Benzinga | Nov 9, 2020 08:06AM EST

Corvus Reports Completion Of Enrollment In Phase 1 Study Of CPI-006 For Patients With COVID-19, Presents Study Data At 2020 Society For Immunotherapy For Cancer Meeting

Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company, today announced that it has completed patient enrollment in its Phase 1 study investigating the potential for CPI-006 to provide a novel immunotherapy approach for hospitalized patients with COVID-19. This novel immunotherapy may provide a therapeutic benefit from the activation of a polyclonal antibody response to the SARS-CoV-2 virus and the induction of long term immunity through active immunization. Updated data from the study is being presented this week in a poster presentation and an oral presentation at the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting. The oral presentation will take place on Friday, November 13 at 12:15 pm ET as part of Session 301, which is titled "Hot Topic Symposium: COVID-19 and Cancer." Based on the study data to-date, the Company plans to initiate a pivotal, randomized, double blind study of CPI-006 in hospitalized COVID-19 patients in December with results expected around mid-2021.

Lead investigator of the CPI-006 COVID-19 Phase 1 study, Gerard J. Criner, M.D., from Temple University Hospital, said, "The results to-date in the Phase 1 study of CPI-006 for the treatment of COVID-19 have been very encouraging. With relatively low doses of CPI-006, we have seen patients generate high levels of antibodies to the virus that continue to increase and are sustained over months. The data also suggests that these patients have increased memory B cells, which could produce long-term immunity. We look forward to further investigating the potential of CPI-006 as a novel immunotherapy for COVID-19 in a pivotal study that will begin enrolling patients by the end of the year."

The data presented at SITC include results from 22 patients enrolled in the Phase 1 study utilizing a cut-off date of November 4, 2020. This includes enrollment in all four dosing cohorts of the study (0.3, 1.0, 3.0 and 5.0 mg/kg). All patients received a single dose of CPI-006 administered via a 5-10 minute intravenous (IV) infusion. The median age of the patients was 58 years (range 23-76 years). All of the patients had comorbidities that increased their COVID-19 risk including diabetes, coronary disease, hypertension, obesity, chronic kidney disease, chronic lung disease and/or cancer. 95% of patients were from minority populations that are at high risk of COVID-19 complications. The key highlights from the presentation include:

Results Support the Immune Enhancing Role of CPI-006 in COVID-19

* All patients had relatively low titers of anti-SARS-CoV-2 antibodies at the time of hospitalization despite having varying durations of prior COVID-19 symptoms from 1-21 days (median 5 days); all patients had a confirmed COVID-19 diagnosis by positive PCR nasal swab testing.

* All evaluable patients had prompt anti-SARS-CoV-2 antibody responses within 7 days of administration of CPI-006 at all dose levels.

* All patients recovered and were discharged from the hospital at a median of 4 (range 2-23) days.

* As of the November 4, 2020 cut-off date, there were no drug-related toxicity or safety issues reported.

Antibody Response Results

* Four of four evaluable patients that received the 0.3 mg/kg dose had sustained high titers of IgG antibodies to trimeric spike (TS) protein out to 84+ days (one patient 100+ days), without evidence of diminution of response. In these patients, IgM antibody titers peaked at 28-56 days and remained elevated out to 84+ days. Similar trends were seen in IgG and IgM antibody response to receptor binding domain (RBD).

* The geometric mean titers (GMT) for the 0.3, 1.0 and 3.0 mg/kg cohorts are shown in the charts below. A dose response was observed comparing the 3.0 and 1.0 mg/kg dose to the 0.3 mg/kg dose. Higher and more sustained titers of both IgG and IgM to both spike protein and RBD were seen out to 56 days when comparing the 1.0 to 0.3 mg/kg doses. The IgM responses were noteworthy for the sustained prolonged elevation. Antibody responses from 3.0 and 5.0 mg/kg doses appeared similar to the 1.0 mg/kg dose, but the follow up period for such doses was shorter as of the cut-off date.

* In viral neutralization assays, three of three patients developed anti-viral antibody responses out to day 56 that blocked infectivity of receptor bearing cells in a pseudovirus neutralization assay.

* Memory B cells were elevated in 6 of 6 tested patients following treatment with CPI-006. Memory T effector cells were also elevated following treatment and produced interferon-gamma and interleukin-2 in response to SARS-CoV-2 antigen consistent with antigen specific Th1 biasing.

A graphic accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/7f7141d0-ea50-4293-8b5f-a4e3e8c420f6

Anti-SARS-COV-2 antibody response (IgG and IgM) to trimeric spike protein and RBD of SARS-CoV-2. Patients received a 0.3, 1.0 or 3.0 mg/kg single dose of CPI-006 and antibody titers were measured at pre-treatment and at days 28, 56 and 84. Data are shown as box and whisker plot with geometric mean and interquartile ranges. Each dot represents a patient. Also shown are titers from convalescent patients serum obtained 28-42 days after recovery from COVID-19.

Polyclonal Antibody Response

* The magnitude and diversity of the polyclonal responses were evaluated by mapping of antibody responses to the subdomains of the TS protein including the N-terminal, RBD, S1 and S2 subdomains. Polyclonality and reactivity to multiple antigenic determinants on the virus were found, which have the potential to lead to viral neutralization and elimination and to reduce the potential for escape due to emergence of mutant forms of the virus. The mapping shows: IgG responses were polyclonal, polyspecific and directed to all subdomains. IgM responses were polyclonal and directed to all subdomains but are preferentially directed to the RBD.

Preclinical Results from Humanized Mouse Studies

Vaccination studies conducted by Corvus in mice bearing human immune cells showed that administration of combinations of CPI-006 with TS protein from the SARS-CoV-2 virus resulted in an antigen specific humoral immune response to the TS protein. No humoral immune response was seen in mice receiving combinations of TS with a control antibody. The responses were specific to the immunizing TS protein as there was no reactivity to other viral proteins. These controlled studies demonstrated that the administration of CPI-006 led to the generation of antigen-specific immune response to the TS protein.

Update on CPI-006 Phase 1/1b Cancer Clinical Trial

Corvus announced that it has completed enrollment in the final cohort of the Phase 1/1b cancer clinical trial. This cohort was designed to evaluate CPI-006 in combination with ciforadenant, the Company's A2A receptor antagonist, and pembrolizumab (triplet cohort). Other cohorts examined CPI-006 monotherapy and in combination with ciforadenant (doublet cohort). Nine patients were enrolled in the triplet cohort, including four patients with renal cell cancer (RCC). All four RCC patients remain on treatment from 2-11+ months and results, as of the November 4, 2020 cut-off date, include one partial response (RECIST) in a patient refractory to previous treatment with nivolumab, ipilimumab and cabozantanib. This patient's tumor was positive for the Adenosine Gene Signature, a biomarker discovered by Corvus that reflects adenosine induced immunosuppression in the tumor. As of the cut-off date, the other three patients remain on study with stable disease.

"The updated COVID-19 patient data presented at SITC continues to provide evidence regarding the unique potential immunotherapy mechanism of CPI-006, which appears to drive a robust and durable humoral response to the SARS-CoV-2 virus," said Richard A. Miller, M.D., president and chief executive officer of Corvus. "Specifically, the immunobiology tells us that CPI-006 is activating antigen specific B cells, triggering the body's inherent immune response to generate durable, high titers of polyclonal antibodies to diverse antigenic determinants on the virus. This contrasts favorably to the passive monoclonal antibody programs currently being studied in patients, which require significantly higher doses and do not provide polyclonality, diversity or durably sustained antibody levels. Our data is consistent with a recent publication that reports shorter recovery times in patients that mount durable anti-SARS-CoV-2 antibody responses.1 Taken altogether, we have increasing confidence that CPI-006, if approved, could be a meaningful treatment for COVID-19, particularly as new cases are surging again."

"In addition, we believe these data suggest CPI-006, if approved, could have broader potential to treat outpatients with COVID-19, to be used in combination with preventative vaccines to enhance and prolong immunity, and for other infectious diseases. In parallel with our pivotal study, we will be exploring these potential applications and are working tirelessly in an effort to make CPI-006 available for the treatment and prevention of COVID-19," added Dr. Miller.



The results presented at SITC 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 provided 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.

1 Chen et al Cell. https://doi.org/10.1016/j.cell.2020.10.051

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. The study design is evaluating CPI-006 monotherapy and in combination with ciforadenant and combination with pembrolizumab. Another cohort of the study is evaluating the triplet of CPI-006, ciforadenant and pembrolizumab. As of the November 4, 2020 cut-off date, CPI-006 had 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 the administration of CPI-006 was associated with increased 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.

R&D Symposium Conference Call, Webcast and Presentation Slides

Corvus will host an R&D Symposium on November 12, 2020, from 11:00 am - 1:00 pm ET (8:00 - 10:00 am PT), to highlight the COVID-19 program data and provide updates on its cancer programs. The R&D Symposium will be hosted by Dr. Miller and other members of the Corvus team. The agenda includes the following guest speakers:

* Tullia C. Bruno, PhD, Assistant Professor, Department of Immunology at UPMC Hillman Cancer Center. Dr. Bruno will provide an overview of B cell biology and antibodies.

* Gerard J. Criner, M.D., Chair and Professor, lead investigator of the CPI-006 COVID-19 Phase 1 study, and Chair and Professor, Thoracic Medicine and Surgery at the Lewis Katz School of Medicine at Temple University. Dr. Criner will provide an overview of current COVID-19 therapies and results from the CPI-006 COVID-19 Phase 1 study.

Members of the Corvus team will provide an overview of the preclinical biology and data on CPI-006, plans for the CPI-006 pivotal study for patients with COVID-19, and a general pipeline update covering the Company's cancer programs. The speakers will be available for questions and answers during the program.

The R&D Symposium conference call can be accessed by dialing 1-877-423-9813 (toll-free domestic) or 1-201-689-8573 (international) and using the conference ID 13712583. 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.