Elizabeth Gagea, Emma Lee
Background
Nurix is a biotechnology company headquartered in San Francisco, California, focused on advancing the cancer immunotherapeutic industry. The company works to develop drugs that regulate E3 ligases using their DEligase platform. They developed DEL (DNA encoded library) with more than five billion molecules, each containing a unique barcode that allows for trace amounts of the given molecule to be identified using sequencing technology. Through the DNA library, Nurix can perform targeted protein modulation, identifying molecules that affect protein levels.Specifically, Nurix’s DNA-encoded libraries are designed to determine target proteins and unique binders which affect E3 ligases, which are responsible for promoting protein (ubiquitination) synthesis and degradation. DELigase can be harnessed to modulate protein levels through Targeted Protein Degradation or Targeted Protein Elevation. Targeted Protein Degradation alters the function of E3 ligases to degrade disease causing proteins while Targeted Protein Elevation increases beneficial proteins by inhibiting E3 ligase from degrading beneficial proteins.
Nurix works with partners, Gilead and Sanofi, to leverage targeted protein modulation to advance drug discovery against solid tumors and blood cancer. They’re currently working on drug discovery and clinical trials in areas of hematology-oncology, immuno-oncology, and inflammation. For example in the area of Hematology-Oncology, Nurix is woking on developing BTK (Bruton’s Tyrosine Kinase) degraders to hopefully generate superior outcomes for patients whose tumors have acquired resistance to current inhibitor based therapies through mutations in the BTK protein, which regulates B-cell malignant proliferation. Furthermore, in the area of Immuno-oncology, Nurix is targeting Casitas B-lineage lymphoma proto-oncogene-b (CBL-B), expressed in cancer, which is an E3 ligase that negatively regulates the immune system (T-cell and NK cell activation). Nurix has developed two ligase inhibitors of CBL-B, NX-1607 and NX-0255, both of which are in clinical trials, which prevent the degradation of T-cells, allowing the immune system to produce tumor suppressing proteins. IRAK4 is a serine/tyrosine kinase that plays a significant role in inflammation and oncology. Nurix is developing two IRAK4 degraders (NX-0479 / GS-6791), using their Protein Degradation technology to eliminate IRAK4’s activity that can only be suppressed by eliminating its enzymatic and scaffolding activity, which produces anti-inflammatory effects.
Comments