CD73 inhibition overcomes immunosuppression and demonstrates activity in assays derived from relapsed or refractory multiple myeloma patients, offering the potential for single agent activity in the clinic
Phase 1 trial
CD73 inhibition overcomes immunosuppression and demonstrates activity in assays derived from relapsed or refractory multiple myeloma patients, offering the potential for single agent activity in the clinic
Phase 1 trial of single agent ORIC-533, a highly potent, orally bioavailable small molecule inhibitor of CD73, expected to initiate in 4Q 2021 in patients with multiple myeloma
Conference call and webcast today at 5:30 p.m. ET
SOUTH SAN FRANCISCO and SAN DIEGO, Calif., Dec. 13, 2021 (GLOBE NEWSWIRE) — ORIC Pharmaceuticals, Inc. (NASDAQ:ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance presented preclinical data with ORIC’s small molecule inhibitor of CD73 in multiple myeloma at the American Society of Hematology (ASH), in collaboration with Dr. Kenneth Anderson’s research laboratory at Dana-Farber Cancer Institute. The abstract and presentation are available for online viewing via the ASH Annual Meeting website.
“ORIC-533 has a differentiated profile, demonstrating stronger potency in a high AMP environment compared to benchmark CD73 inhibitors and adenosine receptor antagonists in preclinical studies,” said Lori Friedman, chief scientific officer. “Based on a strong mechanistic rationale and compelling single agent activity in patient-derived autologous ex vivo assays, we are excited to pursue clinical development in multiple myeloma.”
Multiple myeloma patient samples have demonstrated that the tumor environment is adenosine rich, and studies have shown that high CD73 and adenosine levels are associated with poor prognosis and therapeutic resistance.
The ASH presentation focused on the role of adenosine signaling in immunosuppression in patients with relapsed or refractory multiple myeloma and the ability of ORIC’s small molecule inhibitor of CD73 to restore antitumor immune activity.
Key highlights from a series of experiments utilizing bone marrow aspirates from patients with multiple myeloma include:
- CD73 inhibition addressed adenosine mediated immunosuppression, which stimulated T-cell proliferation, T-cell activation, and activation of plasmacytoid dendritic cells in ex vivo assays derived from patients with multiple myeloma.
- ORIC’s small molecule inhibitor of CD73 overcame immunosuppression and triggered significant lysis and cell death of multiple myeloma cells by autologous T-cells from the bone marrow microenvironment.
- ORIC’s CD73 inhibitor demonstrated single agent activity, comparing favorably to standard of care therapies, in bone marrow-derived mononuclear cell assays from relapsed or refractory myeloma patients.
The company plans to pursue a single agent clinical development plan for ORIC-533 in multiple myeloma and initiate a Phase 1 trial in the fourth quarter of 2021.
Additional Pipeline Updates:
ORIC-114 EGFR/HER2 Inhibitor
ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations. The company recently disclosed that ORIC-114 induced tumor regressions in a subcutaneous HER2 positive breast cancer xenograft model. In a new study, ORIC-114 demonstrated significant tumor growth inhibition in an intracranial HER2 positive breast cancer model, with superior antitumor activity versus tucatinib. The CTA has been filed in South Korea, and initiation of a Phase 1 trial is expected in early 2022.
ORIC-944 PRC2 Inhibitor
ORIC-944 is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2) that targets its regulatory embryonic ectoderm development (EED) subunit and has demonstrated single agent efficacy in multiple enzalutamide-resistant prostate cancer models in preclinical studies. The IND was cleared by the FDA in December, and initiation of a Phase 1 trial is expected in early 2022.
Webcast and Conference Call Details
ORIC will host a conference call and webcast, today at 5:30 p.m. ET. To participate in the conference call, please dial (833) 651-0991 (domestic) or (918) 922-6080 (international) and refer to conference ID 7989199. A live webcast and audio archive of the conference call will be available through the investor section of the company’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.
Recent Comments