With research collaborations being formed right and left to develop antibodies that can neutralize SARS-CoV-2, the virus that causes COVID-19, scientists have started raising concerns about the potential efficacy of the planned therapies. Most of the antibodies under development target the virus’s spike protein, which facilitates its infection of healthy cells. But naysayers worry that the virus will find a way to get around those antibodies.
Sorrento Therapeutics has a plan for addressing that concern: Instead of targeting just one point on the spike protein, it will invent an antibody cocktail that binds to three different “epitopes,” or regions of it. It has teamed up with scientists at Mount Sinai Health System in New York to develop the treatment, the company announced today.
“If one epitope mutates and one of the antibodies does not do its job anymore, the other two can do the job,” Henry Ji, Ph.D., CEO of Sorrento, told FierceBiotechResearch. “They are synergistic.”
The therapy, which Sorrento has dubbed COVI-SHIELD, started with a diagnostic test developed at Mount Sinai that was used to screen 15,000 people who were believed to have recovered from COVID-19. Sorrento’s scientists are using those samples to identify a few dozen antibodies that stand the best chance of being able to completely neutralize SARS-CoV-2, Ji said.
Sorrento will then work with scientists at the University of Texas Medical Branch, who will test the antibodies against the live virus. “We’re looking for 100% total inhibition of viral infection,” Ji said. Once the top few contenders are selected, Sorrento will work with Mount Sinai to further analyze them.
Mount Sinai may also serve as a clinical testing site for COVI-SHIELD, which the company aims to move into phase 1 trials in the third quarter.
Sorrento joins a rapidly growing crowd of companies working on neutralizing antibodies to defeat COVID-19. Monday, Eli Lilly paid $10 million upfront to China’s Junshi Biosciences for the right to co-develop and market a fully human monoclonal antibody against the virus.
Regeneron, which is widely considered the front-runner in this race, has identified two neutralizing antibodies it plans to test in combination for treating COVID-19 as early as June.
Still, neutralizing antibodies pose a risk of backfiring in a process called antibody-dependent enhancement (ADE), whereby the virus uses the antibodies to ramp up the infection. Regeneron addressed that concern during an earnings conference call earlier this week, expressing confidence that its experimental COVID-19 antibody cocktail would sidestep ADE by targeting “uber stealth constant regions” of the virus.
Sorrento is engineering its antibodies so they cannot bind to the receptor on immune cells that’s believed to cause ADE. They also plan to select antibodies that have different mechanisms for neutralizing SARS-CoV-2 in hopes of reducing the chances of patients becoming resistant to the treatments, Robert Allen, vice president of antiviral and oncolytic immunotherapy development for Sorrento, told FierceBiotechResearch.
“Some of them are going to neutralize through direct blocking between spike and ACE2,” the receptor that helps the virus infect human cells, Allen said. “Others are going to neutralize through a non-blocking mechanism. We’re able to create a higher barrier to resistance that way.”
Sorrento is embarking on its COVID-19 research venture just months after dodging a takeover bid by a private equity firm. In January, the company disclosed it had received a buyout bid at $7 a share—more than twice its trading price at the time—but the board decided the offer wasn’t good enough. The company’s shares are now trading around $2.41 as it works with limited resources to advance its pipeline of CAR-T cancer treatments and pain drugs.
Despite the mounting competition in COVID-19, Ji is confident Sorrento and its academic collaborators will be able to work quickly to discover an effective cocktail of neutralizing antibodies. “The Mount Sinai collaboration is very important for us, because they screened 15,000 samples and picked the highest-protected people,” Ji said. “We expect to be able isolate very potent antibodies.”
That said, Ji is well aware that Sorrento and all of its rivals have a lot of work to do before their COVID-19 treatments will be ready for clinical testing. “We don’t know which of these antibodies will be useful. Maybe some of them, maybe none,” he said. “Whoever has the best antibody wins.”