ORIC-101 robustly inhibits the glucocorticoid pathway and overcomes chemoresistance in triple-negative breast cancer
SOUTH SAN FRANCISCO, CA, USA I December 16, 2019 I ORIC Pharmaceuticals, a privately held, clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, presented new preclinical data on its lead program, ORIC-101, a selective and potent glucocorticoid receptor (GR) antagonist currently being investigated in a Phase 1b clinical trial in combination with nab-paclitaxel in patients with advanced solid tumors, at the 2019 San Antonio Breast Cancer Symposium.
The ORIC-101 preclinical data were presented in a poster titled, “ORIC-101 Robustly Inhibits the Glucocorticoid Pathway and Overcomes Chemoresistance in TNBC” (Program Number: P6-03-24, Abstract #2507).
GR is highly expressed in a variety of cancers including prostate, pancreatic, ovarian, triple-negative breast cancer (TNBC) and endometrial cancers. Preclinical studies have indicated that activation of GR reduces the efficacy of chemotherapy, while inhibition of GR with the antagonist ORIC-101 enhances the efficacy of chemotherapy in multiple solid tumor models.
ORIC-101 potently sensitizes TNBC cells to chemotherapy by reversing GR-mediated resistance through the epithelial-to-mesenchymal transition and anti-apoptosis pathways, in both in vitro and in vivo preclinical models. The poster presented a GR activation signature developed at ORIC that includes the direct GR transcriptional targets FKBP5 and GILZ and subsequently validated both genes as ORIC-101 pharmacodynamic (PD) biomarkers. The relationship between PD biomarkers, pharmacokinetics and efficacy in preclinical models was also assessed. The data demonstrated that ORIC-101 robustly inhibits the transcriptional induction of PD biomarkers and fully reverses GR-mediated chemoresistance in vitro and in vivo.
In addition to its ongoing Phase 1b clinical trial of ORIC-101 in combination with nab-paclitaxel, ORIC is also conducting a second Phase 1b clinical trial of ORIC-101 in combination with enzalutamide in patients with metastatic prostate cancer.
About ORIC Pharmaceuticals
ORIC Pharmaceuticals is a privately held, clinical-stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance. ORIC’s lead program, ORIC-101, is a potent and selective small molecule antagonist of the glucocorticoid receptor, which has been linked to treatment resistance to multiple classes of anti-cancer therapeutics across a variety of solid tumors. ORIC’s pipeline also includes an orally bioavailable small molecule inhibitor of CD73, as well as other undisclosed programs targeting mechanisms of oncology therapeutic resistance. ORIC’s scientific founders, Charles Sawyers, MD, and Scott Lowe, PhD, have long records of discovering novel targets in cancer that have led to innovative treatments. The company has assembled strong leadership and scientific teams, and a board with extensive experience in drug development and financing. ORIC is funded by leading biotechnology investors and is headquartered in South San Francisco, California. For more information, please go to http://oricpharma.com/.
SOURCE: ORIC Pharmaceuticals
Post Views: 37
ORIC-101 robustly inhibits the glucocorticoid pathway and overcomes chemoresistance in triple-negative breast cancer
SOUTH SAN FRANCISCO, CA, USA I December 16, 2019 I ORIC Pharmaceuticals, a privately held, clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, presented new preclinical data on its lead program, ORIC-101, a selective and potent glucocorticoid receptor (GR) antagonist currently being investigated in a Phase 1b clinical trial in combination with nab-paclitaxel in patients with advanced solid tumors, at the 2019 San Antonio Breast Cancer Symposium.
The ORIC-101 preclinical data were presented in a poster titled, “ORIC-101 Robustly Inhibits the Glucocorticoid Pathway and Overcomes Chemoresistance in TNBC” (Program Number: P6-03-24, Abstract #2507).
GR is highly expressed in a variety of cancers including prostate, pancreatic, ovarian, triple-negative breast cancer (TNBC) and endometrial cancers. Preclinical studies have indicated that activation of GR reduces the efficacy of chemotherapy, while inhibition of GR with the antagonist ORIC-101 enhances the efficacy of chemotherapy in multiple solid tumor models.
ORIC-101 potently sensitizes TNBC cells to chemotherapy by reversing GR-mediated resistance through the epithelial-to-mesenchymal transition and anti-apoptosis pathways, in both in vitro and in vivo preclinical models. The poster presented a GR activation signature developed at ORIC that includes the direct GR transcriptional targets FKBP5 and GILZ and subsequently validated both genes as ORIC-101 pharmacodynamic (PD) biomarkers. The relationship between PD biomarkers, pharmacokinetics and efficacy in preclinical models was also assessed. The data demonstrated that ORIC-101 robustly inhibits the transcriptional induction of PD biomarkers and fully reverses GR-mediated chemoresistance in vitro and in vivo.
In addition to its ongoing Phase 1b clinical trial of ORIC-101 in combination with nab-paclitaxel, ORIC is also conducting a second Phase 1b clinical trial of ORIC-101 in combination with enzalutamide in patients with metastatic prostate cancer.
About ORIC Pharmaceuticals
ORIC Pharmaceuticals is a privately held, clinical-stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance. ORIC’s lead program, ORIC-101, is a potent and selective small molecule antagonist of the glucocorticoid receptor, which has been linked to treatment resistance to multiple classes of anti-cancer therapeutics across a variety of solid tumors. ORIC’s pipeline also includes an orally bioavailable small molecule inhibitor of CD73, as well as other undisclosed programs targeting mechanisms of oncology therapeutic resistance. ORIC’s scientific founders, Charles Sawyers, MD, and Scott Lowe, PhD, have long records of discovering novel targets in cancer that have led to innovative treatments. The company has assembled strong leadership and scientific teams, and a board with extensive experience in drug development and financing. ORIC is funded by leading biotechnology investors and is headquartered in South San Francisco, California. For more information, please go to http://oricpharma.com/.
SOURCE: ORIC Pharmaceuticals
Post Views: 37
