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 Vitalant to continue studying potential for ITK inhibition to be developed within antiproliferative and “block-and-lock” HIV cure strategies

BURLINGAME, Calif., Feb. 21, 2023 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (Corvus or the Company) (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, today announced new data demonstrating the potential of CPI-818, the Company’s ITK inhibitor, to reduce the need for chronic human immunodeficiency virus (HIV) therapy. The data were presented today at the 30^th Annual Conference on Retroviruses and Opportunistic Infections (CROI), which is taking place from February 19-22, 2023 in Seattle, WA.

“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 Satish K. Pillai, Ph.D., co-author and Professor, School of Medicine at University of California, San Francisco and Senior Investigator, Viral Pathogenesis, at Vitalant Research Institute. “These data suggest that the inhibition of latency reversal and the related anti-proliferative effect on HIV infected cells could be used in a “block-and-lock” strategy to permanently suppress HIV once viral load has been reduced to undetectable levels – eliminating the need for life-long antiretroviral therapy.”

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 Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “The presentation by Dr. Pillai and his team provides evidence of CPI-818’s potential to improve care for people living with HIV, building on the clinical evidence and research on the effects of ITK inhibition on immune function that has already been demonstrated in lymphoma, autoimmunity, allergy and other infectious diseases. We view ITK as a platform target with the potential to support the development of multiple therapeutic agents possessing different immunomodulatory properties, and such work is now ongoing at Corvus.”

The study presented at the CROI meeting was led by Dr. Pillai and Prerna Dabral, Ph.D. of The University of California San Francisco-Bay Area Center for AIDS Research (UCSF-Bay Area CFAR) and supported by Corvus and Vitalant. Drs. Pillai and Dabral will continue to explore the potential of ITK inhibition to develop novel strategies for HIV cure.

The poster presentation can be found on the Corvus website here.

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. 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 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.

Forward-Looking Statements
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 September 30, 2022, filed with the Securities and Exchange Commission on November 3, 2022, 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 results of preclinical studies and interim data from clinical trials not being predictive of future results; 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 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