ORIC-533

P1, N=56, Active, not recruiting, ORIC Pharmaceuticals | Recruiting --> Active, not recruiting | Phase classification: P1b --> P1 | Trial completion date: Jun 2024 --> Sep 2024 | Trial primary completion date: Jun 2024 --> Sep 2024

No abstract available

This study, together with our previous reports, confirms that CD73 inhibition can reduce adenosine generation, overcome immune suppression, and restore lysis of MM cells. Based on these results, ORIC-533 is being studied as a single agent in a Phase 1 clinical trial in patients with relapsed or refractory multiple myeloma.

Recent clinical proof of concept data demonstrated a significant improvement in progression free survival for non-small cell lung cancer patients upon targeting CD73 with the oleclumab anti-CD73 antibody in combination with anti-PDL1, relative to anti-PDL1 checkpoint inhibitor treatment alone.We developed ORIC-533, a potent, orally bioavailable, AMP-competitive, small molecule inhibitor of CD73, that is highly selective for CD73 and exhibits picomolar potency in biochemical assays, completely blocking adenosine production from AMP. Taken together, these results demonstrate that the ORIC CD73 inhibitor potently inhibits the adenosine pathway, which restores anti-tumor immunity and therefore holds potential for patients with MM. Based upon these data, ORIC-533 is being studied as a single agent in a Phase 1 clinical trial in patients with relapsed or refractory multiple myeloma.

This study therefore demonstrates that: 1. CD73-mediated adenosine activity suppresses the cytolytic activity of T-cells against tumor cells in the MM BM milieu; and 2. CD73 inhibition can overcome immune suppression and restore lysis of MM cells by autologous T-cells.

Taken together, these preclinical results indicate the CD73 inhibitor ORIC-533 has best-in-class properties in reversing immunosuppression in tumors. ORIC-533 is currently undergoing GLP studies to support an IND filing in the first half of 2021.