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 to recover from a SARS-CoV-2 infection in the US.
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 individuals, such as people with compromised immune systems, and medical workers who face frequent exposure to the virus.
Lilly’s program is one of about two dozen programs 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 it expects results by the end of June and that it will begin a larger Phase II trial soon thereafter 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 on Feb. 25, when AbCellera received a plasma sample obtained from a person who was infected with SARS-CoV-2 and had since 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 that target 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 big enough to hold a single B cell. As a solution of cells is flushed through the chip, B cells are corralled into their individual chambers. The company then looks for ones that make antibodies that bind the spike protein based on a glowing reaction in individual 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. One of them will likely be 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.
Several other drug firms and academic groups are also developing COVID-19 therapies using antibodies isolated from people who have recovered from a SARS-CoV-2 infection.
Regeneron is making antibodies from mice that have been genetically engineered to have humanized immune systems. The company is essentially vaccinating the mice with SARS-COV-2 spike proteins and isolating antibodies that neutralize the virus, which it will then mass produce.
Vir is making two versions of a monoclonal antibody that was originally isolated from a person infected with the original SARS-CoV virus. The firm says the antibodies neutralize both SARS-CoV and SARS-CoV-2. Vir is working with Biogen to manufacture the antibodies.
AbCellera’s COVID-19 antibody program has helped the company attract funding and the impact will outlast the current pandemic. In early May, the Canadian government committed about $129 million to the firm. And at the end of May, AbCellera raised $105 million in series B financing from several sources, including Lilly, the venture capital firm OrbiMed, and the entrepreneur and investor Peter Thiel. AbCellera will use the money to expand its drug-discovery work, open a 4,500 m2 lab, and build a manufacturing facility to produce its experimental therapies for clinical trials.
Two years before the pandemic, AbCellera was selected as one of four participants in a US challenge to rapidly discover and manufacture antibody therapies for emerging infectious diseases. The goal of the 4-year challenge, sponsored by the US Defense Advanced Research Projects Agency, was to develop field-ready therapies 60 days after identifying a new pathogen.
In March, DARPA program director Amy Jenkins told C&EN that the four groups were getting ready for a new trial run in January when SARS-CoV-2 began to spread. Like the others, AbCellera decided to put its practice to the test by developing the antibody that Lilly is now testing in humans.