New Data from Corvus Phase 1 Study of CPI-006 Continues to Support its Potential as a Treatment for COVID-19
Enrollment in first three cohorts complete; final cohort now enrolling with plans to initiate a pivotal study before year-end
Data continues to support the novel immunotherapy based on B cell activation with CPI-006, including the inducement of sustained high titers of SARS-CoV-2 specific antibodies and increased levels of memory B cells
Dose-response effect seen in first two cohorts with prolonged high titers of antibodies observed out to 56 days; additional data expected to be presented at SITC meeting in November
Corvus hosting conference call today at 8:30 a.m. ET /
These results build on the initial data from the first two cohorts (0.3 mg and 1.0 mg doses) of the study that was published online at medRxiv.org in
To-date, the first three cohorts of the study have been enrolled and the final cohort is currently enrolling patients. A new study site,
“We continue to see consistent, promising results with CPI-006 in hospitalized COVID-19 patients,” said
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.
In the first three cohorts of the study, the median age of the patients was 63 years (range 26-76 years) and 12 of 15 patients are minorities at higher risk for COVID-19 disease complications (7
- 14 of 14 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 all evaluable patients within 7 days of a single infusion of CPI-006. As previously reported, 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 as of
September 28, 2020.
- In 11 of 11 patients with serum samples available to be tested, the combined IgG and IgM antibody responses continued to increase out to 28 days post treatment with CPI-006 as of
September 28, 2020, in-line with the prior study data.
- In three of three patients tested, memory B cells, and memory CD4 and CD8 T effector memory cells, increased at 28 days post-treatment, and for one of such patients, memory B cells increased from 1.8% to 7.9% of B cells at 56 days post-treatment.
- As of
September 28, 2020, 14 of 15 patients were discharged from the hospital with clinical improvement after a median of 4.5 days. One patient remains in the hospital with improvement of symptoms.
- There have been no drug-related toxicity or safety issues reported.
Dose-Response Observed in Cohort 1 and Cohort 2
The 28-day and 56-day anti-SARS-CoV-2 antibody data for patients receiving 0.3 mg/kg (cohort 1) and 1.0 mg/kg (cohort 2) doses showed a dose-response with higher and more prolonged titers observed in the 1.0 mg/kg cohort compared to the 0.3 mg/kg cohort (see charts below).
- IgG and IgM titers to trimeric spike and receptor binding domain (RBD) of SARS-CoV-2 were measured and compared to convalescent serum obtained from recovered COVID-19 patients.
- Geometric mean titers (and range) were evaluated and revealed robust response at 28 days for both cohorts with higher and more sustained levels at day 56 seen in the 1.0 mg cohort. For example, day 56 IgG to spike protein titer was 49,519 as compared to 204,800 in patients receiving 0.3 and 1.0 mg/kg, respectively. Day 56 titers to RBD were 37,286 as compared to 144,815 in patients receiving 0.3 and 1.0 mg/kg, respectively.
- Sustained and high IgM titers were also observed and exhibited a similar dose-response.
A figure accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/2c5d507a-3dd3-4bf8-bc24-648aa345512c
Anti-SARS-CoV-2 antibody response (IgG and IgM) to spike protein and RBD of SARS-CoV-2. Patients receive 0.3 or 1.0 mg/kg single dose of CPI-006 and antibody titers measured at pre-treatment and at Days 28 and 56. Data are shown as box and whisker plot with geometric mean and interquartile ranges.
Background Information on CPI-006 for the Treatment of COVID-19
Corvus is studying an immunostimulatory humanized monoclonal antibody, designated as CPI-006, which the Company believes 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, and increased levels of both memory CD4+ and CD8+ 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’ Phase 1/1b study demonstrated that CPI-006 was 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 is designed to bind to a distinct region of CD73 and behaves as an agonist that serves as a signal to activate certain immune cells in preclinical studies. As previously reported, binding of CPI-006 affects B cells, T cells and antigen presenting cells. The collection of observed changes were consistent with enhanced antigen recognition and induction of an adaptive immune response.
CPI-818 Phase 1 Study
The Company also announced that it plans to present data at the
Conference Call Details
The Company will discuss the updated data from the CPI-006 COVID-19 Phase 1 study in a conference call and webcast today,
About Corvus Pharmaceuticals
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 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 currently being evaluated in an ongoing Phase 1 study in patients with COVID-19 and has demonstrated enhanced antibody responses to the SARS-CoV-2 virus.
CPI-818 is a small molecule drug given orally that has been shown to selectively inhibit ITK (interleukin-2-inducible T-cell kinase). It was developed to possess dual properties: to block malignant T-cell growth and modulate immune responses. ITK, an enzyme, is expressed predominantly in T-cells and plays a role in T-cell and natural killer (NK) cell lymphomas and leukemias, as well as in normal immune function. Interference with ITK signaling can modulate immune responses to various antigens. The inhibition of specific molecular targets in T-cells may be of therapeutic benefit for patients with T-cell lymphomas and in patients with autoimmune diseases. The Company is conducting a Phase 1 dose escalation trial in patients with refractory T-cell lymphomas.
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.
Chief Financial Officer
Source: Corvus Pharmaceuticals, Inc.