Media
[2023 ASH] Angel Pharmaceuticals Successfully Presents Latest Data from Phase I/Ib Clinical Trial of Soquelitinib (ITK Inhibitor)
The 65th American Society of Hematology (ASH) Annual Meeting was successfully held from December 9 to 12, 2023, in San Diego, California, USA. The ASH Annual Meeting is recognized as the largest and most influential annual academic event in the field of hematology worldwide. At this year's meeting, Angel Pharmaceuticals successfully presented the latest data from the Phase I/Ib clinical trial of Soquelitinib (ITK inhibitor) as a poster (#1442). These data revealed important immunomodulatory mechanisms of Soquelitinib, providing critical evidence supporting the clinical application of this ITK inhibitor in lymphomas and solid tumors.
The team led by Professor Zhu Jun from the Department of Lymphoma at Peking University Cancer Hospital, the principal investigator, together with the Angel Pharmaceuticals team at the ASH Annual Meeting site
Dr. Guo Yong, Senior Vice President of Clinical Development at Angel Pharmaceuticals (left)
Professor Richard Miller, Founder and Chairman of Angel Pharmaceuticals (third from right), Dr. Guo Yong, Senior Vice President of Clinical Development at Angel Pharmaceuticals (second from right)
[Key Content of the ASH 2023 Poster Data]
Interleukin-2-inducible T-cell kinase (ITK) plays an important role in the T-cell receptor (TCR) signaling pathway. Soquelitinib (formerly CPI-818), a highly selective covalent-binding ITK inhibitor, is being evaluated in a Phase I/Ib clinical trial (NCT03952078) as monotherapy for the treatment of refractory T-cell lymphomas (TCL). Single-cell RNA sequencing and flow cytometry were performed on patient samples to explore potential prognostic biomarkers and immunomodulatory mechanisms. Through single-cell RNA sequencing analysis of mRNA expression, soquelitinib was found to induce the expression of cytotoxic genes and reduce the expression of exhaustion genes in normal CD8+ cells. Human T-cell differentiation studies and EL4 syngeneic tumor model studies confirmed the immunomodulatory effects of soquelitinib in vitro and in the tumor microenvironment in vivo. Similar results were also observed in mouse syngeneic models of B-cell lymphoma A20, breast cancer 4T1, and colon cancer CT26.WT.
The research data presented at this conference revealed a novel immunomodulatory mechanism, namely that in the tumor microenvironment of patients who responded to soquelitinib treatment, the inhibitor induced normal CD4+ Th1 cells and CD8+ TEMRA cells, while reducing CD4+ Treg cells. These findings demonstrate the potential of soquelitinib as a novel immunotherapy for the treatment of T-cell lymphomas and solid tumors.
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.
About Soquelitinib
Soquelitinib (CPI-818) is an investigational oral small-molecule drug that selectively inhibits ITK (interleukin-2-inducible T-cell kinase) in clinical studies. ITK is an enzyme expressed primarily on T cells and plays a role in T-cell and natural killer (NK) cell lymphomas and leukemias, as well as in normal immune function. The immune effects mediated by soquelitinib result in Th1 skewing, and this effect is attributable to the high selectivity of soquelitinib for ITK. Studies on the mechanism of action of soquelitinib have shown its potential to control the differentiation of normal T helper cells and enhance immune responses by increasing the production of cytotoxic killer T cells and inhibiting the production of cytokines that support cancer cell survival. Soquelitinib has also been shown to prevent T-cell exhaustion, a major limitation of current immunotherapies and CAR-T therapies. It has been demonstrated that the optimal dose of soquelitinib can influence T-cell differentiation, induce the production of Th1 helper cells, while blocking the development of Th2 and Th17 cells and the production of Th2-related cytokines. Th1 T cells are essential for tumor immunity, viral infections, and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. Angel Pharmaceuticals believes that inhibiting this specific molecular target in T cells may have therapeutic benefits for patients with cancers, including solid tumors, as well as those with autoimmune and allergic diseases. This is based on interim results from a Phase I/Ib clinical trial in patients with refractory T-cell lymphomas, which has demonstrated efficacy in a very advanced, relapsed/refractory T-cell malignancy population.
