Recludix Pharma Advances First-in-Class Oral STAT6 Inhibitor REX-8756 for Inflammatory Diseases, Including Atopic Dermatitis

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Recludix Pharma announced today the nomination of its lead development candidate, REX-8756, an oral, reversible, and highly selective STAT6 inhibitor designed to address a wide range of type 2 inflammatory diseases, including atopic dermatitis.¹

The announcement coincides with the completion of Good Laboratory Practice (GLP) toxicology studies for the candidate, a milestone that initiated a $50 million payment under the company’s collaboration with Sanofi.

The development marks a step forward in targeting signal transducer and activator of transcription 6 (STAT6), a historically "undruggable" node in the IL-4 and IL-13 signaling pathway that drives many allergic and inflammatory diseases.²

STAT6 in Type 2 Inflammation

STAT6 is a critical transcription factor that mediates the effects of IL-4 and IL-13, 2 key cytokines in Type 2 immune responses.² Its activation leads to the transcription of downstream genes involved in inflammation, fibrosis, and immune dysregulation, all of which are implicated in diseases such as:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis
• Certain forms of chronic obstructive pulmonary disease

REX-8756: Novel Mechanism and Selective SH2 Domain Targeting

REX-8756 is designed to bind selectively to the Src Homology 2 (SH2) domain of STAT6, which plays a pivotal role in cytokine receptor signaling. Recludix has built proprietary DNA-encoded libraries and utilized custom screening assays to isolate small molecules that bind with high affinity and selectivity to STAT6's SH2 domain. Unlike protein-degrading approaches, REX-8756 inhibits STAT6 without degrading the protein.

Preclinical Efficacy in Atopic and Respiratory Disease Models

Recludix reports that REX-8756 exhibits complete STAT6 pathway inhibition in vitro and in vivo, durable target engagement without requiring continuous high plasma exposure, potent suppression of IL-4/IL-13-induced biomarkers, and efficacy in murine models of asthma, acute lung inflammation, and dermatitis.

Of particular interest to dermatology clinicians is the compound’s performance in dermatitis models, where it reduced skin inflammation and epidermal thickening.

Recludix has also completed GLP-compliant toxicology studies for REX-8756, which showed favorable tolerability. The company has not reported any evidence of hepatotoxicity, immunosuppression, or hematologic dyscrasias, though full toxicology results are pending publication.

With Investigational New Drug (IND)-enabling studies underway, Recludix plans to submit an IND application later in 2025.

References

1. Recludix Pharma announces development candidate nomination of first-in-class oral STAT6 inhibitor for inflammatory diseases and achievement of significant milestone under collaboration with Sanofi. News release. June 2, 2025. Accessed June 2, 2025. https://www.globenewswire.com/news-release/2025/06/02/3091698/0/en/Recludix-Pharma-Announces-Development-Candidate-Nomination-of-First-in-Class-Oral-STAT6-Inhibitor-for-Inflammatory-Diseases-and-Achievement-of-Significant-Milestone-Under-Collabora.html
2. Radaeva M, Ton AT, Hsing M, Ban F, Cherkasov A. Drugging the ‘undruggable’: Therapeutic targeting of protein–DNA interactions with the use of computer-aided drug discovery methods. Drug Discov Today. 2021;26(11):2660-2679. doi:10.1016/j.drudis.2021.06.011.