On October 22, 2018 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies, reported new data on a biomarker associated with patient response to therapy with CPI-444, an adenosine receptor antagonist. This "adenosine gene signature" has the potential to be used as a predictive biomarker for patient selection in future clinical studies of CPI-444 and other therapies targeting the adenosine pathway, including CPI-006 (Press release, Corvus Pharmaceuticals, OCT 22, 2018, View Source [SID1234530341]). The biomarker data was presented today in a poster discussion session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in Munich, Germany, by Stephen Willingham Ph.D., a senior scientist at Corvus.
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CPI-444, Corvus’ lead product candidate, is a selective and potent inhibitor of the adenosine A2A receptor. It is currently being evaluated in clinical trials in patients with various solid tumors as a single agent and in combination with Genentech’s atezolizumab, an anti-PD-L1 antibody. CPI-006 is a humanized monoclonal antibody directed against CD73. It is currently being evaluated in an early-stage, three-arm clinical trial in patients with a variety of solid tumors as a single agent, in combination with CPI-444, and in combination with pembrolizumab, an anti-PD-1 antibody.
"The gene expression profiles associated with the adenosine pathway have been shown to lead to the secretion of various inflammatory cytokines and chemokines that recruit suppressive myeloid cells and dampen T-cell function. The biomarker data presented at ESMO (Free ESMO Whitepaper) demonstrates that in vitro and in vivo treatment of human immune cells with CPI-444 blocks the expression of this adenosine gene signature, confirming its mechanism of action," said Dr. Willingham. "The expression of the adenosine gene signature has been shown to correlate with tumor regression in our ongoing Phase 1/1b trial of CPI-444 for the treatment of patients with renal cell carcinoma (RCC). In the trial, patients with high expression of the adenosine gene signature were more likely to have tumor regression than those patients with low expression (p<0.008). Our data, together with other recently published data, indicate that tumors with an adenosine-rich environment are resistant to therapy with anti-PD-(L)1 antibodies, and provide support for the addition of CPI-444 to these therapies to enhance efficacy."
"Our discovery of the adenosine gene signature biomarker represents a major step forward for therapies based on blockade of the adenosine pathway," said Richard A, Miller M.D., an oncologist; co-founder, president and chief executive officer of Corvus. "This biomarker could potentially be used in the future to select patients most likely to benefit from adenosine blockade with either CPI-444 or antibodies that inhibit adenosine production, such as CPI-006. These data, as well as our ongoing trials with CPI-444 and CPI-006, continue to advance the field and confirm the mechanism of action of CPI-444 and adenosine antagonism. Additional data on these programs will be presented at the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in November."
About CPI-444
CPI-444 is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine. In vitro and preclinical studies have shown that dual blockade of CD73 and the A2A receptor may be synergistic.
About CPI-006
CPI-006 is a potent humanized monoclonal antibody that reacts with the active site of CD73, blocking the conversion of AMP to adenosine. In vitro studies of CPI-006 have shown it is capable of substantially inhibiting the production of adenosine by blocking the CD73 enzyme.