Nurix Therapeutics Shares Preclinical Data on NX-5948 and GS-6791 at ACR Convergence 2024

On November 17, 2024, Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company, shared preclinical data regarding two of its pipeline programs, NX-5948 and GS-6791. The data, which pertain to the mechanisms of action and disease models, were presented at the ACR Convergence 2024, the annual meeting of the American College of Rheumatology held in Washington, D.C.

NX-5948 is Nurix's proprietary, orally available Bruton’s tyrosine kinase (BTK) degrader. This drug is being developed for the treatment of inflammation, autoimmune diseases, and is currently in a Phase 1b trial for B-cell malignancies. GS-6791, on the other hand, is a selective, orally bioavailable degrader of interleukin-1 receptor-associated kinase 4 (IRAK4). This drug is being developed in collaboration with Gilead Sciences to potentially treat rheumatoid arthritis and other inflammatory diseases.

Arthur T. Sands, M.D., Ph.D., the president and CEO of Nurix, highlighted the significance of the data presented, emphasizing the potential of Nurix's targeted protein degradation strategy over kinase inhibition for tackling inflammatory and autoimmune diseases. He pointed out that these findings support the continued progress of these drug candidates into clinical studies, showcasing the efficacy of Nurix’s DELigase platform in generating superior degrader drug candidates.

BTK plays a crucial role in signaling downstream of the B cell receptor (BCR), toll-like receptors (TLRs), and Fc receptors (FcRs). This makes BTK a promising therapeutic target in antibody-mediated autoimmune and inflammatory diseases. The data presented in the poster titled "NX-5948, a Clinical-Stage BTK Degrader, Achieves Deep Suppression of BCR, TLR, and FcR Signaling in Immune Cells and Demonstrates Efficacy in Preclinical Models of Arthritis and Other Inflammatory Diseases" demonstrated that NX-5948 could achieve superior or equivalent results compared to BTK inhibition across various mechanistic studies and models of inflammatory diseases. In primary B cells, NX-5948 promoted rapid degradation of BTK and more potently suppressed BCR signaling and BCR- and TLR-mediated B cell activation than current BTK inhibitors. Additionally, in a model of established collagen-induced arthritis, oral administration of NX-5948 resulted in equal or superior clinical improvement and deeper suppression of plasma cell numbers compared to BTK inhibitors. NX-5948 also showed efficacy in other models of inflammatory diseases, including antibody-induced glomerulonephritis, autoimmune lymphoproliferative syndrome, passive cutaneous anaphylaxis, and experimental autoimmune encephalitis.

Similarly, IRAK4 is integral to TLR- and interleukin-1 receptor-mediated signaling, which induces inflammatory responses. GS-6791, a targeted protein degrader of IRAK4, offers a differentiated mode of action compared to kinase inhibitors. The poster titled "IRAK4 Degrader GS-6791 Inhibits TLR and IL-1R-Driven Inflammatory Signaling, and Ameliorates Disease in a Preclinical Arthritis Model" highlighted that GS-6791 is a potent degrader of IRAK4 both in vitro and in vivo. The data showed that GS-6791 inhibited IL-1 and TLR-induced cytokine release and provided a deeper reduction of cytokine responses in human B cells and synovial fibroblasts compared to IRAK4 kinase inhibitors. Additionally, in a preclinical model of arthritis, orally administered GS-6791 demonstrated significant, dose-dependent efficacy.

Nurix Therapeutics is a biopharmaceutical company specializing in the development of innovative small molecules and antibody therapies to modulate cellular protein levels. The company is focused on treating cancer, inflammatory conditions, and other challenging diseases using its proprietary DELigase platform. This platform helps in identifying and advancing novel drug candidates by targeting E3 ligases, a class of enzymes central to the modulation of cellular proteins. Nurix’s clinical-stage pipeline includes targeted protein degraders of BTK and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, which regulate immune cell activation. The company is headquartered in San Francisco, California.