Candidate: Mupadolimab (formerly CPI-006)
Type: Agonistic (immunostimulatory) humanized monoclonal antibody designed to bind to an epitope on CD73, an antigen known to be involved in lymphocyte migration and activation.
2021 Status: DEVELOPMENT ENDS IN COVID-19—Corvus said July 15 it had halted a Phase III trial (NCT04734873) assessing mupadolimab for COVID-19 and ending development of the antibody against SARS-CoV-2, citing “positive trends exhibited by COVID-19 vaccines in lowering serious infection and hospitalizations.” The company insisted its decision to discontinue the trial was not related to any safety or efficacy issues observed in study patients.
Instead, Corvus said, it is continuing a Phase I/Ib trial (NCT03454451) of mupadolimab in a variety of advanced cancers: “We are prioritizing resources on mupadolimab in oncology and intensifying our efforts in our cancer programs,” stated Richard A. Miller, MD, Corvus’ co-founder, President and CEO.
2020 Status: Corvus said November 10 it planned to launch a pivotal, randomized, double blind study of CPI-006 in hospitalized COVID-19 patients in December, with results expected around mid-2021. The decision followed positive data as of that date from the company’s Phase I trial (NCT04464395) investigating the potential for CPI-006 to provide a novel immunotherapy approach for hospitalized patients with COVID-19.
In a poster presentation and an oral presentation at the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting, held November 13, Corvus presented data from 22 patients enrolled in the Phase I study through the November 4 cutoff date. The 22 patients were enrolled in all four dosing cohorts of the study (0.3, 1.0, 3.0 and 5.0 mg/kg).
All four evaluable patients receiving the 0.3 mg/kg dose had sustained high titers of IgG antibodies to trimeric spike protein out to 84+ days (100+ days for one of the patients), without evidence of diminution of response. In these patients, IgM antibody titers peaked at 28-56 days and remained elevated out to 84+ days. Also, a dose response was observed comparing the 3.0 and 1.0 mg/kg dose to the 0.3 mg/kg dose. 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.
All patients received a single dose of CPI-006 administered via a 5-10 minute intravenous (IV) infusion. 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. Nearly all patients (95%) were from minority populations at high risk of COVID-19 complications.
On September 10, Corvus announced updated data from its Phase I trial (NCT04464395) for CPI-006 showing that all evaluable patients in its first two cohorts 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. The cohrts consisted of five patients receiving an 0.3 mg dose and five receiving a 1.0 mg dose. In all patients evaluated, the antibody responses continued to increase out to 28 days post treatment with CPI-006.
Serum immunoglobulin (IgG and IgM) antibody titers against the SARS-CoV-2 trimeric spike and/or receptor binding domain (RBD) increased in all eight evaluable patients within seven days of a single infusion of low doses of CPI-006. The study’s primary efficacy endpoint is the change in IgM and IgG anti-SARS-CoV-2 levels compared to baseline at day 28.
Another patient did not have a pre-treatment serum sample available but had a sample collected one day after receiving CPI-006 which exhibited a high titer that continued to increase, Corvus said.
Corvus said it has submitted a manuscript detailing the initial results for publication online at medRxiv.org.
The Phase I trial was launched July 7, wth the aim of assessing CPI-006’s novel immunotherapy approach in patients with mild to moderate COVID-19. The open-label, Phase I study is expected to enroll up to 30 patients at several U.S. sites who 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.
According to Corvus, CPI-006 has shown 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, based on in vitro and in vivo studies in cancer patients. CPI-006 has also led to increased levels of memory B cells.
Corvus asserted that CPI-006’s 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.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: