Nurix Therapeutics Presents Preclinical Data from Novel IRAK4 Degrader, GS-6791, Demonstrating Potent Inhibition of IL-1 and IL-36 in Vitro and Efficacy in a Model of Dermatitis

Rhea-AI Summary

Nurix Therapeutics (Nasdaq: NRIX) presented preclinical data for GS-6791, a novel IRAK4 protein degrader, at the EADV Congress in Paris. The data demonstrates the drug's effectiveness in treating inflammatory diseases through potent IRAK4 degradation and inhibition of IL-1 and IL-36 signaling pathways.

Key findings show that GS-6791 achieved near-complete IRAK4 knockdown in human blood and keratinocytes, reduced proinflammatory cytokines, and improved barrier function in dermatitis models. The compound, developed in collaboration with Gilead Sciences, is currently in a Phase 1 clinical trial evaluating its safety and tolerability in healthy volunteers.

Positive

• None.

Negative

• Early-stage development with no human efficacy data yet
• Competitive landscape in inflammatory disease treatments

Insights

Biotechnology Research Scientist

Nurix's IRAK4 degrader shows promising preclinical efficacy against inflammatory skin conditions, advancing to human trials with partner Gilead.

Nurix Therapeutics has presented compelling preclinical data for GS-6791, its IRAK4 protein degrader developed in collaboration with Gilead Sciences. This represents a significant scientific advancement in the targeted protein degradation field, specifically addressing inflammatory pathways crucial in dermatological conditions.

What makes this molecule particularly interesting is its differentiated mechanism of action. Unlike traditional kinase inhibitors that only block IRAK4's enzymatic function, GS-6791 degrades the entire protein, eliminating both kinase and scaffolding functions. This approach could potentially yield superior efficacy by more completely shutting down inflammatory signaling cascades critical in conditions like atopic dermatitis.

The preclinical package appears robust, demonstrating: 1) near-complete IRAK4 degradation in human blood and keratinocytes, 2) potent inhibition of both IL-1 and IL-36 pathways (key inflammatory mediators in skin diseases), 3) reduction of multiple inflammatory markers in human skin models, and 4) efficacy in a mouse dermatitis model with improvements in both inflammation and skin barrier function.

The compound has already advanced to Phase 1 clinical testing following FDA IND clearance in April 2025, with Gilead leading development after exercising its license option in March 2023. The ongoing first-in-human study in healthy volunteers includes biomarker assessment in skin tissue, which should provide early signals of target engagement and biological activity before advancing to patient studies.

This milestone highlights the value of Nurix's protein degradation platform technology, demonstrating its ability to produce clinical candidates addressing difficult-to-drug targets in inflammation and autoimmunity beyond traditional oncology applications.

Data support advancement of GS-6791 into clinical testing in patients with inflammatory diseases; first-in-human Phase 1 trial in healthy volunteers is ongoing

Data are being presented at the European Academy of Dermatology and Venereology (EADV) Congress

SAN FRANCISCO, Sept. 17, 2025 (GLOBE NEWSWIRE) -- 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.
  
  

About the Nurix-Gilead collaboration

In June 2019, Gilead and Nurix entered into a global strategic collaboration to discover, develop and commercialize a pipeline of up to five innovative targeted protein degradation therapies for patients with cancer and other challenging diseases. To date, Nurix has received a total of $135 million under the terms of the agreement, and for the IRAK4 program, Nurix remains eligible for $420 million in potential clinical, regulatory, and commercial milestones payments as well as up to low double-digit tiered royalties on net sales. Nurix retains the option to co-develop and co-detail up to two programs in the United States, following completion of an applicable Phase 1 clinical trial, subject to certain restrictions. For those programs that Nurix opts in to co-develop and co-detail, the parties will split development costs as well as profits and losses 50/50 for the United States, and Nurix will be eligible to receive royalties on ex-U.S. sales and reduced milestone payments. Gilead has the right to veto up to one co-development option, in which case the option will revert back to Nurix for use on potential future licensed products.

About Nurix Therapeutics, Inc.

Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, the next frontier in innovative drug design aimed at improving treatment options for patients with cancer and inflammatory diseases. Nurix’s wholly owned, clinical stage pipeline includes degraders of Bruton’s tyrosine kinase (BTK), a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B (CBL-B), an E3 ligase that regulates activation of multiple immune cell types including T cells and NK cells. Nurix also is advancing multiple potentially first-in-class or best-in-class degraders and degrader antibody conjugates (DACs) in its preclinical pipeline. Nurix’s partnered drug discovery pipeline consists of a preclinical stage degrader of STAT6, a clinical stage degrader of IRAK4, as well as multiple additional programs under collaboration agreements with Gilead Sciences, Inc., Sanofi S.A. and Pfizer Inc., within which Nurix retains certain options for co-development, co-commercialization and profit sharing in the United States for multiple drug candidates. Powered by a fully AI-integrated discovery engine capable of tackling any protein class, and coupled with unparalleled ligase expertise, Nurix’s dedicated team has built a formidable advantage in translating the science of targeted protein degradation into clinical advancements. Nurix aims to establish degrader-based treatments at the forefront of patient care, writing medicine’s next chapter with a new script to outmatch disease. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com.

Forward-Looking Statements

This press release contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this press release, the words “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “outlook,” “plan,” “predict,” “should,” “will,” and similar expressions and their variants, as they relate to Nurix, may identify forward-looking statements. All statements that reflect Nurix’s expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements regarding: the therapeutic potential and other advantages of GS-6791, including its potential to address multiple inflammatory diseases, including atopic dermatitis; the therapeutic potential of IRAK4 degradation; the opportunity for targeted protein degradation to address complex immune signaling pathways and expand treatment possibilities for patients with inflammatory diseases; and the potential benefits of the Gilead-Nurix collaboration. Forward-looking statements reflect the parties’ current beliefs, expectations, and assumptions. Although the parties believe the expectations and assumptions reflected in such forward-looking statements are reasonable, neither party can give assurances that they will prove to be correct. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and changes in circumstances that are difficult to predict, which could cause actual activities and results to differ materially from those expressed in any forward-looking statement. Such risks and uncertainties include, but are not limited to: (i) the ability of each party to perform its obligations under the Gilead-Nurix collaboration; (ii) whether the parties will be able to successfully conduct and complete preclinical development, clinical development and commercialization of any drug candidates under the Gilead-Nurix collaboration; (iii) the unexpected emergence of adverse events or other undesirable side effects during preclinical and clinical development; (iv) whether Nurix will be able to fund development activities and achieve development goals, including those under the Nurix-Gilead collaboration; (v) risks and uncertainties relating to the timing and receipt of payments from Nurix’s collaboration partners, including milestone payments and royalties on future potential product sales; and (vi) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the fiscal quarter ended May 31, 2025, and other SEC filings. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. The statements in this press release speak only as of the date of this press release, even if subsequently made available by Nurix on its website or otherwise. Nurix disclaims any intention or obligation to update publicly any forward-looking statements, whether in response to new information, future events, or otherwise, except as required by applicable law.

Contacts:

Investors
Kris Fortner
Nurix Therapeutics, Inc.
kfortner@nurixtx.com

Elizabeth Wolffe, Ph.D.
Wheelhouse Life Science Advisors
lwolffe@wheelhouselsa.com

Media
Aljanae Reynolds
Wheelhouse Life Science Advisors
areynolds@wheelhouselsa.com

FAQ

What are the key findings from Nurix's (NRIX) GS-6791 preclinical trials?

GS-6791 achieved near-complete IRAK4 knockdown in human blood and keratinocytes, demonstrated potent inhibition of IL-1 and IL-36 signaling, and showed efficacy in reducing skin inflammation in dermatitis models.

What is the current development stage of Nurix's (NRIX) GS-6791?

GS-6791 is currently in Phase 1 clinical trials with healthy volunteers, following FDA IND clearance in April 2025, evaluating safety, tolerability, and pharmacodynamics.

How does Nurix's (NRIX) GS-6791 work differently from other treatments?

GS-6791 is designed to selectively degrade IRAK4 protein, offering a differentiated mechanism compared to traditional kinase inhibition, potentially providing better efficacy in inflammatory conditions.

What is the partnership structure between Nurix (NRIX) and Gilead for GS-6791?

Gilead exercised its option to license GS-6791 in March 2023 and is now responsible for all further development as part of their research collaboration with Nurix.

What potential diseases could Nurix's (NRIX) GS-6791 treat?

GS-6791 shows potential for treating inflammatory diseases, particularly dermatological conditions like atopic dermatitis, due to its ability to inhibit IL-1 and IL-36 signaling pathways.