On April 27, 2020 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported research that led to the discovery of potent and orally bioavailable small molecule inhibitors of CD73 at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I (Press release, ORIC Pharmaceuticals, APR 27, 2020, View Source [SID1234561053]).
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The preclinical data on ORIC’s CD73 program were presented in the "Advances in Cancer Drug Design and Discovery" session in an oral presentation titled "Orally Available Small Molecule CD73 Inhibitor Reverses Immunosuppression Through Blocking of Adenosine Production" (Abstract #1242, presentation 1037).
Many cancers usurp the anti-inflammatory adenosine pathway to avoid detection by the immune system, thereby reducing the effectiveness of certain chemotherapy- and immunotherapy-based treatments. Accumulation of adenosine in the tumor microenvironment is implicated in local immune suppression that leads to tumor growth. CD73 is an enzyme that controls the rate at which extracellular adenosine is produced and its overexpression is associated with poor prognosis in several cancers, including triple negative breast cancer, non-small cell lung cancer, melanoma and prostate cancer, among others. Therefore, reducing the level of adenosine via inhibition of CD73 has become a potential strategy for cancer treatment.
ORIC’s small molecule inhibitor of CD73 demonstrated more potent adenosine inhibition compared to an antibody approach in preclinical studies. Further studies showed CD73 inhibition impacted T cell proliferation and cytokine production in the context of adenosine-mediated immunosuppression. ORIC’s research program led to the discovery of clinical candidate ORIC-533, an orally bioavailable small molecule inhibitor of CD73, which in preclinical studies demonstrated significant anti-tumor single agent efficacy when dosed once a day, with corresponding reduction of adenosine levels in the tumor microenvironment. ORIC expects to file an IND for ORIC-533 in the first half of 2021.