Eli Lilly and Co. said June 1 the first patients have been dosed in a phase I test of LY-CoV555, a potential antibody treatment for COVID-19, with results expected by June 30. Should it prove safe, the candidate could quickly move into a phase II trial to assess its efficacy, Ajay Nirula, vice president of immunology at Lilly, told BioWorld. The news follows Lilly's May 4 announcement of efforts to co-develop antibodies for the prevention and treatment of the infection with Shanghai Junshi Biosciences Ltd. and testing of its already-marketed small-molecule JAK inhibitor, Olumiant (baricitinib), as part of the NIH-led adaptive COVID-19 treatment trial.

The new candidate, a neutralizing IgG1 monoclonal antibody directed against the spike protein of SARS-CoV-2, is the first to emerge from Lilly's collaboration with Abcellera Biologics Inc., a deal that itself was just signed in early March. Under the terms of the agreement, Abcellera and Lilly committed to equally share initial development costs toward a product, after which Lilly will be responsible for all further development, manufacturing and distribution work and costs.

Ajay Nirula, vice president of immunology, Eli Lilly

Lilly's work joins significant efforts underway at Regeneron Pharmaceuticals Inc., Roche Holding AG, Vir Biotechnology Inc., Celltrion Inc. and academic institutions such as the University of Toronto, all of which are pursuing the development of antibody therapeutics for the virus. Though the Regeneron and Roche programs have already entered the clinic, clinical testing of LY-CoV555 appears to be the first clinical effort to evaluate an antibody specifically designed to block SARS-CoV-2's attachment and entry into human cells.

The candidate was generated in just three months after Abcellera and the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases identified it from a blood sample taken from one of the first U.S. patients who recovered from COVID-19.

Vancouver, British Columbia-based Abcellera's high-throughput microfluidics platform, adapted through the Defense Advanced Research Projects Agency's Pandemic Prevention Program for rapid response to pandemics, employs machine vision and artificial intelligence to identify immune cells and the exact sequences of antibodies they create. In this case, Lilly analyzed antibodies from the recovered patient, characterizing close to 500 of them to understand which ones were most potent at blocking SARS-CoV-2. In vitro and other testing helped narrow the scope even further before the company moved to generate a version of the most promising one for testing in the new phase I study.

The placebo-controlled trial, called J2W-MC-PYAA, is likely to enroll about 30 hospitalized COVID-19 patients. The key goals are to understand the safety and tolerability of the antibody, the pharmacokinetics that can guide dosing. But investigators, who started dosing patients Friday at the NYU Grossman School of Medicine and Cedars-Sinai in Los Angeles, will also help Lilly look at exploratory efficacy endpoints, such as measures of patient viral loads.

While Lilly is initially focused on testing LY-CoV555 in hospitalized patients, "ultimately, we want to branch out the program into different patient populations," Nirula said. The team is also interested in moving into other trials where they would study patients before they're hospitalized to see if administration of a therapeutic antibody earlier in the course of the disease could prevent progression to hospitalization or even play a prophylactic role. Such studies could be underway "in the relatively near future," he said.

Further potential studies could explore whether an antibody might be effective in combination with other medicines, such as Gilead Sciences Inc.'s remdesivir.

Later this month, Lilly's team will review the results of the phase I study of LY-CoV555 before potentially starting broader efficacy trials. But, in an illustration of the substantial urgency Lilly and other drugmakers see in the market, the Indianapolis company is also starting large-scale manufacturing of the potential therapy, it said.

"If LY-CoV555 becomes part of the near-term solution for COVID-19, we want to be ready to deliver it to patients as quickly as possible, with the goal of having several hundred thousand doses available by the end of the year," said Daniel Skovronsky, Lilly's chief scientific officer and president of Lilly Research Laboratories.

Meanwhile, together with Junshi Biosciences, Lilly is expected to file an IND and initiate clinical trials in the U.S. and China in the second quarter. That program, recently documented in an article in Nature, is also employing antibodies isolated from a recovered COVID-19 patient.

Lilly shares (NYSE:LLY) moved little on June 1, losing 50 cents to close at $152.45.

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