On September 21, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported an update on its CD73 inhibitor program (Press release, ORIC Pharmaceuticals, SEP 21, 2021, View Source [SID1234590063]). ORIC recently announced the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug Application (IND) for ORIC-533 to proceed into a first-in-human clinical trial in which ORIC-533 will be tested as a single agent in an undisclosed tumor type not currently known to be under clinical evaluation with any other CD73 inhibitor. ORIC-533 was discovered internally at ORIC, is wholly owned, and 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.
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In preclinical studies, ORIC-533 has demonstrated higher potency in a high AMP environment compared to all CD73 and adenosine receptor inhibitors against which it was compared, including both small molecules and antibodies, such as oleclumab. Preclinical data suggest ORIC-533 binds CD73 with high affinity and effectively blocks adenosine-driven immunosuppression. In preclinical studies, nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, reflective of AMP levels observed in tumors.
Based on a preclinical collaboration with an academic key opinion leader that generated compelling single agent activity in patient derived model systems in an undisclosed tumor type, the company plans to pursue a single agent clinical development plan in this indication. ORIC expects to enroll its first patient in this trial during the fourth quarter of 2021. Also during the fourth quarter of 2021, ORIC plans to host an R&D event during which it will disclose the tumor indication along with the supporting preclinical rationale and data.
The second quarter ORIC-533 IND filing was the first of three planned IND/CTA filings by ORIC in 2021, with the IND filing for ORIC-944 (allosteric inhibitor of PRC2) and CTA filing for ORIC-114 (brain penetrant inhibitor of EGFR and HER2, including exon 20 insertion mutations) expected in the fourth quarter of 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, other small molecule CD73 inhibitors and inhibitors of adenosine receptors. Preclinical data suggest ORIC-533 binds CD73 with high affinity and effectively blocks adenosine-driven immunosuppression in a high AMP environment. In preclinical studies, nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, reflective of AMP levels observed in tumors.