Another Target Expression Comparison: Trop-2So we learned from THTX that sortilin overexpression is 3x that of PD-1 (Keytruda's target) in tumors. I found some data on Trop-2 (Trodelvy's target), but I wouldn't know how to compare that to sortilin like THTX did in their paper. But there's a few clues.
One thing I noticed about TROP-2 is that it appears to be located in a lot of other spots around the body and has a decent amount of expression in normal human tissue in various organs. This is likely why IMMU ran in to a lot of safety issues early on. It still has a fairly high safety signal issue and is not SAE free.
The other thing I noticed from one of the papers is that while TROP-2 is a target in lots of cancer types (just like SORT1) and Gilead is now doing all those trials, for TNBC TROP-2 is not overexpressed in 3 of the breast cancer tumor lines. I think there's something like 6 or so typical lines but I could be wrong. It seems to be fairly typical that the overexpression of a target doesn't always appear in all tumor line types across all the different tumors. So we ought to expect they learn which lines it works best on and which it doesn't for TH1902. We shouldn't expect it works on all the various tumor lines as effectively, but I could be wrong. I'd rather go in to the trial with that understanding and be positively surprised. That's a big part of the response rate I would presume, where Trodelvy is only in the 30%ish response level. We can hope TH1902 improves on this by a lot, and that would be meaningful in the hospital.
So from two different studies, TROP-2 was overexpressed in roughly 37% of TNBC patients. It had moderate expression in 23% and little to none in 40%. If I look down the list of all the various cancers, the percent of patients with TROP-2 high overexpression is in the 15-40% range and moderate is in the 20-30% range. This includes pancrease, stomach, ovarian, prostate, colon, lung, etc...
By way of comparison, we've heard THTX state that SORT1 is overexpressed in 40-90% of the patients in the 4 cancers in the upcoming basket trial. I believe TNBC is 60% (80% for invasive ductal BC), ovarian is 90-100%, endometrial is 90%, urothelial is 70%, melanoma 90% and colorectal and pancreatic are 30%. Just looking at that, there is at least a possibility to see a much higher response rate targeting SORT1 versus TROP-2 in TNBC and certainly in some of the others like ovarian and endometrial. But as to the actual amounts of TROP-2 seen in these tumors versus SORT1 seen on them, I don't know how to find that calculation. Maybe THTX can add that in to their next presentation along with the PD-1 comparison that they've already published.
Nonetheless, there's two things going for SORT1 versus TROP-2 -- the fact TROP-2 is prevalent all over the body and in some meaningful numbers, thus causing safety issues, and at least in TNBC, ovarian and endometrial, more tumors seem to overexpress SORT1 versus TROP-2. Those are the cancers they're targeting in 1b onward.