San Diego-based biotech Recludix Pharma revealed a successful Investigational New Drug (IND) application to the US FDA for REX-8756, a potent, selective oral STAT6 inhibitor, allowing the programme to advance into Phase 1 clinical testing. The drug candidate represents a potential first-in-class small-molecule approach to Type 2 inflammatory diseases including asthma.
Targeting of STAT6 opens new therapeutic axis
STAT6 (signal transducer and activator of transcription 6) is a key nodal transcription factor mediating IL-4 and IL-13 signalling pathways central to the pathophysiology of Type 2 inflammation, immune regulation, and fibrosis. Historically considered “undruggable”, recent advances have enabled the development of oral STAT6 degraders and inhibitors, with a focus on allergic and inflammatory diseases, and emerging interest in oncology.
REX-8756 directly inhibits STAT6 by binding its SH2 domain, a region critical for protein-protein interactions long deemed challenging for small-molecule drugging. In preclinical models, REX-8756 exhibited complete and sustained pathway inhibition, suppressing IL-4/IL-13-induced biomarkers and demonstrating efficacy comparable to anti-IL-4/IL-13 biologics in models of asthma, acute lung inflammation and dermatitis, with a favourable tolerability profile. The compound also has a mechanistic safety rationale: reversible target modulation without degrading STAT6 may avoid hematologic and broad immunosuppression signals associated with JAK inhibitors, offering a differentiated safety profile.
Preclinical research and platform innovation
The REX-8756 programme builds on Recludix’s proprietary SH2-focused discovery platform, which integrates custom DNA-encoded libraries and parallel structure-activity screening to tackle challenging intracellular targets with high biochemical and cellular selectivity. Preclinical data presented at scientific forums have shown selective STAT6 inhibition yields robust reduction of airway inflammation and downstream signalling biomarkers, supporting the translational rationale.
In earlier research disclosures, REX-8756 achieved complete and durable STAT6 inhibition in vitro and in vivo without degrading the protein and disrupted production of inflammatory biomarkers in multiple disease models — positioning it as a candidate for oral therapy with biologic-like efficacy.
Under a strategic partnership with Sanofi, which holds global rights beyond IND-enabling development, Recludix retains the option to share U.S. profit and loss on the programme and plans to initiate Phase 1 studies in healthy volunteers imminently.
STAT6 inhibitors in clinical development
Kymera Therapeutics leads the clinical pipeline with KT-621, a first-in-class oral STAT6 degrader: