Nurix Announces Initial NX-1607 Phase 1 Data Presented at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) Demonstrating Targeted CBL-B Inhibition in Patients with Advanced Malignancies
- Category: Small Molecules
- Published on Thursday, 10 November 2022 16:43
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Biomarker results are a positive demonstration of target engagement for this first-in-class CBL-B inhibitor
Biomarker levels achieved with NX-1607 treatment correspond to levels associated with potent anti-tumor activity in disease models
SAN FRANCISCO, CA, USA I November 10, 2022 I Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with hematologic malignancies and solid tumors, presented initial biomarker data demonstrating successful target engagement of CBL-B in its ongoing Phase 1 clinical trial with oral dosing of NX-1607. These data are being presented at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), which is being held November 8 – 12th in Boston.
“We are particularly encouraged by these initial biomarker data from the Phase 1 trial of NX-1607 measured in patients with advanced malignancies, which demonstrate remarkable concordance with levels observed in preclinical studies that are associated with potent anti-tumor activity,” said Robert J. Brown, M.D., Nurix’s executive vice president of clinical development. “The proximal biomarker of CBL-B inhibition in activated T cells can be measured in whole blood and demonstrate dose-dependence in our clinical studies enabling us to assess target engagement in the clinic and guide our selection of an appropriate dose for further expansion of the trial.”
Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix, added, "Our multiple presentations at SITC illustrate the progress we have made in the development of our first-in-class CBL-B inhibitors. Of particular importance is the work we have done to identify, validate, and clinically implement assays of a key proximal biomarker of CBL-B inhibition which has enabled the first-in-human testing of NX-1607 and its novel mechanism of action. We look forward to providing additional clinical updates for NX-1607 in 2023.”
Summary of data presented at the SITC Annual Meeting:
Title: Initial clinical characterization of novel proximal biomarkers for NX-1607, a first-in-class oral CBL-B inhibitor, in patients with advanced malignancies
Nurix has identified and characterized novel proximal biomarkers including phosphorylated hematopoietic lineage cell-specific protein 1 (pHS1) whose levels increase when CBL-B is inhibited and can be measured in ex vivo stimulated whole blood in animals and humans indicating the ability of these cells to become activated in the presence of an antigen signal such as those found in the tumor microenvironment. pHS1 is an important downstream signal of T cell activation. Preliminary pharmacokinetics and pharmacodynamic measurement of pHS1 were used to characterize the activity of NX-1607 in a first-in-human clinical trial (NCT05107674). These data demonstrate dose-responsive target engagement as measured by increases in biomarker levels in stimulated human whole blood with NX-1607 treatment reaching levels associated with anti-tumor activity in animal models at dose level 1 (5 mg) and increasing at higher doses. Preliminary PK data suggest NX-1607 has dose-proportional exposures and a mean half-life of 6 to 8 hours at doses ranging from 5 mg to 50 mg.
Title: NX-1607, a small molecule inhibitor of the CBL-B E3 ubiquitin ligase, promotes T and NK cell activation and enhances NK-mediated ADCC in a mouse lymphoma tumor model
These studies demonstrate that in addition to enhancing T-cell activation, NX-1607 renders T cells resistant to Treg and TGF-β-mediated suppression. In addition, the data demonstrate that NX-1607 treatment augments NK cell activity both in vitro, in an antibody-dependent cellular cytotoxicity (ADCC) assay using human NK cells, and in vivo, in a xenograft mouse tumor model. In a murine xenograft model of non-Hodgkin’s lymphoma (NHL), the combination of NX-1607 and rituximab (anti-CD20 Mab) significantly enhanced tumor growth inhibition and tumor rejections when compared to single agents' activity. Importantly, the survival benefit provided by the combination of NX-1607 plus rituximab was abrogated by depletion of NK cells.
NX-1607 is an orally bioavailable inhibitor of Casitas B-lineage lymphoma proto-oncogene B (CBL-B) for immuno-oncology indications, including a range of solid tumor types. NX-1607 acts on T cells, NK cells, and dendritic cells to enhance anti-tumor immunity, and has demonstrated single-agent anti-tumor activity in multiple tumor models. Nurix is evaluating NX-1607 in an ongoing, Phase 1 dose escalation and expansion trial in adults with a variety of oncology indications at multiple clinical sites. Additional information on the clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).
About Nurix Therapeutics, Inc.
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of small molecule and cell therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer and other challenging diseases. Leveraging 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 additional information visit http://www.nurixtx.com.
SOURCE: Nurix Therapeutics