Presentation highlights Nurix’s innovation and leadership in targeted protein modulation, including ligase inhibition

Unique mechanism of action, an intramolecular glue, locks the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) in a closed inactive state

Phase 1 trial ongoing as monotherapy and in combination with paclitaxel in patients with a range of oncology indications

SAN FRANCISCO, CA, USA I March 20, 2024 I 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 (NCT05107674).

About CBL-B
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.

About Nurix Therapeutics, Inc.
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions, and other challenging diseases. Leveraging extensive expertise in E3 ligases together with proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform, to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates activation of multiple immune cell types including T cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit

SOURCE: Nurix Therapeutics