U.K. regulatory authorities grant Clinical Trial Authorization with dosing of first patient anticipated in the first half of 2022

NX‑5948 crosses the blood‑brain barrier in preclinical models enabling potential dual development in oncology and autoimmune diseases of the central nervous system

NX‑5948 reduces tumor burden and extends survival in a preclinical model of primary central nervous system lymphoma

SAN FRANCISCO, CA, USA I December 12, 2021 I Nurix Therapeutics, Inc. (Nasdaq: NRIX), a biopharmaceutical company developing targeted protein modulation drugs, today announced the grant of a Clinical Trial Authorization (CTA) for NX-5948, a potent and selective degrader of Bruton’s tyrosine kinase (BTK) and the second drug candidate in Nurix’s BTK degradation program. The authorization was granted by the U.K. Medicines & Healthcare products Regulatory Agency (MHRA). In connection with the approval, Nurix will initiate a Phase 1 trial of NX-5948 in patients with relapsed and refractory B-cell malignancies at clinical sites in the United Kingdom and anticipates dosing the first patient in the first half of 2022.

“Our second BTK degrader, NX-5948, demonstrates a remarkable preclinical profile that includes potent BTK degradation in microglia of the brain as well as peripheral and central anti-tumor effects with oral dosing,” said Robert J. Brown, M.D., senior vice president of clinical development of Nurix. “We believe these favorable drug properties will translate into a differentiated profile in the clinic for not only hematologic malignancies but also immune-mediated diseases including those of the central nervous system such as multiple sclerosis.”

Nurix today also announced the presentation at the 2021 American Society of Hematology (ASH) Annual Meeting of preclinical studies of NX-5948 demonstrating:

  • Dose-dependent and complete tumor growth inhibition in a mouse peripheral lymphoma model harboring the C481S BTK ibrutinib resistance mutation
  • Tumor reduction and increased overall survival in mice with intracranial TMD8 lymphoma tumors
  • Greater than 80% degradation of BTK in CNS microglia cells and in lymphoma cells implanted in the CNS

These findings, along with previously reported studies demonstrating activity in animal models of autoimmune disease, support clinical development of NX-5948 in relapsed and refractory B-cell malignancies as well as autoimmune disease.

Presentation Details

  • Conference: American Society of Hematology Annual Meeting
  • Title: NX-5948, a Selective Degrader of BTK with Activity in Preclinical Models of Hematologic and Brain Malignancies
  • Abstract number: 2251
  • Date: December 12, 2021
  • Presenter: Daniel W. Robbins, Ph.D.

About NX-5948
NX-5948 is an investigational, orally bioavailable, small molecule degrader of BTK. Nurix anticipates dosing the first patient in a Phase 1 clinical trial of NX-5948 for relapsed and refractory B-cell malignancies in the first half of 2022. Additional information on the planned clinical trial can be accessed at ClinicalTrials.gov (NCT05131022). In addition, Nurix plans to pursue development of NX-5948 for the potential treatment of certain autoimmune diseases. NX-5948 is differentiated from Nurix’s lead BTK degrader, NX-2127, in that it crossed the blood brain barrier in preclinical models and has been designed to lack IMiD activity for potential applications in indications where sparing IMiD activity may be beneficial. 

About Nurix Therapeutics, Inc.
Nurix Therapeutics is a biopharmaceutical company focused on the discovery and development of breakthrough therapies designed to modulate cellular protein levels as a novel treatment approach for cancer and other challenging diseases. Leveraging Nurix’s extensive expertise in E3 ligases together with its 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 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 T cell activation. Nurix is headquartered in San Francisco, California. For more information, please visit http://www.nurixtx.com/.

SOURCE: Nurix Therapeutics