On November 4, 2021 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 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held December 11-14, 2021, in Atlanta, GA (Press release, ORIC Pharmaceuticals, NOV 4, 2021, View Source [SID1234594368]).

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Details of the poster presentation are as follows:

Title: CD73 inhibition overcomes immunosuppression and triggers autologous T-cell mediated multiple myeloma cell lysis in the bone marrow milieu
Abstract #: 2675
Date & Time: Sunday, December 12, 2021, 6:00 – 8:00 pm ET
Session: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational:
Poster II in Hall B5, Georgia World Congress Center
The presentation, in collaboration with Dr. Kenneth Anderson’s research laboratory at Dana-Farber Cancer Institute, will focus on the role of adenosine signaling in immunosuppression in patients with multiple myeloma and the ability of single agent CD73 inhibition to restore antitumor immune activity.

Key points of the abstract include:

In bone marrow aspirates from patients with relapsed or refractory multiple myeloma, an autologous ex vivo assay system comprising the multiple myeloma bone marrow milieu demonstrated that CD73-mediated adenosine activity suppressed the cytolytic activity of T-cells against tumor cells.
CD73 inhibition triggered activation of plasmacytoid dendritic cells and stimulated T-cell activation in ex vivo assays of multiple myeloma bone marrow microenvironment.
ORIC’s small molecule inhibitor of CD73 overcame immune suppression and triggered significant lysis and cell death of multiple myeloma cells by autologous T-cells in the bone marrow microenvironment.
Full abstracts are available for online viewing via the ASH (Free ASH Whitepaper) Annual Meeting website at www.hematology.org/meetings/annual-meeting. The Phase 1 trial of single agent ORIC-533 in patients with multiple myeloma is expected to initiate in 4Q 2021.

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.