ORIC Pharmaceuticals Presents Preclinical Data on Glucocorticoid Receptor Antagonist and CD73 Inhibitor Programs at the 2020 American Association for Cancer Research Virtual Annual Meeting II
ORIC Pharmaceuticals presented encouraging preclinical data for its ORIC-101 glucocorticoid receptor antagonist and ORIC-533 CD73 inhibitor at the AACR Virtual Annual Meeting II. ORIC-101 showed the ability to reverse GR-mediated resistance across various tumor models, which is critical in cancer treatment. The ongoing Phase 1b trials with enzalutamide and nab-paclitaxel aim to further assess its effectiveness. Meanwhile, ORIC-533 has demonstrated notable potency in inhibiting adenosine production, with potential benefits for immunotherapy and anti-tumor responses.
- ORIC-101 reversed GR-mediated resistance in multiple tumor models.
- Ongoing Phase 1b trials for ORIC-101 with enzalutamide and nab-paclitaxel.
- ORIC-533 showed sustained inhibition of adenosine production post-drug washout.
- ORIC-533 effectively inhibited tumor growth and reduced immunosuppression.
- None.
SOUTH SAN FRANCISCO, Calif., June 22, 2020 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today presented preclinical data from the company’s glucocorticoid receptor (GR) antagonist and CD73 inhibitor programs in five poster presentations during the ongoing American Association for Cancer Research (AACR) Virtual Annual Meeting II.
“We are pleased to be able to present these compelling preclinical data from our ORIC-101 and CD73 programs, which continue to validate our scientific platform focused on overcoming therapeutic resistance in cancer,” said Lori Friedman, chief scientific officer. “In particular, we are encouraged to see ORIC-101 reversing GR-mediated resistance in a variety of tumor models, and preliminary evidence of differentiation of ORIC-533 versus competitor compounds in preclinical studies. We look forward to the continued advancements of these programs and our discovery research pipeline as we work to improve patients’ lives.”
ORIC-101 (GR Antagonist):
ORIC-101 is a potent and selective small molecule antagonist of GR, which has been linked with resistance to multiple classes of cancer therapeutics across a variety of solid tumors. ORIC-101 is currently being investigated in two separate Phase 1b combination trials, with enzalutamide in prostate cancer and with nab-paclitaxel in solid tumors.
Key findings of the presentations:
- A transcriptional signature of GR activity was identified in a panel of 32 cell lines across triple negative breast cancer, non-small cell lung cancer and pancreatic ductal adenocarcinoma, which translated from preclinical models to human tumors
- ORIC-101 overcame GR-mediated resistance to chemotherapeutic agents including taxanes, antimetabolites and platinums, in both in vitro and in vivo efficacy studies spanning a variety of solid tumor types
- Transcriptional and histological profiling showed that ORIC-101 reversed GR-activated pathways involved in drug resistance, and reversed in vivo markers of epithelial-to-mesenchymal transition, antiapoptosis, and hypoxia
- The company is further assessing the GR activation signature and mechanistic findings in an ongoing Phase 1b trial of ORIC-101 in combination with nab-paclitaxel in adults with advanced or metastatic solid tumors
Poster Presentations:
- ORIC-101 comprehensively inhibits glucocorticoid pathways to overcome therapeutic resistance in pan-cancer models (Poster #4120)
- ORIC-101 overcomes resistance to diverse chemotherapeutics across cancer types (Poster #4121)
- ORIC-101 overcomes glucocorticoid receptor-mediated chemoresistance in pancreatic cancer models (Poster #4123)
ORIC-533 (CD73 Inhibitor):
CD73 is a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy and immunotherapy. ORIC discovered and characterized differentiated orally bioavailable small molecule inhibitors of CD73, including clinical candidate ORIC-533, that revert immunosuppression and promote anti-tumor responses in vivo.
Key findings of the presentations:
- ORIC’s CD73 inhibitors demonstrated suppression of adenosine production in vitro across multiple cell types and rescued activation of CD8+ T cells exposed to AMP with greater potency than competitor compounds
- ORIC-533 was shown to result in sustained inhibition of adenosine production after drug washout, consistent with its slow off-rate, and differentiating from other CD73 inhibitors
- ORIC-533 potency in high AMP environments distinguishes it from other compounds, with activity in AMP concentrations as high as 1 millimolar, which may better reflect certain tumor microenvironments
- Daily oral delivery of ORIC’s CD73 inhibitors significantly inhibited tumor growth, with corresponding in vivo reduction of adenosine levels in tumors, and immune modulation consistent with decreased immunosuppression
Poster Presentations:
- CD73 inhibition with a novel orally bioavailable small molecule blocks adenosine production and rescues T-cell activation (Poster #1023)
- An orally bioavailable inhibitor of CD73 reverts intratumoral immunosuppression and promotes anti-tumor response (Poster #LB-115)
About ORIC Pharmaceuticals, Inc.
ORIC Pharmaceuticals is a clinical stage biopharmaceutical company dedicated to improving patients’ lives by Overcoming Resistance In Cancer. ORIC’s lead product candidate, ORIC-101, is a potent and selective small molecule antagonist of the glucocorticoid receptor, which 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 (1) Xtandi (enzalutamide) in metastatic prostate cancer and (2) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors. ORIC’s second product candidate, ORIC-533, is an orally bioavailable small molecule inhibitor of CD73, a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy- and immunotherapy-based treatment regimens. Beyond these two product candidates, ORIC is also developing multiple precision medicines targeting other hallmark cancer resistance mechanisms. ORIC has offices in South San Francisco and San Diego, California. For more information, please go to http://oricpharma.com/.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements about ORIC as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, statements regarding ORIC’s development plans; the ability of ORIC-101 and ORIC’s CD73 inhibitors to overcome resistance in cancer models; plans underlying ORIC-101 clinical trials and development; preclinical data and plans underlying ORIC-533; and the potential advantages of ORIC’s product candidates. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained herein are based upon ORIC’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early clinical stage company; ORIC’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; changes in ORIC’s plans to develop and commercialize its product candidates; the potential for clinical trials of ORIC-101 or any future clinical trials of other product candidates to differ from preclinical, preliminary or expected results; negative impacts of the COVID-19 pandemic on ORIC’s operations, including clinical trials; ORIC’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; ORIC’s reliance on third parties, including contract manufacturers and contract research organizations; ORIC’s ability to obtain and maintain intellectual property protection for its product candidates; the loss of key scientific or management personnel; competition in the industry in which ORIC operates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in ORIC’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on May 20, 2020, and ORIC’s future reports to be filed with the SEC. These forward-looking statements are made as of the date of this press release, and ORIC assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.
Contact:
Dominic Piscitelli, Chief Financial Officer
dominic.piscitelli@oricpharma.com
info@oricpharma.com
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