Preclinical data supports targeting ITK as a new approach for cancer immunotherapy

Novel mechanism of action modulates T cell differentiation and enhances the immune system via Th1 skewing, increased T cell cytolytic capacity and reduction of T cell exhaustion

Enrollment continues in Phase 1/1b clinical trial of CPI-818 for the treatment of refractory T cell lymphoma, including use of minimum absolute lymphocyte count (ALC) predictive biomarker for patient selection

BURLINGAME, Calif., April 17, 2023 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, today 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 (AACR) Annual Meeting, which is taking place April 14-19, 2023 in Orlando, FL.

“The preclinical and laboratory data presented at AACR demonstrates the potential of targeting ITK with CPI-818 to modulate T cell differentiation and enhance the immune system’s ability to kill both solid and hematological cancers,” said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “CPI-818 inhibited tumor growth in five different tumor models including colon, renal and melanoma cancers, and in both T and B cell lymphomas. This work builds upon the immunologic properties and anti-tumor activity already seen in our ongoing Phase 1/1b clinical trial in T cell lymphoma, and we now believe we can extend this approach to a wide range of solid tumors. Our data presented at AACR shows that CPI-818’s novel mechanism of action involves multiple synergistic features including Th1 skewing, increases in T cell cytolytic capacity and reduction in T cell exhaustion. These properties are a result of the myriad of functions that ITK plays in T cell biology. Together, we believe these characteristics position CPI-818 to potentially lead the next generation of tumor immunotherapy if approved.”

Dr. Miller added, “We are excited by the long-term potential of CPI-818 across a broad range of cancer indications, but in the near-term our main focus is continuing enrollment in our T cell lymphoma (TCL) Phase 1/1b clinical trial and meeting with the FDA to discuss a potential registration randomized Phase 3 clinical trial.”

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 (abstract #1813) today 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 (TNF) 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 naïve 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 (IFNg). 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 (ACL) 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.

About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company. Corvus’ lead product candidate is CPI-818, an investigational, oral, small molecule drug that selectively inhibited ITK in preclinical studies and is in a multicenter Phase 1/1b clinical trial in patients with several types of T cell lymphomas. The Company’s second clinical program, ciforadenant (CPI-444), is an oral, small molecule inhibitor of the A2A receptor that is in an open-label Phase 1b/2 clinical trial in front-line renal cell cancer. Its third clinical program, mupadolimab (CPI-006), is a humanized monoclonal antibody directed against CD73 that has exhibited immunomodulatory activity and activation of immune cells in preclinical and clinical studies. For more information, visit www.corvuspharma.com.

About CPI-818
CPI-818 is an investigational small molecule drug given orally that has selectively inhibited ITK (interleukin-2-inducible T cell kinase) in preclinical studies. It was designed to block malignant T cell growth and to modulate immune responses. ITK, an enzyme, is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell lymphomas and leukemias, as well as in normal immune function. Recent clinical data in T cell lymphomas suggests that CPI-818 has the potential to control differentiation of T helper cells and enhance immune responses to tumors. Interference with ITK signaling also can modulate immune responses to various antigens. Optimal doses of CPI-818 have been shown to affect T cell differentiation and induce the generation of Th1 helper cells while blocking the development of both Th2 and Th17 cells and production of Th2 related cytokines. Th1 T cells are required for immunity to tumors, viral infections and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. The immunologic effects of CPI-818 lead to what is known as Th1 skewing and is made possible by the high selectivity of CPI-818 for ITK. The Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with T cell lymphomas, solid tumors, and in patients with autoimmune and allergic diseases. The Company is conducting a Phase 1/1b trial in patients with refractory T cell lymphomas that was designed to select the optimal dose of CPI-818 and evaluate its safety, PK, target occupancy, immunologic effects, biomarkers and efficacy. Interim data from the Phase 1/1b clinical trial of CPI-818 for T cell lymphoma demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, and identified a dose that maximally affects T helper cell differentiation.

Forward-Looking Statements
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of CPI-818, ciforadenant and mupadolimab, including CPI-818’s potential to treat a wide range of solid tumors and hematologic cancers; the Company’s ability and its partner’s ability, as well as the timing thereof, to develop and advance product candidates into and successfully complete preclinical studies and clinical trials, including the Company’s Phase 1/1b clinical trial of CPI-818 and the Company’s planned meeting with the FDA to discuss a Phase 3 registration clinical trial with CPI-818 for T cell lymphoma later this year; and the timing of the availability and announcement of clinical data and certain other product development milestones, including presenting updated data from the Phase 1/1b clinical trial of CPI-818 in the second quarter of 2023. All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022, filed with the Securities and Exchange Commission on March 28, 2023, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of CPI-818, ciforadenant and mupadolimab; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete preclinical studies and clinical trials; the results of preclinical studies and interim data from clinical trials not being predictive of future results; the unpredictability of the regulatory process; regulatory developments in the United States, and other foreign countries; the costs of clinical trials may exceed expectations; and the Company’s ability to raise additional capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

INVESTOR CONTACT:
Leiv Lea
Chief Financial Officer
Corvus Pharmaceuticals, Inc.
+1-650-900-4522
llea@corvuspharma.com

MEDIA CONTACT:
Sheryl Seapy
Real Chemistry
+1-949-903-4750
sseapy@realchemistry.com