Publication of Preclinical Data in Science Signaling Demonstrated the Potential of ITK Inhibition with Soquelitinib as a Novel Approach to Treatment of Inflammatory Diseases
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Data demonstrated in vitro and in vivo ITK inhibition with soquelitinib induced switching of proinflammatory Th17 cells into anti-inflammatory Treg cells
Publication confirms and extends understanding of ITK inhibition mechanism of action and its potential in inflammatory autoimmune and allergic diseases
Data published by leading researchers from Cornell University in peer-reviewed journal Science Signaling
July 25, 2024 -- Corvus Pharmaceuticals, Inc. (Corvus or the Company) (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, today announced data published by leading researchers from Cornell University (Cornell) in Science Signaling, a peer-reviewed journal, that further corroborates Corvus’ views of the potential of ITK inhibition as a novel approach to treating inflammatory diseases. Researchers at Cornell utilized soquelitinib (formerly CPI-818), the Company’s selective ITK inhibitor, to demonstrate in vitro and in vivo that ITK inhibition induces switching of proinflammatory Th17 cells into anti-inflammatory Treg suppressor cells. The article states “The findings of this study provide greater insight into how ITK controls the Th17 and Treg dichotomy, and these findings could have broader implications for immune disorders with an imbalance of Th17 and Treg.”
“The results published by the Avery Lab at Cornell University expands upon our knowledge of the mechanism of action of ITK inhibition in immunology. The results confirm the broad potential for ITK inhibition to treat a range of indications,” said James Rosenbaum, M.D., senior vice president of research at Corvus. “Importantly, their data demonstrated that the mechanism has a dual-effect, decreasing inflammatory Th17 cells by converting them into anti-inflammatory Treg cells. This conversion is highly relevant for autoimmune, allergic and inflammatory diseases. This was elegantly demonstrated in an in vivo asthma model of allergic airway inflammation in which treatment with soquelitinib reduced inflammation by increasing the ratio of Treg to Th17 cells in the lungs.”
The article titled “The kinase ITK controls a Ca2+-mediated switch that balances Th17 and Treg cell differentiation” was published in the peer-reviewed journal Science Signaling and is available for viewing at DOI: 10.1126/scisignal.adh2381. The senior author is Avery August, Ph.D., Professor of Immunology, Department of Microbiology and Immunology at Cornell University College of Veterinary Medicine. Dr. August’s research group focuses on the tyrosine kinases in the regulation of the immune response and the role of intracellular signaling in regulating T cell differentiation and cytokine production, particularly inflammatory and anti-inflammatory cytokines.
Key results from the third-party preclinical studies described in the article demonstrated that soquelitinib had the following observed effects in vitro and in in vivo models of inflammatory disease:
ITK controls the switch between Th17 and Foxp3+ Treg cells
In in vitro experiments, ITK inhibition with soquelitinib results in dose dependent inhibition of Th17 cell differentiation along with an increase in Foxp3+ Treg cells
Switched Foxp3+ Treg cells suppress naïve T cell proliferation and behave like true Treg cells
Soquelitinib treatment of mice with allergic (house dust mite) airway inflammation significantly reduced the percentage of Th17 cells in the lung resulting in an increase in the ratio of Treg to Th17 cells
Corvus’ ITK inhibitors include soquelitinib, which was used in the preclinical studies described in the article, and several next-generation molecules that are being optimized [in preclinical studies] for use in a variety of inflammatory and immune disease indications. Soquelitinib is currently in clinical trials for oncology and immunology indications.
About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company pioneering the development of ITK inhibition as a new approach to immunotherapy for a broad range of cancer and immune diseases. The Company’s lead product candidate is soquelitinib, an investigational, oral, small molecule drug that selectively inhibits ITK. Its other clinical-stage candidates are being developed for a variety of cancer indications. For more information, visit www.corvuspharma.com.
About Soquelitinib
Soquelitinib (formerly CPI-818) is an investigational small molecule drug given orally designed to selectively inhibit ITK (interleukin-2-inducible T cell kinase), an enzyme that is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function. Based on interim results from a Phase 1/1b clinical trial in patients with refractory T cell lymphomas, which demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, the Company plans to initiate a registrational Phase 3 clinical trial of soquelitinib in patients with relapsed PTCL. Soquelitinib also is now being investigated in a randomized placebo controlled phase 1 clinical trial in patients with atopic dermatitis. The immunologic effects of soquelitinib lead to what is known as Th1 skewing and inhibition of Th2 and Th17 cells. Research on soquelitinib’s mechanism of action suggests that it has the potential to control differentiation of normal T helper cells and enhance immune responses to tumors by augmenting the generation of cytotoxic killer T cells and the production of cytokines that inhibit cancer cell survival. Soquelitinib has also been shown to prevent T cell exhaustion, a major limitation of current immunotherapy and CAR-T therapies. Soquelitinib has 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 their secreted 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 Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with cancers, including solid tumors, and in patients with autoimmune and allergic diseases.
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