Recludix Pharma Showcases Oral STAT3 Inhibitors' Efficacy and Safety in Th17 Skin Inflammation at SID Annual Meeting

Recludix Pharma, Inc., a prominent player in the field of drug discovery for treating inflammatory diseases and cancer, presented promising new data at the Society for Investigative Dermatology (SID) Annual Meeting in San Diego. The presentation, led by Paul Smith, Ph.D., Senior Vice President of Biology at Recludix, focused on the efficacy and safety of their orally bioavailable STAT3 inhibitors in preclinical models of Th17-mediated skin inflammation. The study particularly highlighted the potential of REX-7117, a selective small molecule STAT3 inhibitor, to offer significant therapeutic benefits for diseases such as psoriasis, with efficacy comparable to anti-IL-17A biologics.

STAT3 inhibitors like REX-7117 have shown deep, durable inhibition of the STAT3 pathway, which is critical for the development and function of Th17 cells, known for their role in inflammatory diseases. Unlike other inhibitors such as JAK1/2 and TYK2, REX-7117 does not impair broader immune responses, including antiviral immunity and growth factor signaling essential for hematologic health. This selectivity potentially translates to fewer side effects, making it a safer option compared to existing treatments.

Ajay Nirula, M.D., Ph.D., Executive Vice President and Head of Research and Development at Recludix, emphasized the significance of these findings. He noted that oral STAT3 inhibitors like REX-7117 could replicate the potent efficacy of biologics but with the convenience of oral administration. This high selectivity might also mitigate some safety issues associated with current JAK and TYK2 inhibitors. Nirula suggested that STAT3 inhibition could be an effective treatment strategy for a variety of Th17- and Th1-mediated conditions, including psoriasis, psoriatic arthritis, rheumatoid arthritis, and inflammatory bowel disease.

REX-7117 and its counterpart REX-5376 have demonstrated high potency and selectivity in various biochemical and cellular assays. They have the potential to disrupt inflammatory Th17 cell function without affecting other critical cytokine pathways. This includes maintaining STAT1-mediated signaling, which is important for antiviral defense, unlike the adverse impacts seen with baricitinib (JAK1/2) and deucravacitinib (TYK2). Furthermore, REX-7117 does not impair either type I or type II interferon-mediated antiviral activity, crucial for combating viral infections, nor does it affect STAT5-mediated signaling by hematopoietic growth factors, thereby reducing risks like anemia and thrombocytopenia common with some JAK inhibitors.

In preclinical models, particularly a murine IL-23 induced psoriasis model, REX-7117 exhibited efficacy on par with an anti-IL-17A antibody surrogate treatment and outperformed clinically relevant doses of deucravacitinib. This positions REX-7117 as a strong candidate for further development in treating inflammatory skin conditions.

STAT3, a critical signaling molecule, is activated by cytokines such as IL-23 and IL-6, which are involved in the generation and function of pathogenic Th17 cells. These cells play a significant role in various inflammatory diseases, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. The inhibition of STAT3 offers potential therapeutic benefits beyond Th17/IL-17 driven diseases, extending to conditions where IL-6 pathway blockade is validated. Clinical trials targeting other STAT3 dependent cytokines like oncostatin M (OSM) and IL-22 have shown efficacy in inflammatory diseases, underscoring the broad potential of STAT3 inhibitors.

Recludix Pharma, leveraging its unique drug discovery platform, is at the forefront of developing potent and selective inhibitors for challenging protein targets. Their innovative approach integrates custom DNA-encoded libraries and proprietary screening tools to ensure selectivity and effectiveness. With a strategic partnership with Sanofi and a focus on STAT proteins, Recludix is advancing its STAT3 inhibitors for various inflammatory and oncological indications, promising new treatment avenues for patients suffering from these complex conditions.