Corvus Pharmaceuticals presents new data for CPI-818

Corvus Pharmaceuticals announced new data for CPI-818, the Company’s ITK inhibitor, demonstrating its potential to treat a variety of solid and hematological cancers based on a novel immunotherapy mechanism of action. The data will be presented today in a poster at the American Association for Cancer Research Annual Meeting, which is taking place April 14-19, 2023 in Orlando, FL. CPI-818 Preclinical Data Presented at AACR: The CPI-818 preclinical data was presented by Lih-Yun Hsu, Ph.D., Director of Immunology, Corvus Pharmaceuticals, in a poster session at the AACR Annual Meeting. The key highlights from the poster, which is also available on the Publications and Presentations page of the Corvus website, include: CPI-818 monotherapy (7 days oral administration) provided statistically significant inhibition of growth in established tumors in the following cancer models: CT26 colon cancer, RENCA kidney cancer, B16 melanoma, EL4 TCL and A20 B cell lymphoma. Mechanism studies revealed that CD8 T cells were primarily involved in inhibiting growth in the CT26 colon cancer model and that CD8, CD4 T cells and NK cells were primarily involved in inhibiting growth in the EL4 TCL model. Studies also showed that CPI-818 increased the cytolytic capacity of tumor infiltrating lymphocytes. These cells produce interferon gamma, tumor necrosis factor and perforin, which are cytokines and effector molecules produced by killer T cells. The preclinical data demonstrated that CPI-818 enhances the anti-tumor efficacy of anti-PD1 and anti-CTLA4 therapy in animal models, including at suboptimal doses of these therapies. The triplet combination led to complete tumor elimination in 19 of 20 animals with established CT26 colon cancer tumors. The preclinical data also demonstrated that CPI-818 reduced the expression of T cell exhaustion markers in animals treated with anti-PD1 and anti-CTLA4 therapy. T cell exhaustion is a phenomenon seen in tumors and chronic infections where prolonged exposure to antigens results in exhausted or ineffective T cell function and inability to eliminate tumors or infections. The down-regulation of these T cell exhaustion markers suggests that the inhibition of ITK by CPI-818 potentially produces favorable changes in the tumor microenvironment that could enhance anti-tumor immune system activity. In vitro studies with normal human naive CD4+ T cells demonstrated that CPI-818 suppressed T cell differentiation into Th2 cells and their production of Th2 derived cytokines IL4, IL5, IL9, IL10 and IL17, however it did not affect differentiation into Th1 cells or their production of the cytokine interferon gamma. These findings were the result of Th1 skewing. CPI-818 is currently being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed TCL. The Company recently incorporated a minimum absolute lymphocyte count as an eligibility criterion for enrollment in the clinical trial and anticipates presenting updated data from this trial at a medical meeting in the second quarter 2023. Based on the current enrollment rate of this clinical trial, the Company believes that the number of patients treated in this clinical trial would provide adequate safety and preliminary efficacy data to inform the design of a potential registration Phase 3 randomized clinical trial. As recommended by the FDA, the Company plans to meet with the FDA to discuss such a clinical trial; it is anticipated that this meeting will take place later this year.