Orally bioavailable small molecule CD73 inhibitors reverse immunosuppression by blocking adenosine production
Internal research program led to discovery of clinical candidate ORIC-533, which in preclinical studies demonstrated significant anti-tumor single agent efficacy
SOUTH SAN FRANCISCO, CA, USA I April 27, 2020 I ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today presented 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) Virtual Annual Meeting I.
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.
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’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’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. ORIC has offices in South San Francisco and San Diego, California. For more information, please go to http://oricpharma.com/.
SOURCE: ORIC Pharmaceuticals
Post Views: 29
Orally bioavailable small molecule CD73 inhibitors reverse immunosuppression by blocking adenosine production
Internal research program led to discovery of clinical candidate ORIC-533, which in preclinical studies demonstrated significant anti-tumor single agent efficacy
SOUTH SAN FRANCISCO, CA, USA I April 27, 2020 I ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today presented 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) Virtual Annual Meeting I.
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.
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’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’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. ORIC has offices in South San Francisco and San Diego, California. For more information, please go to http://oricpharma.com/.
SOURCE: ORIC Pharmaceuticals
Post Views: 29
