Corvus Pharmaceuticals Announces New Data Demonstrating CPI-818’s (ITK Inhibitor) Potential to Block HIV Latency Reversal
Findings may provide a treatment that enables discontinuation of HIV antiretroviral therapy by preventing re-emergence of the virus
Data to be presented at the Conference on Retroviruses and Opportunistic Infections
Research partners from UCSF and
“The data presented at the CROI meeting support our ongoing research on the role of ITK in the HIV life cycle and the potential for ITK inhibition with CPI-818 to provide an important new approach to the long-term management of HIV disease,” said
For people living with HIV (PLWH) on antiretroviral therapy, HIV can be reduced to levels below detection limits, which enables the restoration and preservation of immune system function, reduces HIV-associated morbidity and prevents HIV transmission. However, in these individuals the virus persists in a latent form in CD4 cells, which are white blood cells that are a key component of the immune system that are destroyed by HIV. Viral latency is reversed if therapy is discontinued, leading to a re-emergence of replicating HIV and the destruction of CD4 cells, necessitating PLWH to be on life-long therapy.
Previous studies have shown that ITK is involved in several steps in the HIV life cycle and in this study, researchers explored the potential of ITK inhibition with CPI-818 to inhibit the latency reversal of HIV. The study was conducted in two models: (1) a T cell lymphoma cell line latently infected with fluorescence-tagged HIV (in vitro) and (2) CD4+ T cells from the blood of four PLWH (ex-vivo). In both models, the cells were stimulated to reverse viral latency and promote viral replication. The cells were simultaneously treated with various concentrations of CPI-818, and in each of the two models, there was a statistically significant and dose-dependent reduction in the reversal of viral latency (P<0.0001) including four of the four PLWH. In CD4 T cells, CPI-818 inhibited the proliferation of HIV-infected cells more than uninfected cells.
“Our research has shown that ITK plays a critical role in a variety of cellular activities that are important in T cell function and potentially useful for the treatment of a diverse range of diseases, highlighting the broad therapeutic opportunity for ITK inhibition with CPI-818,” said
The study presented at the CROI meeting was led by
The poster presentation can be found on the Corvus website here.
About Corvus Pharmaceuticals
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 and leukemias 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.
About HIV and Latency Reversal
Human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). This RNA virus infects and replicates primarily in CD4+ T cells and ultimately results in severe immunosuppression. There are several antiretroviral agents that control HIV infection and reduce viral load to undetectable levels in the blood. However, the viral genome can integrate into the host DNA and persist there in a latent, non-replicating form. For unknown reasons, when antiretroviral therapy is discontinued and the virus is no longer suppressed, viral latency is reversed and replication with re-emergence of the virus occurs. One approach to solving this problem that is now being explored by researchers is the so-called “block-and-lock” concept, which aims to block latency reversal by locking the virus in its latent form.
This press release contains forward-looking statements, including statements related to the potential of CPI-818 to reduce the need for chronic HIV therapy and to improve care for PLWH; and ITK’s ability to be a platform target with the potential to support the development of multiple therapeutic agents. 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 Quarterly Report on Form 10-Q for the quarter ended
Chief Financial Officer
Source: Corvus Pharmaceuticals, Inc.