Nurix Therapeutics Presents Beneficial Effects of CBL-B Inhibition on Human Tumor Infiltrating Lymphocytes at SITC Conference
DeTIL-0255 is a drug-enhanced investigational new cell therapy product candidate with potentially superior T cell properties compared to conventional TIL
Michael T. Lotze, Nurix’s chief cellular therapy officer, is awarded Lifetime Achievement award by SITC at its annual meeting
SAN FRANCISCO, Nov. 12, 2021 (GLOBE NEWSWIRE) -- Nurix Therapeutics (Nasdaq: NRIX), a biopharmaceutical company developing targeted protein modulation drugs, today announced the presentation of preclinical studies demonstrating that its CBL-B inhibitor, NX-0255, enhances the number and quality of T cells expanded from tumors for use in tumor infiltrating lymphocyte (TIL) therapy. These results will be presented by Nurix in a poster session at the Society for Immunotherapy of Cancer (SITC) conference held at the Washington Convention Center on Saturday, November 13. Nurix also congratulates Michael T. Lotze, M.D., Nurix’s chief cellular therapy officer (CCO), who will be honored at the conference with the 2021 SITC Lifetime Achievement Award.
“Throughout the history of tumor infiltrating lymphocyte therapy, certain patients with melanoma and several other solid tumor types have experienced extraordinarily durable tumor responses,” said Dr. Lotze. “With our small molecule CBL-B inhibitors, we hope to broaden and deepen such responses across a range of solid tumors using our drug-enhanced TIL therapy, DeTIL-0255.”
As a key step toward advancing DeTIL-0255 into the clinic, Nurix performed a series of experiments on human tumors to characterize the effects of CBL-B inhibition using NX-0255 on the production and quality of TIL. Tumor samples were obtained from 16 patients with ovary, colon, lung, head and neck, breast, or vulva carcinomas. Tumors from patients were cultured either in the presence of recombinant human IL-2 (rhIL-2) alone to generate TIL or in combination with NX-0255 + rhIL-2 to generate DeTIL-0255, Nurix’s cell therapy clinical candidate. Compared to TIL, DeTIL-0255 demonstrated:
- Increased T cell expansion (p<0.001);
- Reduced expression of markers associated with T cell exhaustion such as PD-1, LAG-3 and TIM-3 (p<0.05);
- Increased cytotoxicity as measured by increased perforin, granzyme B, and the degranulation marker CD107a (p<0.001);
- Increased 4-1BB, a surrogate marker of tumor reactivity (p<0.05); and
- Increased T cell receptor diversity (p<0.05)
Taken together, these findings support advancing DeTIL-0255 into human clinical trials as a potentially superior, drug-enhanced TIL product candidate.
Nurix’s cell therapy programs are headed by Dr. Lotze, whose dedication and contributions to the field of immunotherapy for cancer are to be recognized at the SITC annual meeting with the 2021 SITC Lifetime Achievement Award.
“We are extremely proud of Michael and thank SITC for recognizing his achievements in the field of immunotherapy for cancer that span many of the critical advances that have had a major impact on the field,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “Michael’s irrepressible energy and drive to benefit patients with advanced cancer have compelled him to embark on the ambitious task of combining small molecules with cell therapy to create our drug-enhanced cell therapy product candidate, DeTIL-0255, a candidate and concept we believe will bring adoptive cell therapy to the next level.”
- Conference: Society for Immunotherapy of Cancer Annual Meeting
- Title: NX-0255, a Small-Molecule CBL-B Inhibitor, Expands and Enhances Tumor-Infiltrating Lymphocytes for Use in Adoptive Cancer Immunotherapy
- Abstract number: 98
- Date: November 13, 2021
- Presenter: Sarah Whelan, Ph.D.
Nurix’s lead cell therapy candidate, DeTIL-0255, is an autologous cell therapy consisting of T cells derived from a patient’s tumor expanded in culture with NX-0255 and rhIL-2. DeTIL-0255 is designed to be a single administration autologous TIL therapy infused following non-myeloablative chemotherapy. Based on its preclinical characterization, Nurix believes DeTIL-0255 could allow a broader application of TIL therapy. Nurix is currently working to initiate a Phase 1 trial of DeTIL-0255 at multiple sites in the United States that have experience in conducting TIL and other adoptive cell therapy (ACT) trials. Nurix expects to include patients primarily with gynecological tumors who have failed standard of care. Additional information on the clinical trial can be accessed at ClinicalTrials.gov (NCT05107739).
About Michael T. Lotze, M.D.
Michael T. Lotze, M.D. has served as Nurix’s Chief Cellular Therapy Officer since June 2020. He is a leading clinician scientist with more than 30 years of experience in immunology and clinical medicine, dedicating his efforts to the advancement of translational research, particularly in immunotherapy for cancer including dendritic cell, T cell, and cytokine therapies. Dr. Lotze is the co-inventor of multiple patents in dendritic cell vaccines and antigen discovery, and tumor infiltrating lymphocyte therapy. He previously held leadership roles in the biopharmaceutical industry as the chief scientific officer of Iovance Biotherapeutics and vice president of research at GlaxoSmithKline. Prior to joining Nurix, Dr. Lotze served as professor of surgery, immunology, and bioengineering, vice chair of research within the Department of Surgery and director for Damage Associated Molecular Pattern Molecule (DAMP) Laboratories at the University of Pittsburgh Medical Center Hillman Cancer Center. He was also senior advisor for the Immune Transplant and Therapy Center within the University of Pittsburgh Medical Center Enterprises and serves as associate editor of the Journal of Immunotherapy. Over the course of his career, he has authored more than 500 publications and several books. Dr. Lotze holds an M.D. from Northwestern University and completed his postdoctoral training as a scientist at the National Cancer Institute under Dr. Steven Rosenberg.
About Nurix Therapeutics, Inc.
Nurix Therapeutics is a biopharmaceutical company focused on the discovery, development, and commercialization of small molecule 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/.
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|Jason Kantor, Ph.D.||Elizabeth Wolffe, Ph.D.|
|Nurix Therapeutics, Inc.||Wheelhouse Life Science Advisors|