Theratechnologies Inc T.TH

Another Target Expression Comparison: Trop-2

[Wino115]

So 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.

[Wino115]

[Wino115]

I really think THTX would benefit it's shareholders by trying to put Sort1 as a target in context with the two successful solid tumor drugs out there, Keytruda (PD-1) and Trodelvy (TROP-2).  It's similar to what we kept mentioning with NASH, if you can put some of your data up versus the well known and successful competitors it provides a ready-made investment thesis. You'd be

[qwerty22]

I totally agree. A head-to-head against Trop2/Trodelvy would be great. All you have to do is label it a drug with a $21billion price tag and it's pretty much validated for investors. As you show SORT1 appears to at least match Trop2 if not betters. As ever the real validation comes with their drug showing efficacy but there are obvious questions raised by this technology and I don't

[Wino115]

Let's hope Dubuc or PL/Marsolais read this! I do think this would be the most powerful to show it after any POC or efficacy data.  So they have time to put this through.  I suppose you could do a slide now that just puts context around the "not marginal" pitch they make -- show that first and use those comps.  Once you get efficacy, show those actual drugs, the lines

[jfm1330]

Where did Thera release that info?

[Wino115]

It is in the fourth section (Discussion) in their paper published in Cancer Science May 2021.  It's the second to last paragraph in the whole paper.  They mention that Sort1 was "upregulated" in around 60% of TNBC subtypes while PD-1 was upregulated in only 19% of TNBC.  THTX's 60% in TNBC is from the paper by Roselli & Pundavela (Oncotarget 2015, Sortilin is

[jfm1330]

I see. It is important to specify here that they state that sortilin is expressed in 59% of all TNBC subtypes, compare to PD-1 expressed in 19% of cancer subtypes. So it is not an expression of the receptor itself that is three times higher in TNBC. In other words, it is not three times more sortilin receptors on membranes of TNBC cells in general. I just specify that because when I read you first