A novel small molecule inhibitor of CD73 triggers immune-mediated multiple myeloma cell death

Blood Cancer J. 2024 Apr 9;14(1):58. doi: 10.1038/s41408-024-01019-5.

¹ The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. arghya_ray@dfci.harvard.edu.
² The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
³ ORIC Pharmaceuticals, Inc., South San Francisco, CA, USA.
⁴ The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Dharminder_Chauhan@dfci.harvard.edu.
⁵ The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Kenneth_Anderson@dfci.harvard.edu.

^# Contributed equally.

Abstract

CD73 is the key ectoenzyme involved in the generation of AMP-derived adenosine, which contributes to immunosuppression in the MM BM milieu.
Blocking CD73 activity with a potent, selective, orally bioavailable CD73 inhibitor ORIC-533 decreases adenosine generation, overcomes immune suppression, and restores immune cell-mediated MM cell lysis.
Based on these preclinical studies, a multi-center clinical trial of ORIC-533 has been initiated in patients with relapsed refractory MM (NCT05227144).