Nurix Presents the Discovery and Chemical Structure of First-in-Class CBL-B Inhibitor NX-1607 at the American Chemical Society (ACS) Meeting
Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, today 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.
“Today’s presentation at the ACS meeting showcases Nurix’s innovative combination of structure-based-drug-design and industry-leading expertise in the biochemistry of E3 ligases,” noted Gwenn Hansen, Ph.D., Nurix’s chief scientific officer. “Our unique approach to drug discovery enables us to design novel drugs that either inhibit E3 ligases, such as NX-1607, or harness E3 ligases for targeted protein degradation.”
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. A copy of the presentation is available on the Posters and Presentations section of the scientific resources page of Nurix’s website.
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. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).
CBL-B is an E3 ubiquitin ligase expressed in immune cells that regulates T-cell activation. CBL-B inhibition reduces T-cell exhaustion and increases cytokine production upon T cell receptor stimulation, overcoming suppressive signals in the tumor microenvironment. Furthermore, lack of CBL-B allows T-cell activation despite low target antigen expression on tumor cells, potentially reversing the tumor escape mechanism of resistance. Nurix is pursuing inhibition of CBL-B as a means to increase anti-tumor immune responses and potentially improve outcomes in patients with solid tumors and hematologic malignancies.
March 22, 2024
