Characterization of novel immunotherapy approach with CPI-006 and details of COVID-19 clinical trial results submitted for publication online at medRxiv.org

Patients treated in first two cohorts of Phase 1 study had low pre-treatment titers of antibodies and produced robust antibody responses within 7 days of treatment

Titers of IgG, IgM and neutralizing antibodies continually increased out to 28 days post-treatment

BURLINGAME, Calif., Sept. 10, 2020 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, today announced updated data from its ongoing Phase 1 study investigating the potential for CPI-006 to provide a novel immunotherapy approach for patients with COVID-19. The results demonstrated that all evaluable patients treated in the first two cohorts (0.3 and 1.0 mg dose of CPI-006) of the study produced significant titers of antibody to SARS-CoV-2 within seven days of receiving the treatment, with levels of antibody, including neutralizing antibodies, continually increasing out to 28 days. In addition, all of these patients were discharged from the hospital with clinical improvement and none experienced any drug-related safety issues. The study has completed enrollment in the third cohort (3.0 mg dose of CPI-006) of five patients, with the overall study expected to enroll up to 30 patients.

“The initial data from the first two cohorts of COVID-19 patients treated with the lowest doses of CPI-006 are very encouraging, with patients promptly achieving high titers of anti-SARS-CoV-2 antibodies despite low pre-treatment levels,” said Richard A. Miller, M.D., president and chief executive officer of Corvus. “We believe the robust antibody responses were induced by the B cell activation triggered with CPI-006 in our study and that such responses may effectively eradicate the SARS-CoV-2 virus within treated patients and provide them with prolonged immunity. These results are consistent with the known activity of CPI-006 shown in vitro and in vivo in our ongoing cancer studies where CPI-006 binding to B cells leads to their activation and differentiation into both antibody-producing plasma cells and memory B cells. We have completed enrollment in the third cohort and we plan to meet with FDA to discuss our plans for a pivotal study.”

Dr. Miller added, “CPI-006’s unique immunotherapy approach to treating COVID-19 may provide advantages over other therapies in development. Specifically compared to passively administered monoclonal antibody approaches, we believe CPI-006 could trigger B cell activation at much lower antibody dose levels and provide activity against potential new mutant variants because it works by activating the immune system to generate polyclonal anti-SARS-CoV-2 antibodies. Based on this unique mechanism, we are considering the potential for CPI-006 to be used earlier, including symptomatic outpatients and in combination with vaccination, with the hope that it could limit or eliminate the need for booster injections and produce long-term immunity.”

CPI-006 COVID-19 Phase 1 Study Update
The open-label, Phase 1 study is expected to enroll up to 30 hospitalized COVID-19 patients with mild to moderate symptoms. Patients will receive a single dose of CPI-006, with levels of 0.3, 1.0, 3.0 and 5.0 mg/kg, escalating in four cohorts as the study progresses. Patients will receive medications, therapies, and interventions per standard treatment protocols for COVID-19 for the duration of the study. The primary efficacy endpoint is the change in serum immunoglobulin (IgM and IgG) anti-SARS-CoV-2 levels compared to baseline at day 28. The study also will examine safety and other clinical endpoints, including time to resolution of symptoms and duration of hospitalization.

The Company  has submitted a manuscript describing the initial results from the first two cohorts (five patients receiving 0.3 mg dose and five patients receiving 1.0 mg dose) of the study for publication online at medRxiv.org. In the study, the median age of the patients was 64 years (range 28-76 years) and all the patients had comorbidities that increased their COVID-19 risk: diabetes (4), hypertension (2), obesity (7), and/or cancer (2). The median duration of symptoms prior to treatment with CPI-006 was 8 days (range 1-21 days). The key highlights from these 10 patients, include:

• Nine of 9 patients with pre-treatment serum samples available had low pre-treatment levels of anti-SARS-CoV-2 antibodies independent of the duration of their prior COVID-19 symptoms.
• IgG and IgM antibody titers against the SARS-CoV-2 trimeric spike and/or receptor binding domain (RBD) increased in 8 of 8 evaluable patients within 7 days of a single infusion of low doses of CPI-006.  One patient did not have a pre-treatment serum sample available but had a sample collected one day after receiving CPI-006 and this sample exhibited a high titer, which continued to increase. In five patients measured, the antibodies were neutralizing; one patient with lymphopenia showed a delay in generating neutralizing antibodies.
• In all patients evaluated, the antibody responses continued to increase out to 28 days post treatment with CPI-006. Rising titers of >1:200,000 to spike protein and >1:100,000 to RBD were observed. IgM titers also continued to rise reaching levels of 1:100,000 in some patients. One patient continued to have rising titers beyond 56 days with serum titers of IgG both to spike and to RBD of >102,000. Neutralizing antibody titers also increased progressively out to 28 days, which was the latest time point available.
• In one patient tested, memory B cells increased from 1.8% to 4.8% of B cells at 28 days post treatment with CPI-006, with serum IgG titers to spike and to RBD of >1:50,000.
• In three of three patients tested to-date, CD4 and CD8 T effector memory cells increased by day 28 post treatment with CPI-006 and these cells were shown to respond specifically to SARS-CoV-2 viral antigens.
• All 10 patients were discharged from the hospital with clinical improvement after a median of 4 days.
• There were no drug-related toxicity or safety issues reported.

Additional data from this study is expected to be available in late 2020, including results from the 3.0 and 5.0 mg cohorts and longer follow-up data from the 0.3 and 1.0 mg cohorts. The Company has submitted for a potential presentation of data from this study at the Society for Immunotherapy of Cancer (SITC) annual meeting in November. In addition, if the study meets its objectives, Corvus intends to work with the FDA to initiate a broader, randomized study that could potentially be adapted into a pivotal study to support a regulatory submission for FDA approval.

Background Information on CPI-006 for the Treatment of COVID-19
Corvus is studying an agonistic (immunostimulatory) humanized monoclonal antibody, designated as CPI-006, which has demonstrated a potential new approach to immunotherapy of infectious diseases and cancer. In both in vitro and in vivo studies in cancer patients, CPI-006 has demonstrated binding to various immune cells and the inducement of a humoral adaptive immune response – B cell activation and lymphocyte trafficking leading to the production of antigen-specific immunoglobulin (IgM and IgG) antibodies. Administration of CPI-006 has also led to increased levels of memory B cells, which are the cells responsible for long-term immunity. The similar production of antibodies and memory cells to pathogens such as SARS-CoV-2 may provide immediate and long-term clinical benefits for patients including shortened recovery time and improved long-term protective immunity.

To date, over 90 cancer patients have been treated with CPI-006 in the Corvus Phase 1/1b study, with dosing as high as 24 mg/kg every three weeks. CPI-006 has been well tolerated in these patients and evidence of B-cell activation and lymphocyte trafficking was observed in patients that received single doses as low as 1 mg/kg. Corvus’ study showed that CPI-006 is associated with increases in memory B cells, the emergence of new B cell clones and, in some patients, the production of novel anti-tumor antibodies. These results have been previously reported in presentations at the Society of Immunotherapy of Cancer annual meeting in 2018 and 2019 and in a presentation at the American Society of Clinical Oncology annual meeting in 2019. CPI-006 was designed to bind to an epitope on an antigen known as CD73. This antigen is known to be involved in lymphocyte migration and activation. CPI-006 binds to a distinct region of CD73 and behaves as an agonist that serves as a signal to activate certain immune cells. As previously reported, binding of CPI-006 affects B cells, T cells and antigen presenting cells. The collection of observed changes are consistent with enhanced antigen recognition and induction of an adaptive immune response.

About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company. 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 activation of immune cells. These product candidates are being studied in ongoing Phase 1b/2 and Phase 1/1b clinical trials in patients with a wide range of advanced solid tumors. Ciforadenant is being evaluated in a successive expansion cohort Phase 1b/2 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 pembrolizumab. The Company’s third cancer 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. The Company is also evaluating CPI-006 as a treatment for COVID-19 patients.  For more information, visit www.corvuspharma.com.

About CPI-006
CPI-006 is a potent humanized monoclonal antibody that reacts with a specific site on CD73. 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 in development for treatment of cancer, such antibodies have been reported to react with a different region of CD73 and are designed to block production of adenosine, which is not involved in the immunomodulatory processes seen with CPI-006. CPI-006 is in a Phase 1 study in patients with COVID-19 aimed at increasing anti-SARS-CoV-2 immune response.

Forward-Looking Statements
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of CPI-006, the Company’s ability to develop and advance product candidates into and successfully complete clinical trials, including the Company’s Phase 1 clinical trial of CPI-006 for COVID-19. 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 June 30, 2020, filed with the Securities and Exchange Commission on July 30, 2020, 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 CPI-006; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete 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 foreign countries; and the effects of COVID-19 on the Company’s clinical programs and business operations. 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
W2O pure
+1-213-262-9390
sseapy@purecommunications.com

Source: Corvus Pharmaceuticals, Inc.