On July 6, 2023 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported the publication of preclinical data on soquelitinib (formerly known as CPI-818), the Company’s ITK inhibitor product candidate, which highlighted the selective inhibition of ITK to potentially enhance anti-tumor immune response to hematologic and solid tumors and provide a novel approach to cancer immunotherapy (Press release, Corvus Pharmaceuticals, JUL 6, 2023, View Source [SID1234633075]).
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The publication, entitled "Selective Inhibition of Interleukin 2 Inducible T Cell Kinase (ITK) Enhances Anti-Tumor Immunity in Association with Th1-skewing, Cytotoxic T cell Activation, and Reduced T Cell Exhaustion," provides a detailed overview of the chemical structure, enzymatic activity and immunobiologic properties of soquelitinib. The published research was a result of collaborations between scientists at Corvus and researchers at the University of Michigan, The Ohio State University, Peking University and Stanford University. The publication is now available online as a preprint at bioRxiv.org and on the Publications and Presentations page of the Corvus website.
"This significant scientific report demonstrates the potential of highly selective ITK inhibition, now enabled by soquelitinib. The data indicate that this mechanism, if approved, may become the backbone of a new immunotherapy approach to cancer and we believe it will extend the opportunity for the continued development of soquelitinib as a single agent or in combination with other therapies to treat a variety of cancer tumor types," said Richard A. Miller., co-founder, president and chief executive officer of Corvus.
The findings reported indicate that ITK is a novel drug target and its blockade may enhance the body’s immune response to cancer. ITK is an enzyme predominantly expressed by T lymphocytes. ITK plays a major role in the function of T cells which are generally acknowledged as a critical cell in the immunotherapy of cancer. Soquelitinib is currently being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed T cell lymphoma (TCL). Corvus plans to meet with the FDA in the third quarter of 2023 to discuss a Phase 3 registration clinical trial in patients with relapsed TCL.
Key results from the preclinical studies described in the publication demonstrated that soquelitinib:
Is a covalent, irreversible inhibitor that selectively binds to and inhibits ITK function while sparing other closely related kinases, including resting lymphocyte kinase (RLK).
Inhibited Th2 T cell function and the production of various Th2 cytokines leading to Th1 skewing and production of interferon gamma and tumor necrosis factor, which are important cytokines in tumor rejection. Th2 cytokines have been previously implicated in promoting tumor growth and are also involved in autoimmune and allergic diseases.
Activated cytotoxic killer cells and increases infiltration of these cells into tumors.
Reduced and reversed T cell exhaustion resulting in a more potent and prolonged immune response. T cell exhaustion is often a major reason for resistance to immune checkpoint therapy.
Led to in vivo anti-tumor activity in several mouse tumor models, including colon, renal, melanoma, B cell and T cell tumors.