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ORIC Pharmaceuticals Presents Posters on Four Programs at the 2021 American Association for Cancer Research (AACR) Annual Meeting

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SOUTH SAN FRANCISCO and SAN DIEGO, April 12, 2021 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (NASDAQ:ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of resistance in cancer, presented four preclinical poster presentations at the 2021 American Association for Cancer Research (AACR) virtual annual meeting.

ORIC-101: Glucocorticoid Receptor (GR) Antagonist
ORIC-101 is a potent and selective GR antagonist, with two distinct mechanisms of action being evaluated in two Phase 1b trials in combination with: (1) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors and (2) Xtandi (enzalutamide) in metastatic prostate cancer.

Key findings of the presentation:

  • GR upregulation and activation, an established resistance mechanism for antiandrogens, may drive resistance when antiandrogens are combined with AKT inhibitors.
  • ORIC-101 was able to overcome this resistance and restore antitumor activity in preclinical prostate cancer cell lines.

Poster Presentation:

ORIC-533: CD73 Inhibitor
ORIC-533 is a highly potent, orally bioavailable CD73 inhibitor and has demonstrated greater potency in preclinical studies compared to an antibody approach and other small molecule CD73 inhibitors.

Key findings of the presentation:

  • Nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, reflective of levels observed in tumors.
  • Inhibitors of adenosine receptors A2A or A2A/B were only able to rescue CD8+ T-cell function in the context of low micromolar AMP, thus may be ineffective in tumors with moderate or high AMP and adenosine levels.
  • ORIC-533 has potential best-in-class properties in reversing immunosuppression in tumors.

Poster Presentation:

ORIC-944: PRC2 Inhibitor  
ORIC-944 is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2) and targets its regulatory embryonic ectoderm development (EED) subunit.

Key findings of the presentation:

  • ORIC-944 has potential best-in-class drug properties compared to first generation PRC2 inhibitors, including a clean CYP profile.
  • ORIC-944 demonstrated superior activity compared to an EZH2 inhibitor in an in vivo DLBCL model.
  • ORIC-944 demonstrated strong tumor growth inhibition as a single agent with once daily dosing in both enzalutamide-responsive and enzalutamide-resistant in vivo prostate cancer models.

Poster Presentation:

ORIC-114: EGFR/HER2 Inhibitor
ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations.

Key findings of the presentation:

  • ORIC-114 is highly selective for the EGFR family of receptors with superior kinome selectivity compared to other exon 20 inhibitors.
  • ORIC-114 demonstrated low nanomolar potency across exon 20 insertion variants in biochemical and cell-based assays.  
  • Significant tumor regression was observed in multiple EGFR exon 20 patient-derived xenograft models using once daily oral administration of ORIC-114.
  • ORIC-114 displayed superior brain exposure relative to other compounds targeting exon 20 insertion mutations, and greater activity compared to other EGFR inhibitors in an intracranial NSCLC EGFR mutant xenograft model.

Poster Presentation:

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 in combination with (1) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors and (2) Xtandi (enzalutamide) in metastatic prostate cancer. ORIC's other product candidates include (1) ORIC-533, 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, (2) ORIC-944, an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the EED subunit, being developed for prostate cancer, and (3) ORIC-114, a brain penetrant inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations, being developed across multiple genetically defined cancers. Beyond these four 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 www.oricpharma.com.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements 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 the potential advantages of ORIC's product candidates and programs, including potential best-in-class differentiation; and plans underlying ORIC-101, ORIC-533, ORIC-944, ORIC-114 or any other programs. 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 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; the risk of the occurrence of any event, change or other circumstance that could give rise to the termination of ORIC's license agreements; 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 Annual Report on Form 10-K filed with the Securities and Exchange Commission (the "SEC") on March 23, 2021, 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.

Investor Contact:
Dominic Piscitelli, Chief Financial Officer
dominic.piscitelli@oricpharma.com
info@oricpharma.com

 


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