Recludix's Oral STAT6 Inhibitor REX-8756 Shows Efficacy Comparable to Monoclonal Antibodies in Atopic Dermatitis Model
核心洞察
Recludix Pharma (搜索)'s oral STAT6 inhibitor REX-8756 (搜索) demonstrated efficacy comparable to monoclonal antibodies targeting IL-4 (搜索)/IL-13 (搜索) signaling pathways in a preclinical atopic dermatitis (搜索) model.
The drug showed a differentiated safety profile compared to JAK inhibitors, avoiding impairment of growth factor signaling critical for hematologic homeostasis and broad immunosuppression.
REX-8756 (搜索) represents the first known orthosteric STAT6 SH2 domain inhibitor to enter clinical trials, currently being evaluated in an ongoing Phase 1 study.
Recludix Pharma (搜索) has announced promising preclinical data for its oral STAT6 inhibitor REX-8756 (搜索), demonstrating efficacy comparable to monoclonal antibodies in treating atopic dermatitis (搜索) while offering a differentiated safety profile. The data was presented at the Society for Investigative Dermatology (SID) Annual Meeting in May 2026.
Preclinical Efficacy Matches Biologics
In a Th2-mediated model of atopic dermatitis (搜索), oral administration of REX-8756 (搜索) to mice successfully attenuated skin inflammation with efficacy comparable to monoclonal antibodies targeting IL-4 (搜索)/IL-13 (搜索) signaling pathways. The preclinical efficacy was associated with reductions of Th2 cytokines, specifically IL-13 and IL-5 (搜索), within the immune compartment.
"This data set adds to a growing body of evidence across disease models showing that selective and complete inhibition of STAT6 with REX-8756 (搜索) is comparable to biologics while enabling oral dosing and avoiding the broader safety risks of JAK inhibition," said Ajay Nirula, M.D., Ph.D., president and head of R&D at Recludix.
Differentiated Safety Profile
Unlike Janus Kinase (JAK) inhibitors, REX-8756 (搜索) does not impair growth factor signaling critical for hematologic homeostasis and is not broadly immunosuppressive. This safety advantage positions the compound as a potentially safer alternative to existing oral treatments for inflammatory diseases.
First-in-Class Mechanism
REX-8756 (搜索) represents the first known orthosteric STAT6 SH2 domain inhibitor to enter clinical trials. According to Nirula, this is an important distinction from both allosteric inhibitors and protein degraders, as REX-8756 binds the active site to directly block physiological protein function, enabling selective, potent, durable, and reversible inhibition.
Clinical Development and Partnership
The compound is currently being evaluated in an ongoing, placebo-controlled Phase 1 study involving approximately 100 healthy volunteers across multiple cohorts. The study aims to clinically evaluate REX-8756 (搜索)'s safety, tolerability, pharmacokinetics, and pharmacodynamics.
Recludix is conducting the Phase 1 study of REX-8756 (搜索) (also known as SAR448755 (搜索)) through a strategic development and commercialization partnership with Sanofi, where Recludix has the option to participate in an equal U.S. profit/loss share.
Targeting Type 2 Inflammatory Diseases
STAT6 is a key nodal transcription factor that selectively mediates downstream signaling of IL-4 (搜索) and IL-13 (搜索), dominant and central cytokines in the pathophysiology of Type 2 inflammatory diseases. Abnormal activation of STAT6 is found in inflammatory diseases, such as atopic dermatitis (搜索), asthma (搜索), chronic obstructive pulmonary disease (搜索) and chronic spontaneous urticaria (搜索).
A STAT6 inhibitor offers the potential for a novel, first-in-class, targeted oral therapy for patients in the treatment of Type 2 inflammatory diseases, potentially providing an oral alternative to injectable biologics currently used in these conditions.