STAT6
Global Partnership for STAT6 Inhibitor
Recludix and Sanofi have established a strategic partnership to develop and commercialize first-in-class oral small molecule STAT6 (signal transducer and activator of transcription 6) inhibitors for patients with immunological and inflammatory diseases. STAT6 is believed to play a key role in multiple dermatological and respiratory diseases.
STAT6 in Inflammatory Disease
Allergic diseases are commonly driven by T helper type 2 (Th2) inflammation, with IL-4 / IL-13 representing two of the most important cytokines driving disease.
By blocking IL-4 and IL-13 binding, treatment with monoclonal antibodies has delivered transformative efficacy across both common and rare diseases, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. However, these large molecules require regular injections, are typically restricted to certain patient subsets, and can provoke immunogenicity.
Oral, reversible inhibitors of the Janus Kinase (JAK) family, have been approved as treatments for Th2-mediated atopic dermatitis. However, JAK inhibition can negatively impact anti-viral immunity and hematopoiesis, leading to safety concerns.
Beyond inflammation, blocking the IL-4/IL-13 pathway also rapidly improves severe itch which is a key symptom impacting the quality of life of patients with dermatitis and prurigo nodularis, and inhibitors of IL-4 and IL-13 signaling are highly effective in these Th2-driven diseases.
STAT6 is required for IL-4 and IL-13 signaling, but it is downstream in the JAK/STAT pathway and is not utilized by other cytokines and growth factors. Therefore, a selective STAT6 inhibitor is predicted to be more targeted with fewer side effects and represents a unique and valuable drug target. Recludix’s approach to inhibiting STAT6 with oral, selective, reversible, small molecule drugs is a differentiated alternative to the injectable biologics and JAK family kinase inhibitors for the treatment of Th2-driven inflammatory diseases.
STAT6 in Cancer
Recurring, activating hotspot mutations are found in STAT6 across B-cell lymphomas, including diffuse large B-cell lymphoma, Hodgkin lymphoma, and follicular lymphoma. Approximately 5 to 30% of patients with these diseases harbor STAT6 mutations.
STAT6 mutations in B-cell lymphomas are largely mutually exclusive with other known oncogenic mutations, strongly suggesting that STAT6 mutations are oncogenic drivers. Tumors with these mutations therefore are likely to be sensitive to STAT6 inhibition.