ORIC Pharmaceuticals Presents Preclinical Data on Glucocorticoid Receptor Antagonist and CD73 Inhibitor Programs at AACR-NCI-EORTC Annual Conference
Evidence from the lead program showed that glucocorticoids promote the growth of prostate tumor cells, stimulate androgen-regulated gene expression and stimulate enzalutamide resistance, which ORIC-101 has completely reversed.
Second program data showed that small molecule inhibition of CD73 fully restored proliferation and cytokine production of T cells with AMP/adenosine suppression.
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 in Phase 1b – and its CD73 inhibitor program – an orally bioavailable small molecule inhibitor of a key node in the adenosine pathway – at the AACR-NCI-EORTC International Conference on Molecular Targets & Cancer Therapeutics in Boston, Massachusetts.
Glucocorticoid Receptor Antagonist Program
The ORIC-101 preclinical data were presented in abstract LB-A10, "ORIC-101 Overcomes Glucocorticoid-Driven Resistance to Enzalutamide in Castration-Resistant Prostate Cancer."
The glucocorticoid receptor has been identified as a potential antiandrogen bypass mechanism in patients with castration-resistant prostate cancer; thus GR-targeted therapies may overcome this therapeutic resistance to restore or prolong antiandrogen sensitivity. The poster presentation showed that GR is widely expressed in prostate cancer cell lines, organoids, and tumor tissue, and that GR levels are upregulated upon enzalutamide treatment. The data demonstrated that glucocorticoids promote tumor cell growth, stimulate expression of androgen regulated genes, and drive resistance to enzalutamide. Importantly, these effects were completely reversed by ORIC-101, suggesting ORIC-101 overcomes GR-driven resistance to enzalutamide.
ORIC-101 is currently in a Phase 1b study in combination with nab-paclitaxel in patients with advanced solid tumors. ORIC also plans to initiate a second Phase 1b study of ORIC-101 in combination with enzalutamide in patients with metastatic prostate cancer in the fourth quarter of 2019.
CD73 Inhibitor Program
Preclinical data from ORIC's second program were presented in abstract LB-A19, "Intratumoral Immunosuppression is Reversed by Blocking Adenosine Production with an Oral Inhibitor of CD73."
The poster presentation showed that CD73 can drive adenosine generation from adenosine monophosphate (AMP) in vitro, resulting in suppression of anti-CD3/CD28-induced T cell activation and proliferation. The findings indicated that a novel, orally bioavailable CD73 inhibitor was able to effectively inhibit AMP to adenosine conversion both in vitro and in vivo, while an anti-CD73 antibody had incomplete effects. Small molecule-based inhibition of CD73 also fully restored proliferation and cytokine production of AMP/adenosine-suppressed T cells. Based on these results, an orally bioavailable small molecule inhibitor of CD73 represents a potential therapeutic approach to reverse immunosuppression within the tumor microenvironment.
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/.
Dominic Piscitelli, Chief Financial Officer
SOURCE ORIC Pharmaceuticals