Benzinga | Oct 5, 2020 07:24AM EDT

Corvus Pharmaceuticals Announces Updated Data From Phase 1 Study Of CPI-006 In 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 830 a.m. ET / 5:30 a.m. PT

BURLINGAME, Calif., Oct. 05, 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 updated data includes 56-day follow-up results from the first two cohorts (0.3 mg/kg and 1.0mg/kg dose) and initial results from the third cohort (3.0 mg/kg) of the study. The 56-day follow-up results showed a dose-response, with higher and more prolonged titers of anti-SARS-CoV-2 antibodies in the 1.0 mg/kg cohort compared to the 0.3 mg/kg cohort. In addition, the results showed increased levels of memory B cells and memory T cells, and there have been no reports of any drug-related safety issues in any of the 15 patients treated as of September 17, 2020.

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 September 2020. In addition to detailing the initial results, the medRxiv manuscript provides additional details on the unique properties of CPI-006 and on the study rationale and design, along with context on the broad potential for CPI-006 for the treatment and prevention of COVID-19.

To-date, the first three cohorts of the study have been enrolled and the final cohort is currently enrolling patients. A new study site, El Centro Regional Medical Center in El Centro, CA, which is affiliated with the U.C. San Diego Health Care Network and serves Imperial and Riverside counties in southern California, has also begun enrolling patients. The Company continues to anticipate that it will complete the study and report results during the fourth quarter of 2020, including a presentation of data at the Society for Immunotherapy of Cancer (SITC) annual meeting in November. Based on these interim data, and assuming the remainder of the data in the study supports it, the Company plans to initiate a pivotal, randomized, double blind study in hospitalized COVID-19 patients before year-end.

"We continue to see consistent, promising results with CPI-006 in hospitalized COVID-19 patients," said Richard A. Miller, M.D., president and chief executive officer of Corvus. "The data indicates that B cell activation with CPI-006 stimulated robust and durable immune responses, and that these responses have been associated with induction of memory B and memory T cells. The dose-response observed in the first two cohorts support the proposed mechanism of action of the drug and provide evidence of induction of high levels of antibodies with relatively low doses of CPI-006. The data supports continued evaluation of CPI-006 in this patient population, and potentially in outpatients with COVID-19 and in other infectious diseases. We are also exploring the potential use in combination with preventative vaccines under development by third parties to enhance and prolong 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.

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 African American and 5 Latino). All of the patients had comorbidities that increased their COVID-19 risk including diabetes, hypertension, obesity, chronic lung disease and/or cancer. The median duration of symptoms prior to treatment with CPI-006 was 5 days (range 1-21 days). The key highlights from these 15 patients, beyond the data already reported from the first 10 patients in the medRxiv manuscript, include:

* 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 American Society of Hematology meeting in December on its Phase 1 dose escalation trial of CPI-818 in patients with refractory T-cell lymphomas, which would include information regarding the one complete remission (CR) and the one partial remission (PR) seen out of seven patients with peripheral T-cell lymphoma treated with CPI-818 as a single agent to date.

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, Monday, October 5, 2020, at 8:30 a.m. ET (5:30 a.m. PT). 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 13711371. The live webcast 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.