On December 13, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported preclinical ORIC-533 data demonstrating a potential best-in-class CD73 inhibitor profile for the treatment of multiple myeloma (Press release, ORIC Pharmaceuticals, DEC 13, 2022, View Source [SID1234625220]).

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"ORIC-533 continues to demonstrate strong potency in reducing adenosine generation and thereby overcoming immune suppression and restoring lysis of multiple myeloma cells as a single agent in ex vivo models," said Jacob M. Chacko, MD, chief executive officer. "We look forward to sharing initial clinical data from the ongoing Phase 1b study of ORIC-533 in patients with multiple myeloma in the first half of 2023."

The ASH (Free ASH Whitepaper) presentation focused on ex vivo proof-of-concept studies with CD73 inhibitors using autologous bone marrow samples derived from patients with multiple myeloma.

Key highlights from the presentation include:

Preclinical analyses continue to show ORIC-533 demonstrates a potential best-in-class CD73 inhibitor profile.
ORIC-533 overcame immune suppression and triggered significant lysis of multiple myeloma cells across all dose levels tested and in a dose-responsive manner, in an autologous ex vivo assay using samples derived from bone marrow aspirates from patients with relapsed refractory multiple myeloma.
Together these preclinical data confirm that single agent ORIC-533 inhibits CD73 to potently reduce adenosine generation, overcome immune suppression and restore lysis of multiple myeloma cells and therefore holds potential as a treatment for patients with multiple myeloma.
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.