RE:One horrible way Looks like a "just in case study" for a targeted therapy that was mainly directed at Ovarian Cancer though. Literature was "reporting" overexpression in TNBC so they went ahead on just that, and then stopped early. Kinda sloppy.
In contrast, TNBC will be the primary target of TH1902, and the groundwork on sortilin overexpression is solid. See AACR2 poster #4472:
B. TNBC patient survival (high vs. low sortilin expression)
Kaplan-Meier curves show that high sortilin gene expression is
associated with a poor prognosis for TNBC patients with
advanced disease (stage 3 or 4) (n=161)
Kaplan-Meier analysis of TNBC patients with lymph node
metastases (n=72) shows a drastic effect of high sortilin gene
expression on patient survival
The same poster also shows overexpression in 6 different TNBC cell lines.
It's also worth remembering that the preclinical mouse models demonstrated efficacy in two different TNBC cell lines (MDA-MB-231 cells and HCC-70)
Based on that, I wouldn't be too worried on the reality of SORT1 overexpression in TNBC.
Phase 1 success rate is 62.8% in Oncology, and I believe the probability is much higher here due to the usage of a well known taxane and solid preclinical work. Phase 1 is mainly about characterizing safety and PK/PD in humans after all..