Eli Lilly and Company is the first company to begin a clinical trial of a monoclonal antibody that targets SARS-CoV-2, the novel coronavirus that causes COVID-19. AbCellera, an antibody start-up in Vancouver, British Columbia, led the discovery of the antibody, which was isolated from one of the first people in the US to recover from a SARS-CoV-2 infection.
The discovery effort began at the end of February. Now, just 3 months later, Lilly says it has given the experimental antibody, called LY-CoV555, to the first participants in a Phase I clinical study of people hospitalized with COVID-19. The trial began more than a month ahead of the companies’ earlier goal of late July.
The 90-day turnaround from discovery to injection is likely a record for monoclonal antibody drug development. LY-CoV555 may also be the first experimental drug designed after the discovery of SARS-CoV-2 to be tested as a treatment for COVID-19. The dozens of therapies already tested in COVID-19 patients—including remdesivir, an antiviral made by Gilead Sciences—were discovered before the pandemic and are now being repurposed to fight the coronavirus.
LY-CoV555 targets the spike protein of SARS-CoV-2 and in preclinical studies prevented the virus from infecting human cells. Scientists hope that mass-producing these antibodies will help clear the virus from people who are already infected and struggling to recover. Antibodies could also be given to healthy people to help prevent an infection for a few weeks or months. That prophylactic approach could prove useful for high-risk people, including those with compromised immune systems and medical workers who face frequent exposure to the virus.
Lilly’s program is one of about two dozen underway to develop monoclonal antibodies that target SARS-CoV-2. Several other firms, including Regeneron and Vir Biotechnology, expect to begin clinical trials of their antibodies in June or July.
The main goal of Lilly’s Phase I clinical trial is to see if LY-CoV555 is safe, but the company is taking the unusual step of including a placebo group in the study. That could provide early signs of whether the drug is working. Lilly says that it expects results by the end of June and that it will begin a larger, Phase II trial soon after if the drug appears safe.
Lilly has already begun large-scale manufacturing and is working on having several hundred thousand doses ready by the end of the year.
The discovery effort began Feb. 25, when AbCellera received a plasma sample obtained from a person who had been infected with SARS-CoV-2 and had recovered. That plasma contained precious B cells—the antibody factories of our immune systems. AbCellera scanned through more than 5 million B cells to find ones that made antibodies targeting the SARS-CoV-2 spike protein.
AbCellera conducted the screening in a matter of days. The company has developed credit card–sized microfluidic chips that contain 200,000 tiny chambers, each just big enough to hold a single B cell. As a solution of cells is flushed through the chip, B cells are corralled into individual chambers. A glowing reaction indicates the presence of antibodies that bind the spike protein, and points scientists toward those chambers.
Within 9 days, AbCellera had picked 500 antibodies to study further. Lilly and AbCellera narrowed the list to 190 candidates by mid-March. At that point, the companies collaborated with scientists at the Vaccine Research Center of the US National Institute of Allergy and Infectious Diseases to test the potency of the antibodies in preclinical experiments. The antibody now known as LY-CoV555 was one of the best.
Lilly says it may test additional antibodies in upcoming clinical trials, including an antibody called JS016 from the firm’s collaboration with Shanghai-based Junshi Biosciences. Clinical studies of JS016, which also targets the SARS-CoV-2 spike protein, are expected to begin in the US and China this month. Lilly may eventually combine both antibodies into a single experimental antibody cocktail. Many scientists believe that using two antibodies that target different regions of the spike protein will make it harder for the virus to mutate and evolve resistance to the drugs. Regeneron is developing an antibody cocktail to treat COVID-19, while Vir is developing two versions of the same antibody, engineered for different purposes.
Two years before the pandemic, AbCellera was selected to participate in a US challenge to rapidly discover and manufacture antibody therapies for emerging infectious diseases. The goal of the 4-year challenge was to develop field-ready therapies 60 days after identifying a new pathogen.
AbCellera was getting ready for a new trial run in January when SARS-CoV-2 began to spread. The company decided to put its practice to the test by developing the antibody that Lilly is now testing in humans.