Results in patients with relapsed refractory NSCLC and head and neck cancer demonstrate tumor reduction in patients treated with mupadolimab mono and combination therapy

Corvus enrolling additional patients with these cancers in a Phase 1b/2 trial, with additional data anticipated in 2022

Corvus to host conference call and webcast today at 9:00 a.m. ET / 6:00 a.m. PT

BURLINGAME, Calif., Nov. 12, 2021 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, today announced updated results from its Phase 1/1b clinical trial of mupadolimab (formerly CPI-006), a humanized monoclonal antibody directed against CD73 with a proposed unique mechanism of activating B cells to generate immune responses to tumor antigens and viruses, and inhibiting the production of immunosuppressive adenosine in the tumor microenvironment. The clinical data, along with pre-clinical data, further strengthen mupadolimab’s mechanism of action and demonstrate its potential anti-tumor activity in cancer patients.

The data were made available today in an on-demand, electronic poster format for registered participants of the Society for Immunotherapy of Cancer (SITC) Annual Meeting, which is taking place from November 10 to 14, 2021. The poster is also being presented in-person at SITC 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.

“We continue to broaden our understanding of mupadolimab’s unique characteristics as an anti-CD73 antibody that exhibits potent blockade of adenosine production as well as powerful adenosine-independent effects on the immune system that result in enhanced B cell and T cell function,” said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “Recent research has demonstrated that B cells have a vital role in the immune response to tumors from non-small cell lung cancer (NSCLC) and head and neck squamous cell cancers (HNSCC) each frequently containing high numbers of B cells in the tumor and tumor microenvironment. In our Phase 1/1b clinical trial, treatment with mupadolimab in these cancers resulted in tumor regression in patients that failed to respond to, and progressed through prior treatment with anti-PD(L)-1 therapy. This suggests that, in some patients, mupadolimab’s novel mechanism of action may overcome resistance to anti-PD(L)1 therapies.”

Dr. Miller added, “In addition, the results presented at SITC provide important data on the immunologic effects of mupadolimab, as well as pharmacokinetic, pharmacodynamic and safety data for monotherapy and combination therapy. Looking forward, we are now enrolling additional patients with HNSCC and NSCLC in expansion cohorts. These patients will receive the combination of mupadolimab and pembrolizumab and we anticipate reporting results from these expansion cohorts in early 2022. We believe that the data presented at SITC and data obtained from ongoing expansion cohorts may provide the rationale for a randomized controlled study of mupadolimab, which we expect could begin in 2022.”

Mupadolimab Phase 1/1b Clinical Trial Key Results Presented at SITC 2021
Mupadolimab is being studied in a Phase 1/1b clinical trial in patients with a variety of advanced, refractory cancers, including NSCLC and HNSCC that have failed previous treatment with anti-PD-1 therapy and chemotherapy. The study design included mupadolimab dose escalation from 1 mg/kg to 24 mg/kg intravenous infusion every 3 weeks until disease progression or dose limiting toxicities were reached. Cohorts of patients were treated with mupadolimab monotherapy; combination with ciforadenant, Corvus’ small molecule inhibitor of the A2A receptor; combination with pembrolizumab; or triplet combination with ciforadenant and pembrolizumab.

The data presented at SITC showed that mupadolimab doses of 12mg/kg are optimal, resulting in complete occupancy of the CD73 target and maximal effects on B cell activation. In the assessment of anti- tumor activity in patients receiving optimal doses of mupadolimab, tumor regression (not meeting the threshold for partial response by RECIST) was seen in five patients who had progressive disease as best response to most recent therapy, which included anti-PD(L)1 therapy (see waterfall plot below). This indicates that tumor regression could occur in patients with tumors refractory to anti-PD(L)1 that are treated with mupadolimab.

A figure accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/ac603eab-a2ad-4bd3-be9c-4d854aefcbf8

“The findings of tumor regression with mupadolimab in patients who had grown through their most recent prior therapy with an anti-PD(L)1 is noteworthy. This supports the possibility that mupadolimab’s mechanism of action could serve to add to effectiveness or overcome limitations of current anti-PD(L)1 therapies. This activity would be expected to be more impactful in patients treated earlier in their disease, with less prior therapies,” said Dr. Luke. “We look forward to expanding our experience with mupadolimab in combination with anti-PD(L)-1 in earlier lines of therapy.”

Additional mupadolimab oncology program highlights from the SITC poster presentation include:

• Pharmacokinetic (PK) and pharmacodynamic (PD) results showed complete CD73 target occupancy with mupadolimab at doses of 12 mg/kg and higher. Doses up to 18 mg/kg were tolerated without dose limiting toxicities.
• Within 30 minutes of mupadolimab intravenous infusion, a reduction in B cells in blood was seen, consistent with redistribution of B cells to lymphoid tissues.
• Corvus presented updated preclinical data characterizing mupadolimab’s dual mechanism of action: Mupadolimab is an IgG1 humanized antibody that has been engineered to be Fc gamma receptor binding deficient. Lab data demonstrated that it completely blocks adenosine production from AMP without a hook effect, which is a reduction in binding with higher concentrations of antibody that may limit efficacy to a narrow range of concentrations. In vitro studies showed that binding of mupadolimab to B cells stimulates activation and differentiation into plasmablasts (antibody producing cells) in a mechanism that is independent of adenosine. In vitro studies showed that T cell functions are inhibited by adenosine monophosphate (AMP) and restored by the addition of mupadolimab.
• Corvus analyzed CD73 expression in tumor biopsies, obtained from outside sources, using immunohistochemistry from 75 patients with NSCLC and 31 patients with HNSCC. High CD73 expression was seen in tumor cells and/or stroma in all patients. In HNSCC, CD73 expression is predominantly stromal.

Corvus is also developing mupadolimab as a therapeutic for infectious disease, starting with COVID-19. Preclinical data with humanized mice (mice with human immune system) inoculated with SARS-CoV-2 and influenza viral antigens showed that treatment with mupadolimab enhanced antibody responses that were viral specific, demonstrating its potential to be a universal therapy or adjuvant for viral diseases. In September, Corvus announced results from its Phase 3 clinical trial of mupadolimab for COVID-19, which have been published online at medRxiv.org. The results, which cover 40 patients that were enrolled in the trial prior to its voluntary discontinuation, suggest improvement in the primary and key secondary endpoints in patients treated with single doses of mupadolimab at 2mg/kg and 1mg/kg compared to placebo. Due to the small sample size, the results did not reach statistical significance. No drug related adverse events were reported in the trial.

Conference Call, Webcast and Presentation Slides
Corvus will host a conference call and webcast today, November 12, 2021, at 9:00 a.m. ET (6:00 a.m. PT), to discuss the update on mupadolimab and other topics. The conference call can be accessed by dialing 1-877-407-0784 (toll-free domestic) or 1-201-689-8560 (international) and using the conference ID 13724618. The live webcast, which will include presentation slides, may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus' website for 90 days.

About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company. Corvus’ lead product candidate is mupadolimab (CPI-006), a humanized monoclonal antibody directed against CD73 that has exhibited immunomodulatory activity and activation of immune cells in preclinical studies. The Company’s second clinical program, CPI-818, is 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. Its third clinical program, ciforadenant (CPI-444), is an oral, small molecule inhibitor of the A2A receptor. For more information, visit www.corvuspharma.com.

About Mupadolimab
Mupadolimab (CPI-006) is an investigational, potent humanized monoclonal antibody that is designed to react with a specific site on CD73. In preclinical studies, it has demonstrated immunomodulatory activity resulting in activation of lymphocytes, induction of antibody production from B cells and effects on lymphocyte trafficking. While there are other anti-CD73 antibodies and small molecules in development for treatment of cancer, such agents react with a different region of CD73. Mupadolimab is designed to react with a region of the molecule that acts to stimulate B cells and block production of immunosuppressive adenosine. Mupadolimab is being studied in combination with pembrolizumab in a Phase 1b/2 clinical trial in patients with advanced head and neck cancers and in patients with NSCLC that have failed chemotherapy and anti-PD(L)1 therapy. It is postulated that the activation of B cells will enhance immunity within the tumors of these patients, leading to improved clinical outcomes.

Forward-Looking Statements
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of mupadolimab, such as mupadolimab’s potential anti-tumor activity in cancer patients and whether its novel mechanism of action may overcome resistance to anti-PD(L)1 therapies; the Company’s ability and Angel Pharmaceutical’s ability to develop and advance product candidates into and successfully complete preclinical studies and clinical trials, including the Company’s Phase 1b/2 clinical trial of mupadolimab , and the timing of the availability and announcement of clinical data and certain other product development milestones such as the timing of announcing data for the expansion cohorts in the Company’s Phase 1b/2 clinical trials for mupadolimab and when a randomized controlled study of mupadolimab could begin.    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, 2021, filed with the Securities and Exchange Commission on November 1, 2021, 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 Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of mupadolimab, CPI-818 and ciforadenant; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete preclinical studies and clinical trials; the results of preclinical studies may not be predictive of future results; the unpredictability of the regulatory process; regulatory developments in the United States and other foreign countries; the costs of clinical trials may exceed expectations; the Company’s ability to accurately estimate the amount of net cash used in operating activities for the remainder of the fiscal year; 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 

Figure

 

HNSCC AND NSCLC AT MUPADOLIMAB DOSES ≥ 12 MG/KG

Source: Corvus Pharmaceuticals, Inc.