07-05-2025
Recludix Pharma Presents Preclinical Data on First-in-Class BTK SH2 Domain Inhibitor Demonstrating Powerful BTK Inhibition, Exceptional Selectivity, and Encouraging Efficacy in a Model of Chronic Spon
Recludix Pharma, Inc.
-- Bruton's tyrosine kinase (BTK) SH2 inhibitor reduced skin inflammation in a clinically-relevant model of chronic spontaneous urticaria (CSU)
-- BTK inhibition through the SH2 domain results in greater selectivity as compared to BTK tyrosine kinase inhibitors (TKIs) or degraders
SAN DIEGO, May 07, 2025 (GLOBE NEWSWIRE) -- Recludix Pharma, a leader in the discovery of inhibitors of challenging targets for inflammatory disease, today announced data will be presented at the Society for Investigative Dermatology (SID) annual meeting in San Diego, CA, from an abstract titled, 'Novel Inhibitors of the BTK SH2 Domain Selectively and Potently Block BTK Signaling and are Efficacious in Preclinical Models of Chronic Spontaneous Urticaria.' The data demonstrate that the company has identified potent BTK SH2 domain inhibitors (BTK SH2i) with durable pathway inhibition and notably high selectivity for BTK, representing an attractive therapeutic approach for B cell and mast cell-mediated inflammatory diseases.
'We have developed the first known BTK SH2 domain inhibitor, and have shown preclinically that it was effective at reducing skin inflammation in a model of CSU and has exquisite target selectivity not matched by other BTK-targeting therapies,' said Ajay Nirula, M.D. Ph.D., executive vice president and head of research and development of Recludix. 'The clinical efficacy of BTK inhibitors that target the kinase domain is often compromised by the inability to maintain deep inhibition of the BTK pathway. Additionally, TKIs and kinase degraders can induce toxicities related to off-target kinase inhibition, such as platelet dysfunction. We believe that our approach of inhibiting BTK via the SH2 domain with a small molecule prodrug can address these shortcomings and is an exciting potential treatment option for immunological diseases such as CSU and multiple sclerosis.'
The company's BTK SH2i demonstrated best-in-class selectivity for BTK far greater than even the most selective BTK TKIs. Broader off-target profiling across the kinome confirmed that while current BTK TKIs and degraders showed off-target inhibition of TEC, which is associated with platelet dysfunction, Recludix's BTK SH2i did not.
The potency of a BTK SH2i was shown across multiple preclinical assays and models. In vitro, a BTK SH2i robustly inhibited proximal SH2-dependent phosphorylation (pERK) signaling and downstream immune cell activation (B cell CD69 expression). In an in vivo model, the administration of a BTK SH2i enabled deep, durable, and dose-dependent target engagement. In an in vivo model of CSU, a dose-dependent reduction in skin inflammation was observed following a single dose of a BTK SH2i.
