ORIC Pharmaceuticals, Inc. (NASDAQ:ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today announced a poster presentation and oral discussion at the upcoming 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics being held virtually October 24 - 25, 2020. The presentation will highlight preclinical data in prostate cancer cell lines that demonstrate the company’s glucocorticoid receptor (GR) antagonist, ORIC-101, reversing GR-mediated resistance to an androgen receptor (AR) degrader.
In the study, it was observed that upon treatment of prostate cancer cell lines with an AR degrader, GR mRNA and protein levels were significantly upregulated, similar to the GR upregulation seen after dosing with enzalutamide. This GR upregulation translated into GR activation that conferred resistance to the AR degrader, permitting prostate cancer cells to continue to grow. ORIC-101 was shown to completely reverse these effects and block tumor cell growth and androgen-regulated gene expression. These data demonstrate that GR may be a mechanism of resistance to AR degraders and that in vitro, ORIC-101 overcomes GR-driven resistance to AR degradation.
GR has been linked to resistance to multiple classes of cancer therapeutics across a variety of solid tumors. ORIC-101 is currently in two separate Phase 1b trials of ORIC-101 in combination with Xtandi (enzalutamide) in metastatic prostate cancer and Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors. ORIC expects to report interim data from one of the trials in the first half of 2021 and from the other trial in the second half of 2021.
Details of the poster presentation are as follows:
Title: ORIC-101 Overcomes GR-driven Resistance to AR Degradation in Castration-Resistant Prostate Cancer Models
Date: October 25, 2020; 2:30 p.m. CEST
Session: Poster Discussion Session
Topic: Approaches to Overcoming Therapeutic Resistance