On November 3, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported a preclinical poster presentation on ORIC-533 at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held December 10-13, 2022, in New Orleans, LA (Press release, ORIC Pharmaceuticals, NOV 3, 2022, View Source [SID1234622913]).
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ORIC-533 continues to demonstrate a best-in-class CD73 inhibitor profile in preclinical analyses.
In autologous ex vivo assays using bone marrow aspirates from patients with relapsed refractory multiple myeloma, ORIC-533 overcame immune suppression and triggered significant lysis of multiple myeloma cells across all dose levels tested and in a dose-responsive manner.
Lysis of multiple myeloma cells in autologous relapsed refractory multiple myeloma assays correlated with significantly reduced CD73 activity, providing the mechanistic link between ORIC-533 and reduced adenosine production.
Together these data confirm that CD73 inhibition with ORIC-533 can potently reduce adenosine generation, overcome immune suppression and restore lysis of multiple myeloma cells as a single agent and therefore holds potential as a treatment for patients with multiple myeloma.
Full abstracts are available for online viewing via the ASH (Free ASH Whitepaper) Annual Meeting website at www.hematology.org/meetings/annual-meeting.
About ORIC-533
ORIC-533 is a highly potent, 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. ORIC-533 has demonstrated greater potency in preclinical studies compared to an antibody approach, as well as other small molecule inhibitors of CD73 and adenosine receptor antagonists. Preclinical data demonstrated that ORIC-533 binds CD73 with high affinity and effectively blocks adenosine-driven immunosuppression in a high AMP environment, reflective of AMP levels observed in tumors. In preclinical studies, nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, as well as in ex vivo bone marrow aspirates from relapsed or refractory multiple myeloma patients. A Phase 1b trial with ORIC-533 as a single agent in multiple myeloma is enrolling patients, and the company expects to report initial Phase 1b data from this trial in the first half of 2023.