Recently, Recludix Pharma released a major news, nominating its main development candidate drug REX-8756. This is an oral, reversible and highly selective STAT6 inhibitor, aiming to overcome various type 2 inflammatory diseases including atopic dermatitis. Once this news was announced, it attracted widespread attention in the medical field and also marked an important step in the research on the treatment of type 2 inflammatory diseases.
Key point: GLP toxicology studies completed attract much attention from all parties
This announcement comes at a time when REX-8756 has successfully completed the GLP toxicology studies, a milestone achievement of great significance. With this result, Recludix Pharma triggered the key terms of the collaboration agreement with Sanofi and successfully received a payment of 50 million US dollars. The completion of the GLP toxicology studies is not only an important interim achievement in the safety assessment of REX-8756, but also lays a solid foundation for the subsequent clinical research and development of the drug, and demonstrates the stable progress of the drug in the research process.
Target breakthrough: Directly hitting the “undruggable” target STAT6
The development of REX-8756 focuses on the signal transducer and activator of transcription 6 (STAT6), a target that plays a key role in the IL-4 and IL-13 signaling pathways. For a long time, STAT6 has been regarded as a “undruggable” node, but it plays a core role in driving numerous allergic and inflammatory diseases. As a key transcription factor in the type 2 immune response, STAT6 can mediate the effects of IL-4 and IL-13, and its activation will trigger a series of downstream gene transcription, leading to inflammation, fibrosis, and immune dysregulation, and is closely related to the occurrence and development of various diseases such as atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and certain types of chronic obstructive pulmonary disease. The emergence of REX-8756 is expected to break this deadlock and bring new possibilities for the treatment of related diseases.
Innovative mechanism: Highly selective targeting of the SH2 domain
The mechanism of action of REX-8756 is highly innovative. It aims to selectively bind to the Src homology 2 (SH2) domain of STAT6, which plays a crucial role in cytokine receptor signal transduction. Recludix Pharma successfully isolated small molecules that can bind to the SH2 domain of STAT6 with high affinity and selectivity by constructing a proprietary DNA encoding library and using customized screening analysis techniques. Unlike common protein degradation methods, REX-8756 can effectively inhibit STAT6 without degrading the protein, providing a new idea and direction for drug development.
Preclinical validation: Excellent efficacy demonstrated in multiple models
During the preclinical research stage, REX-8756 showed an inspiring performance. The data released by Recludix Pharma demonstrated that the drug could achieve complete inhibition of the STAT6 pathway both in vitro and in vivo, with persistent target engagement ability, and no need for continuous maintenance of high plasma exposure levels. At the same time, it could effectively inhibit IL-4/IL-13-induced biomarkers. In various mouse model experiments for asthma, acute pulmonary inflammation, and dermatitis, REX-8756 demonstrated excellent efficacy. In particular, it is worth noting that in the dermatitis model, this compound could significantly reduce skin inflammation and epidermal thickening, which undoubtedly fills dermatologists with anticipation. In addition, the completed GLP toxicology studies also showed that REX-8756 has good tolerance and no evidence of liver toxicity, immunosuppression, or hematological malignancy has been found so far, although the complete toxicology results are still pending, the existing data is sufficient to give confidence in its safety.
Future outlook: IND application progresses steadily With the orderly progress of the research and development work of investigational new drugs (IND), Recludix Pharma plans to submit the IND application later in 2025. If the application is successfully approved, REX-8756 will officially enter the clinical trial stage and undergo more rigorous testing. This is not only an important moment in Recludix Pharma’s research and development journey, but also brings new hope to many patients suffering from type 2 inflammatory diseases. In the future, whether REX-8756 can continue its excellent performance in preclinical research during the clinical trials and provide safer and more effective treatment options for patients, is something that both the industry and patients are eagerly awaiting.
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