Nurix And Gilead Advance IRAK4 Degrader GS-6791 Into Clinical Trials After Preclinical Results In Skin Disease

Author: Benzinga Newsdesk | September 17, 2025 06:10am

Nurix Therapeutics, Inc. (NASDAQ:NRIX) today announced the presentation of preclinical data from GS-6791/NX-0479, a novel IRAK4 protein degrader discovered as part of the company's ongoing research collaboration with Gilead Sciences. The findings support advancement of GS-6791 into clinical studies and are being presented at the European Academy of Dermatology and Venereology (EADV) Congress, taking place September 17–20, 2025, in Paris, France.

The data show that GS-6791 mediates sustained degradation of IRAK4, resulting in robust inhibition of IL-1- and IL-36-driven responses in skin epithelial cell systems and significant disease reduction in a preclinical model of atopic dermatitis (AD).

"As a potent, orally available degrader of the IRAK4 kinase, GS-6791 has a differentiated pharmacologic profile, providing an alternative method to target IRAK4 pathway with the potential to deliver efficacy in multiple inflammatory indications," said Gwenn M. Hansen, Ph.D., chief scientific officer at Nurix. "These findings underscore the opportunity for targeted protein degradation to address complex immune signaling pathways and expand treatment possibilities for patients with inflammatory diseases."

"Our collaboration with Gilead has been highly productive, and we are excited to see the first program from this partnership advance into the clinic," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "These results highlight the potential of IRAK4 degradation as a novel approach for treating inflammation and autoimmune diseases and reinforce our shared commitment to developing innovative therapies that can improve outcomes for patients."

GS-6791 is designed to selectively degrade IRAK4, a signaling protein with both kinase and scaffold functions that plays a central role in toll-like receptor (TLR) and interleukin-1 family receptor (IL-1R) pathways. By degrading IRAK4, GS-6791 offers a differentiated mechanism of action compared to kinase inhibition alone.

Preclinical data presented at EADV demonstrate that GS-6791 is a potent, selective, oral IRAK4 degrader with activity across immune and epithelial systems relevant to dermatologic disease:

• Potent IRAK4 degradation: Achieved near-complete knockdown in human blood and keratinocytes.
• Deep cytokine pathway inhibition: Potency against IL-1 and IL-36 signaling.
• Dermatology relevance: Reduced proinflammatory cytokines (IL-8, CXCL1, TSLP, IP-10) and disease-associated gene expression (DEFB4B, S100 family) in keratinocytes and 3D reconstructed human epidermis.
• In vivo efficacy: Suppressed cytokines in an IL-1β challenge model; reduced skin inflammation and improved barrier function in a mouse dermatitis model.
• Gilead exercised its option to license GS-6791 in March 2023, after which Gilead became responsible for all further development. The Investigational New Drug (IND) application for GS-6791 was cleared by the U.S. Food and Drug Administration (FDA) in April 2025. The ongoing Phase 1 clinical trial is evaluating the safety, tolerability, and pharmacodynamics of GS-6791 following single and multiple doses in healthy volunteers, including biomarker assessment in the skin.
   

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