pd-1 immune checkpoint inhibitors, noted in lung cancer patients. If this is the case with the non-responders in ONCS's combination phase II metastatic melanoma trial, then it stands to reason that to turn these particular patients into responders ONCS might have to use a combination of checkpoint inhibitors to attack multiple pathways OR use EP IL-12 plasmid DNA plus pembrolizumab in a first line setting. While it is apparent that a certain percentage of these previously treated anti-pd-1 patients are responding, I think the combination therapy may work even better in a first line setting or in combination with additional checkpoint inhibitors in a second line setting. Again, this is just in my non-professional opinion.
