Science Signaling Article Shows Soquelitinib's Potential for ITK Inhibition in Treating Inflammatory Diseases

1 August 2024

Recent research by Cornell University, published in the journal Science Signaling, has highlighted the potential of ITK inhibition as a promising treatment approach for inflammatory diseases. This study utilized soquelitinib, a selective ITK inhibitor developed by Corvus Pharmaceuticals, to demonstrate its effects both in vitro and in vivo. The findings indicate that ITK inhibition can switch proinflammatory Th17 cells into anti-inflammatory Treg suppressor cells.

The research, led by Avery August, Ph.D., Professor of Immunology at Cornell's College of Veterinary Medicine, provides deeper insights into how ITK regulates the balance between Th17 and Treg cells. Dr. August’s team focuses on understanding the role of tyrosine kinases in immune response regulation and T cell differentiation. Their research reveals that soquelitinib can significantly impact inflammatory and autoimmune diseases by modulating these cell types.

James Rosenbaum, M.D., senior vice president of research at Corvus, emphasized the importance of this study, noting that it confirms the broad therapeutic potential of ITK inhibition. According to Rosenbaum, the dual effect of decreasing Th17 cells while increasing Treg cells is particularly relevant for treating autoimmune, allergic, and inflammatory conditions. This was demonstrated in an asthma model where soquelitinib reduced lung inflammation by altering the Th17/Treg cell ratio.

The article, titled “The kinase ITK controls a Ca2+-mediated switch that balances Th17 and Treg cell differentiation,” details several key findings from preclinical studies. In vitro experiments showed that ITK inhibition with soquelitinib leads to a dose-dependent reduction in Th17 cell differentiation and an increase in Foxp3+ Treg cells. In vivo studies further confirmed these findings, demonstrating that soquelitinib treatment in mice with allergic airway inflammation reduced Th17 cells and increased Treg cells in the lungs.

Corvus Pharmaceuticals, a clinical-stage biopharmaceutical company, is pioneering the development of ITK inhibitors, with soquelitinib being their lead product candidate. The company is also working on several next-generation ITK inhibitors for various inflammatory and immune diseases. Soquelitinib is currently undergoing clinical trials for both oncology and immunology indications.

Soquelitinib, formerly known as CPI-818, is an investigational oral drug designed to selectively inhibit ITK, an enzyme crucial for T cell and NK cell functions. Interim results from a Phase 1/1b clinical trial in patients with refractory T cell lymphomas have shown promising tumor responses. Corvus plans to advance soquelitinib into a Phase 3 clinical trial for patients with relapsed peripheral T cell lymphoma (PTCL). Additionally, soquelitinib is being tested in a randomized placebo-controlled Phase 1 trial for atopic dermatitis.

Research into soquelitinib’s mechanism of action suggests it can skew immune responses towards Th1 cells while inhibiting Th2 and Th17 cells. This has significant implications for enhancing immune responses to tumors and controlling T cell exhaustion, a common challenge in current immunotherapy and CAR-T therapies. By influencing T cell differentiation, soquelitinib has the potential to generate more cytotoxic T cells and cytokines that inhibit cancer cell survival, while also preventing the development of autoimmune and allergic diseases.

Corvus Pharmaceuticals believes that targeting specific molecular pathways in T cells can offer therapeutic benefits for patients with various cancers, including solid tumors, and those suffering from autoimmune and allergic conditions. The promising data from recent research supports the continued development and clinical evaluation of soquelitinib and other ITK inhibitors.

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