Nurix Therapeutics is pioneering advancements in the field of protein modulation through its innovative DELigase platform, which focuses on two primary modalities: Targeted Protein Degradation (TPD) and Targeted Protein Elevation (TPE). TPD utilizes small molecules to harness the activity of E3 ligases, a class of enzymes that facilitate the degradation of specific disease-causing proteins within cells. This approach allows for the removal of proteins that contribute to various diseases, including cancer and inflammatory conditions. In contrast, TPE involves the inhibition of E3 ligases to increase the levels of beneficial proteins that are otherwise regulated for degradation. This dual capability to either degrade or elevate protein levels distinguishes Nurix's technology and enhances its therapeutic potential.

The DELigase platform is built on a foundation of extensive E3 ligase expertise and a vast collection of DNA-encoded libraries (DEL) containing over five billion small molecules. This platform enables the identification of unique binders that can either promote the degradation of harmful proteins or inhibit the degradation of beneficial ones. By leveraging the specificity of E3 ligases, Nurix aims to develop targeted therapies that can address unmet medical needs in hematologic malignancies, solid tumors, and inflammatory diseases. The company's pipeline includes several clinical-stage drug candidates, including BTK degraders for B-cell malignancies and CBL-B inhibitors for immuno-oncology, showcasing the versatility and promise of its protein modulation technologies.

United States

Nurix Therapeutics, Inc., a biopharmaceutical company, focuses on the discovery, development, and commercialization of small molecule therapies for the treatment of cancer and immune disorders. The company develops NX-2127, an orally available Bruton’s tyrosine kinase (BTK) degrader with immunomodulatory drug (IMiD) activity for the treatment of relapsed or refractory B-cell malignancies; NX-5948, an orally bioavailable BTK degrader without IMiD activity for the treatment of relapsed or refractory B-cell malignancies; and NX-1607, an orally available Casitas B-lineage lymphoma proto-oncogene-B (CBL-B) inhibitor for immuno-oncology indications. It also develops NX-0255, a CBL-B inhibitor for ex vivo use to enhance adoptive T-cell therapy; DeTIL-0255 for tumor infiltrating lymphocytes therapy; KINASE-CTM3 to treat T cell malignancies and autoimmune diseases; and LIGASE-INH2 for immuno-oncology. In addition, the company develops programs, such as COVID-CTM1, COVID-CTM2, and COVID-CTM3 that are designed for protein degradation to SARs CoV2 targets. Nurix Therapeutics, Inc. has a strategic collaboration agreement with Gilead Sciences, Inc. for cancer and other challenging diseases patients; and Sanofi S.A. The company was formerly known as Nurix Inc. and changed its name to Nurix Therapeutics, Inc. in October 2018. Nurix Therapeutics, Inc. was incorporated in 2009 and is headquartered in San Francisco, California.

Cancer

Immune System Diseases

Nurix Therapeutics

B-cell malignancies

NX-5948 is an oral small molecule degrader of BTK. Preclinical data &nbsp;support the activity of NX-5948 in tumor models harboring either &nbsp;wild-type BTK or BTK with mutations conferring clinical resistance to &nbsp;leading FDA approved agents. Unlike NX-2127, our other BTK degrader, &nbsp;NX-5948 lacks IMiD activity and has demonstrated the ability to cross &nbsp;the blood brain barrier in animal models. NX-5948 has also demonstrated &nbsp;activity in animal models of autoimmune disease.

Bexobrutideg (NX-5948)

Solid tumor/s

NX-1607 is an oral, small molecule CBL-B inhibitor. In preclinical &nbsp;animal models of both colorectal cancer and triple negative breast &nbsp;cancer, NX-1607 demonstrates anti-tumor activity and prolongs survival. &nbsp;The combination of NX-1607 with an anti-PD-1 antibody provides &nbsp;additional benefit in animal models. The anti-tumor activity of NX-1607 &nbsp;is dependent on both CD8+ T cells and NK cells.

NX-1607

Blood cancer

Chronic lymphocytic leukemia

Diffuse large B cell lymphoma

Mantle cell lymphoma

Non-Hodgkin lymphoma

E3 ligases catalyze the transfer of ubiquitin onto a target protein. The presence of the ubiquitin tag destines the protein for destruction by the proteasome. Targeted Protein Degraders are small molecules that simultaneously bind an E3 ligase and a target protein to facilitate the transfer of ubiquitin onto that target protein thus causing its degradation. Because these molecules bind two different proteins simultaneously, we refer to them as Chimeric Targeting Molecules (CTMs). The structure of the CTM has three distinct regions: the E3 ligase binder (harness), the target protein binder (hook), and the linker.
 
We have developed a series of CTMs that are potent degraders of the &nbsp;BTK protein, a genetically validated signaling factor that drives B-cell &nbsp;activation and proliferation. Our BTK degraders harness Cereblon, an E3 &nbsp;ligase which is active in hematopoietic cells, and we have designed &nbsp;CTMs to provide IMiD activity if desired. Our lead BTK CTM development &nbsp;candidate, NX-2127, is a dual degrader of both BTK and Aiolos, a protein &nbsp;target of IMiD drugs. In certain B-cell malignancy indications, we &nbsp;believe dual activity may provide therapeutic advantages that could &nbsp;result in improved outcomes.
<a href="https://www.nurixtx.com/research-development/pipeline/">Source1</a> and <a href="https://www.nurixtx.com/platform/">source 2</a>

NX-2127

NX-1607 + paclitaxel 

Waldenstrom macroglobulinemia

NX-5948 

Atopic dermatitis

Rheumatoid arthritis

GS-6791/NX-0479 is a potent, selective, oral IRAK4 degrader. IRAK4 plays a critical role in toll-like receptor (TLR) and interleukin-1 family receptor (IL-1R) signaling and has both scaffold and kinase functions, making it an ideal target for disruption by targeted protein degradation. Degradation of IRAK4 by GS-6791/NX-0479 has potential applications in the treatment of rheumatoid arthritis and other inflammatory diseases. Nurix’s collaboration partner, Gilead Sciences, licensed the program in 2023 and is responsible for advancing this program through clinical development.

GS-6791/NX-0479

Cervical cancer

Endometrial cancer

Ovarian cancer

DeTIL-0255 is a cellular therapy that incorporates our proprietary &nbsp;small molecule CBL-B inhibitor NX-0255 in the cell expansion process of &nbsp;tumor infiltrating lymphocytes (TIL). We call this drug-enhanced TIL, or &nbsp;DeTIL. While DeTIL-0255 incorporates a CBL-B inhibitor, we are also &nbsp;exploring combining other targeted agents, such as its proprietary &nbsp;protein degraders, to enhance T cell expansion and phenotypes.

Nurix Therapeutics

Company Details