Nurix Therapeutics, Inc. disclosed the discovery and structure of NX-1607 in the First Time Disclosures session at the American Chemical Society Spring 2024 meeting in New Orleans, LA. This is the first inhibitor of CBL-B to advance into clinical studies and a prime example of Nurix?s ability to target previously undruggable E3 ligases. In an oral presentation at the American Chemical Society Spring meeting entitled NX-1607: a First-In-Class Inhibitor of Casitas B-lineage Lymphoma B (CBL-B) for Immuno-Oncology, Nurix disclosed the structure of NX-1607 and its discovery history.

NX-1607 acts as a specific intramolecular glue of the CBL-B protein, locking it in a closed and inactive conformation that lowers the threshold for T-cell activation. This mechanism of action is notable because CBL-B lacks a classic enzymatic active site binding pocket, preventing typical inhibitor design and thereby requiring a novel drug discovery approach. Nurix is testing NX-1607 in an ongoing, first-in-human, multicenter, open-label, Phase 1a/1b dose-escalation/expansion trial to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and preliminary anti-tumor activity of NX-1607 in patients with advanced malignancies, including solid tumors and lymphoma.

The trial includes both a monotherapy and a combination cohort utilizing paclitaxel. In 2024, Nurix expects to present data from the Phase 1a dose-escalation portion of the trial of NX-1607 and to define dose(s) to enable Phase 1b cohort expansion.