SITC presentation builds on data at ASCO in June, adding evidence supporting a new immuno-oncology approach with CPI-006 via activation of immune cells and the inhibition of adenosine productionCompany also presents data supporting potential of Adenosine Gene Signature to serve as a biomarker to identify patients that are likely to respond to CPI-006 and ciforadenantCompany to host investor and analyst reception today at 6:00 pm ETBURLINGAME, Calif., Nov. 08, 2019 (GLOBE NEWSWIRE) — Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies with biomarker patient enrichment selection, today announced updated results from its Phase 1/1b trial of CPI-006, the Company’s anti-CD73 antibody. The clinical data continue to support a novel mechanism of action involving the activation of immune cells potentially directed against tumors, along with the inhibition of adenosine production. The results will be presented today in an oral session at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in National Harbor, Maryland by Jason J. Luke, M.D., principal investigator of the trial and Director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center and Associate Professor of Medicine at the University of Pittsburgh School of Medicine.“As previously reported at ASCO, our clinical studies continue to demonstrate the novel immunobiological properties of CPI-006,” said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “Based on its ability to activate various immune cells and inhibit the production of adenosine, we believe CPI-006 has potential as a monotherapy and combination medicine for a variety of tumor types. We plan to continue to enroll cancer patients in the CPI-006 Phase 1/1b study at the selected dose of 18 mg/kg, which has been well-tolerated to date and has demonstrated complete occupancy of the target within tumors. In addition, we continue to develop the Adenosine Gene Signature, with additional data from a larger number of patients with renal cell cancer indicating that it could be used as a biomarker driven patient enrichment strategy in future clinical trials which would potentially enable us to select patients most likely to benefit from treatment.”The CPI-006 Phase 1/1b study is currently enrolling patients with a variety of cancers who have failed standard therapies. It is designed to select the dose and evaluate the safety, pharmacokinetics, immune biomarkers and efficacy of CPI-006 as a single agent; in combination with ciforadenant (CPI-444), a selective and potent inhibitor of the adenosine A2A receptor; and in combination with pembrolizumab, an anti-PD-1 antibody. Once the optimum dose is identified, pre-specified disease specific expansion cohorts will enroll patients with metastatic castration resistant prostate cancer (mCRPC), renal cell cancer (RCC), non small cell lung cancer (NSCLC) and other cancers. The efficacy endpoints are complete response (CR), partial response (PR), disease control rate, duration of response, progression-free survival and overall survival. Based on the data to-date from the dose-escalation portion of the study, the Company has selected a CPI-006 dose of 18 mg/kg every three weeks for continued expansion in the monotherapy arm of the Phase 1/1b study.CPI-006 Phase 1/1b Results at SITC 2019
Today, Dr. Luke will present updated results from the first two arms of the study, which are evaluating CPI-006 as a single agent and in combination with ciforadenant. The presentation includes data from 24 patients who received CPI-006 given intravenously as monotherapy (at doses of 1, 3, 6, 12, 18 or 24 mg/kg every 21 days) and 16 patients who received the combination treatment of CPI-006 (1, 3, 6, 12 or 18 mg/kg every 21 days) plus a fixed dose of ciforadenant (100 mg twice daily). These patients had advanced, refractory disease (12 had colorectal cancer, six had renal cell cancer, six had pancreatic cancer, six had prostate cancer, five had head and neck cancer, three had non-small cell lung cancer, one had bladder cancer and one had sarcoma), and had failed a median of four prior therapies. The key highlights from the CPI-006 clinical results include:Pharmacokinetic studies showed a dose-dependent increase in CPI-006 plasma exposure, with doses of 6 mg/kg and higher producing sustained plasma levels of CPI-006 and doses of 12 mg/kg and higher achieving complete and sustained occupancy of CD73 on peripheral blood lymphocytes.Biopsies revealed penetration of CPI-006 and complete occupancy of CD73 in tumors at doses of 18 mg/kg, which is the selected dose for continued expansion of the study.
In vitro results revealed that CPI-006 induced B-cell differentiation into both plasmablasts and memory B-cells, promoted secretion of immunoglobulin M (IgM), and class switching of the IgM to produce immunoglobulin G (IgG). In vivo results demonstrated that treatment with CPI-006 produced changes in blood B-cell and T-cell levels, highlighted by a reduction in circulating B-cells within 30 minutes of treatment, with a partial return by 21 days, and with returning B-cell levels heavily enriched with memory B-cells. These changes are consistent with the in vitro findings that suggest that CPI-006 induces a humoral adaptive immune response.A specific analysis of the B-cell receptor repertoire (the range of B-cell receptors expressed by the total B-cell population) revealed that several patients exhibited the induction of new memory B-cell clones in blood following treatment with CPI-006, with clonal frequencies as high as 1%, supporting a very strong antibody immune response comparable or exceeding that seen when patients receive vaccinations. These findings are consistent with antigen driven clonal expansion of B-cells.In evaluable patients receiving 6 mg/kg and higher in the protocol defined, pre-specified disease specific cohorts, tumor regression was seen in four of nine patients: mCRPC (one of two patients; reduction of 18.2%), RCC (two of five patients; reduction of 7.0%, 21.3%) and NSCLC (one of two patients; reduction of 5.8%).A patient with metastatic prostate cancer that had previously failed multiple anti-androgen therapies and chemotherapy received over 19 cycles (a cycle equals 21 days) of CPI-006 monotherapy at a dose of 6 mg/kg and showed reduction in tumor volume and a reduction in bone pain.CPI-006 was well tolerated at all dose levels, with no dose-limiting toxicities. Grade 1 infusion reactions were detected (N=3 patients) and mitigated with premedication with acetaminophen and antihistamine. Grade 3 or 4 toxicities included a grade 3 anemia (N=1) and a grade 3/4 diarrhea (N=1).“CPI-006 is an anti-CD73 antibody that has powerful immunomodulatory effects,” said Dr. Luke. “Its in vivo effects are rapid and include the redistribution of B-cells and T-cells, with returning B-cells demonstrating a phenotype that indicates sensitization with antigen. Our B-cell receptor studies demonstrated selective clonal expansion to antigens suggesting that CPI-006 may be eliciting an anti-cancer immune response. To-date, this has been supported in patients, some of whom have observed tumor regression when treated with monotherapy or in combination with ciforadenant.”Adenosine Gene Signature Data at SITC 2019
Updated data on the Adenosine Gene Signature will be presented today in a poster session at the SITC Annual Meeting by Stephen Willingham, PhD, Corvus Senior Scientist. The key highlights from the poster include:The Adenosine Gene Signature was examined in 32 patients with advanced refractory renal cell cancer, including 21 that were positive for this biomarker and 11 that were negative for this biomarker. In patients with a positive biomarker result, 17% had a partial response (PR) and many had tumor regression that did not meet the response evaluation criteria in solid tumors (RECIST) for PR. In patients with a negative biomarker result, there were no responses. In the 21 patients in the Adenosine Gene Signature positive group, 9 patients had tumor regression; 4 patients had no change in tumor size; and 8 patients had tumor progression as best response; no patients in the negative group showed tumor reduction. There was a statistically significant correlation of the Adenosine Gene Signature with tumor response, p=0.008.A positive Adenosine Gene Signature was also associated with duration of response. Six of 21 patients had progression free survival (PFS) exceeding 40 weeks, with a plateau on the curve, and all of these patients were Adenosine Gene Signature positive, including four patients who had failed prior therapies with anti PD(L)-1. CPI-006 blocks CD73 enzymatic activity and prevents conversion of adenosine monophosphate (AMP) to adenosine leading to an elevation of AMP levels. AMP induces gene expression changes nearly identical to the Adenosine Gene Signature due to its ability to bind to and activate the adenosine A2A receptor, producing similar effects to that of adenosine binding to the A2A receptor.CD73 antagonists preserve AMP and thereby amplify the AMP gene expression signature.Ciforadenant (which has been shown to inhibit adenosine binding to A2A receptor) blocks both AMP and adenosine induced gene expression changes.This suggests that use of CPI-006 (which has been shown to inhibit adenosine production) in combination with ciforadenant could be a more effective way to block the immunosuppressive effects of A2A receptor signaling.“We continue to confirm the predictive value of the Adenosine Gene Signature in patients with renal cell cancer,” said Dr. Willingham. “Patients with this biomarker have been more likely to respond to adenosine blockade with ciforadenant and we intend to use this biomarker driven enrichment strategy in our future studies with ciforadenant and CPI-006.”SITC Investor and Analyst Reception
Corvus will host an investor and analyst reception today, November 8, 2019, at 6:00 pm ET, to discuss both the CPI-006 data and the Adenosine Gene Signature data presented at SITC 2019. The reception will feature Dr. Luke, Dr. Miller, and members of the scientific and clinical staff at Corvus. The company will offer a live webcast of the reception, which can be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for one year.About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies. Corvus’ lead product candidates are ciforadenant (CPI-444), a small molecule inhibitor of the A2A receptor, and CPI-006, a humanized monoclonal antibody directed against CD73 that exhibits immunomodulatory activity and blockade of adenosine production. These product candidates are being studied in ongoing Phase 1 and 2 clinical trials in patients with a wide range of advanced solid tumors. Ciforadenant is being evaluated in a successive expansion cohort trial examining its activity both as a single agent and in combination with an anti-PD-L1 antibody. CPI-006 is being evaluated in a multicenter Phase 1/1b clinical trial as a single agent, in combination with ciforadenant, and in combination with pembrolizumab. The Company’s third clinical program, CPI-818, an oral, small molecule drug that has been shown to selectively inhibit ITK, is in a multicenter Phase 1/1b clinical trial in patients with several types of T-cell lymphomas. For more information, visit www.corvuspharma.com.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. This antibody also possesses immunomodulatory activity resulting in activation of lymphocytes and effects on lymphocyte trafficking, which are independent of adenosine. In vitro studies of CPI-006 have shown it is capable of substantially inhibiting the production of adenosine by blocking the CD73 enzyme.About Ciforadenant
Ciforadenant (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.Forward-Looking Statements
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of CPI-006 and ciforadenant, the Company’s ability 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 ciforadenant, and the Company’s Phase 1/1b clinical trial of CPI-006, the utility of biomarker data collected and the suitability of dosing regimen selected for clinical trials and the potential utility of the Adenosine Gene Signature to identify patients that are most likely to respond to therapies targeting the adenosine pathway. 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, 2019, filed with the Securities and Exchange Commission on October 29, 2019, 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 accuracy of the Company’s estimates relating to its ability to initiate and/or complete clinical trials; the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of ciforadenant and CPI-006; the Company’s ability to utilize biomarker data and select suitable dosing regimens; the Adenosine Gene Signature may not prove to be useful; the results of preclinical studies may not be predictive of future results; the unpredictability of the regulatory process; and regulatory developments in the United States and foreign countries. 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.comMEDIA CONTACT:
Sheryl Seapy
W2O pure
+1 213-262-9390
sseapy@purecommunications.com
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