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Research Findings on ITK Inhibitor Soquelitinib Published in Nature Partner Journal
Angel Pharmaceuticals, together with Corvus Pharmaceuticals, Peking University Cancer Hospital, and multiple other institutions, has conducted in-depth research on soquelitinib, a selective ITK inhibitor that modulates tumor immunity. The research demonstrates that soquelitinib, through selective inhibition of ITK, influences T-cell differentiation, induces Th1 skewing, and enhances antitumor immunity, providing a new potential strategy for cancer immunotherapy. The related research findings were recently published in npj Drug Discovery, a member of the Nature Portfolio's partner journals (nature partner journals) series.
ITK is a kinase that plays a key role in T-cell activation, proliferation, and differentiation. In mouse models, selective knockout of the ITK gene leads to a Th1-skewed T-helper cell differentiation profile. Soquelitinib, as a covalent ITK inhibitor, exhibits more than 100-fold higher selectivity for ITK inhibition compared to the related kinase RLK. The research team conducted in-depth studies on the chemical properties and biological effects of soquelitinib, finding that it preferentially inhibits Th2 cytokine production in vitro while relatively preserving Th1 cytokine secretion; in vivo, it inhibits the growth of multiple syngeneic mouse tumors, including tumors that do not express ITK. Furthermore, soquelitinib treatment increases the infiltration of normal CD8+ T cells with enhanced effector function into tumors, reduces the expression of T-cell exhaustion markers, and restores the effector function of exhausted T cells.
Soquelitinib not only performed excellently in in vitro experiments but also achieved remarkable results in in vivo studies. In mouse tumor models, soquelitinib as monotherapy significantly inhibited the growth of multiple tumors, including CT26 colon adenocarcinoma, RENCA renal carcinoma, B16F10OVA melanoma, A20 B-cell lymphoma, and EL4, without showing direct cytotoxicity. Further studies revealed that soquelitinib treatment increases intratumoral CD8+ T-cell infiltration and enhances their cytotoxic capacity, as evidenced by increased production of inflammatory cytokines and enhanced CD107a degranulation. In addition, when combined with anti-PD-1 and anti-CTLA-4 antibodies, soquelitinib demonstrated synergistic effects, further enhancing antitumor efficacy and inducing long-term antitumor immune responses. Mechanistic studies found that soquelitinib treatment induces a Th1-skewed tumor microenvironment, characterized by upregulation of CXCR3 expression, increased numbers of Tbet-positive CD4 cells, while reducing the expression of T-cell exhaustion markers and restoring the function of exhausted T cells.
Angel Pharmaceuticals has played a significant role in the R&D process of soquelitinib. In 2024, the company obtained the clinical trial approval from the National Medical Products Administration (NMPA) for a Phase II clinical trial of the ITK inhibitor CPI-818 in relapsed/refractory peripheral T-cell lymphoma (RR-PTCL) in China, and is preparing for an IND application for atopic dermatitis (AD). We are also very pleased to see the broader potential opportunities for this first-in-class ITK inhibitor in the fields of oncology and autoimmune diseases.
If you are interested in these research findings, you can further view them at: https://www.nature.com/articles/s44386-024-00002-1
About Angel Pharmaceuticals
Angel Pharmaceuticals is an innovative drug company dedicated to oncology and autoimmune diseases. With the mission of benefiting Chinese patients, Angel is committed to bringing globally top-tier innovative drugs for serious diseases such as cancer and autoimmune disorders to China. In October 2020, Angel Pharmaceuticals completed its Series A financing round, co-invested by Beta Fund, Hisun Pharmaceuticals, Tigermed, and Puhua Investment, and established a strategic partnership with Corvus Pharmaceuticals (CRVS) of the U.S. For more information, please visit www.angelpharma.com.
