Executives from Nurix Therapeutics (NASDAQ:NRIX) used a recent discussion on the company’s immunology and inflammation (I&I) efforts to outline why the firm believes targeted protein degradation could offer advantages over conventional small-molecule inhibition in inflammatory diseases. While Nurix is often associated with its oncology programs, company leadership argued its I&I pipeline—centered on BTK, IRAK4, and STAT6—has been “somewhat overlooked” despite being, in their view, “very robust.”
Why Nurix says degraders can outperform inhibitors in I&I
The company emphasized two primary advantages of degraders versus inhibitors. First, degraders remove the entire target protein, not just its enzymatic activity. For kinase targets such as BTK and IRAK4, Nurix said this matters because these proteins can signal not only through their catalytic activity but also through non-enzymatic “scaffolding” functions that inhibitors may not fully address.
Second, Nurix highlighted the ability of degraders to target proteins that are traditionally difficult for small molecules to inhibit. As an example, the company described STAT6—a transcription factor—as lacking a traditional enzyme active site, making it challenging for classical inhibitor approaches. With a degrader, Nurix said it only needs to bind somewhere on the protein to trigger degradation via the ubiquitin-proteasome system.
STAT6 program NX-3911: partnership with Sanofi and selectivity data
Nurix discussed its STAT6 degrader program, NX-3911, which is partnered with Sanofi. According to the discussion, Sanofi took control of IND-enabling studies after extending its option last year, and is expected to file an IND this year. Nurix said it does not have additional visibility into specific gating items or timing beyond “industry standard” expectations, and noted that announcements about program progression will be Sanofi’s responsibility.
Nurix framed STAT6 degradation as aiming to mimic a gene knockout phenotype, calling STAT6 knockout a “great phenotype” in animals: healthy overall, but lacking IL-4/IL-13 signaling and therefore lacking a type 2 inflammatory response while maintaining otherwise intact immune systems.
On binding details, the company said it has not disclosed where NX-3911 binds on STAT6. Nurix attributed discovery of the STAT6 ligand to its proprietary DNA-encoded library (DEL) approach, describing it as a 5 billion compound library that can probe protein surfaces broadly.
On selectivity, Nurix said that in high-resolution global proteomics experiments in normal human immune cells, STAT6 was the only protein degraded at clinically relevant concentrations, and other STAT family members did not shift. The company said these proteomics data have been shared previously in company materials.
Regarding kinetics and permeability, Nurix said STAT6 degradation in cells occurs “within minutes,” including in stimulated and unstimulated settings, which it presented as evidence of cell permeability. It also described oral dosing studies in multiple animal species “through primates,” saying it observed rapid, potent, and complete STAT6 degradation. In disclosed mouse models of type 2 inflammation, Nurix said STAT6 levels fell rapidly and inflammatory responses were reduced substantially, describing effects that moved inflammatory markers below knockout levels and below unchallenged mice in those models.
Positioning versus established therapies and the broader STAT6 market
Nurix did not offer a direct head-to-head comparison against Kymera’s STAT6 program, noting it did not have Kymera’s molecule. It said its comparisons in animal models were made against “industry benchmarks of approved agents” that block the pathway, and that NX-3911 performed “extremely well” in those benchmarks. The company also noted that the program is oral, which it characterized as an advantage.
When asked about positioning in a landscape shaped by dupilumab, Nurix argued the opportunity for an oral, safe agent with a profile comparable to injectable biologics is large and could reach “tens of millions of patients” who may prefer not to use an injectable. The company suggested there is room for multiple drugs across the variety of type 2 inflammatory diseases and segments.
BTK degrader bexobrutideg: autoimmune focus and tablet formulation
Nurix also addressed its BTK degrader, bexobrutideg, which it said has been developed in hematologic malignancies and is also being advanced for I&I use cases. The company discussed an exploratory look at warm autoimmune hemolytic anemia (wAIHA) in a small number of chronic lymphocytic leukemia (CLL) patients who had wAIHA concurrently, describing it as an early proof-of-concept effort rather than a primary commercial indication.
Nurix noted that, since that cohort began, BTK inhibitor data in autoimmune hematology indications such as wAIHA and ITP have expanded and shown strong results, which it said establishes proof of concept for the mechanism. The remaining question, in the company’s view, is whether a degrader can be better. It also cited other areas of interest for BTK modulation, including dermatology—referencing approval of remibrutinib in chronic spontaneous urticaria (CSU)—and neurology, referencing recent positive multiple sclerosis (MS) results for venetoclax from Roche.
For broader I&I indications such as CSU or MS, Nurix said it is developing a tablet formulation of bexobrutideg. The company reported the tablet is being studied in healthy volunteers and is currently in the multiple ascending dose (MAD) portion of the Phase 1 work. It suggested a tablet could enable a wider range of lower doses that may be useful in I&I, and could offer a different product profile than the oncology capsule, providing development and commercial flexibility. Nurix said its goal is to report Phase 1 data this year, but declined to specify what pharmacodynamic or ex vivo assay data might be included.
IRAK4 degrader with Gilead: tissue penetration and safety considerations
Nurix’s third I&I pillar discussed was IRAK4, partnered with Gilead. The company described IRAK4 as another key kinase node and said the program was launched under a 2019 collaboration. According to Nurix, Gilead previously had an IRAK4 inhibitor in the clinic and saw limitations that, in the company’s telling, supported the rationale for degradation rather than inhibition. Nurix said it compared its degrader to Gilead inhibitors during development to demonstrate superiority in vitro. The company stated the IRAK4 degrader is completing the MAD portion of healthy volunteer studies under Gilead’s administration.
Asked about lessons from another IRAK4 degrader program (Sanofi/Kymera’s KT-474), Nurix said it was able to make and profile that molecule against its own candidate. Nurix said it observed significantly better tissue penetration with its candidate—particularly in skin—reporting near-total IRAK4 degradation in skin compared with about 50% levels for the comparator. The company also cited QT-related safety issues it associated with the other program, and said it has not seen those issues, describing extensive animal cardiac safety work on its own clinical candidate. Nurix emphasized that, like small molecules, “not all degraders are created equal,” and said success depends on optimizing multiple parameters.
The company concluded by signaling expectations that its immunology pipeline could become a more prominent part of its story, characterizing 2026 as a potentially significant year for its I&I programs.
About Nurix Therapeutics (NASDAQ:NRIX)
Nurix Therapeutics, Inc is a clinical-stage biopharmaceutical company focused on the discovery and development of small-molecule therapies that harness the ubiquitin-proteasome system to selectively degrade disease-causing proteins. By modulating E3 ubiquitin ligases and related molecular machinery, Nurix aims to expand treatment options for patient populations with unmet medical needs in oncology and immunology.
The company’s pipeline includes multiple programs in various stages of development.
