Last January, Netflix premiered the docuseries Pandemic: How to Prevent an Outbreak. Under normal circumstances, it might’ve been of interest to a relatively niche audience. But at the time, it was becoming clear that the novel coronavirus had not been sufficiently contained in China and that without proper and enforced guidelines and protocols from other countries, the world was staring down a devastating public health crisis. Pandemic spent 12 days in the Netflix top 10 in the United States last March.
Fast forward to today—with more than 105 million cases of COVID-19 and well over 2 million deaths globally—and rewatching Pandemic feels like a fever dream of shoulda, woulda, coulda, didn’t.
“You see that the countries that took it really seriously early did well: South Korea, New Zealand, Australia,” says Dr. Jacob Glanville, founder and CEO of the therapeutics company Centivax and one of the scientists profiled in Pandemic. “That indicates the importance of centralized leadership and policies in being able to contain this thing. And that’s something we need to think about very carefully in 2021.”
Even with a number of vaccines approved and being distributed, what Glanville wants more people to think about in 2021—most importantly, government and health officials—is antibody therapy.
Antibody therapy is meant to treat a patient who’s already sick by using a molecule to neutralize the virus, whereas a vaccine is a preventative measure to mitigate the risk of contracting the virus in the first place. Glanville acknowledges that both approaches are vital in the case of mitigating the pandemic stemming from a virus as infectious as SARS-CoV-2. But since March, the prevailing conversation—and the bulk of funding—has been around developing a vaccine.
“Nobody knew what the hell a monoclonal antibody therapeutic was a year ago. Everybody knows what a vaccine is,” Glanville says. “The problem is not enough people are going to receive a vaccine.”
Since vaccine distribution began in December, more than 35 million doses have been administered in the United States, reaching 8.4% of the total population. Aggressive measures to rollout out the two primary vaccines from Pfizer and Moderna are indeed underway (to varying degrees of success). But experts say to achieve herd immunity, 70% to 80% of people would need to get vaccinated—a number that becomes more difficult to hit as the virus mutates and becomes increasingly resistant, not to mention rampant skepticism of the vaccine itself and the still cumbersome measure of having to take multiple doses that could wear off over time.
In conjunction with the vaccine, antibody therapy is being seen as a viable option to address the overwhelming number of people already affected with the virus, which Glanville was surprised wasn’t top of mind for leading health officials at the onset of the pandemic. “It is unclear to me why the government spent so much money on so many different groups for vaccines, but gave all their money to two corporations for antibody therapies [Lilly and Regeneron],” says Glanville.
In November, the FDA issued an emergency authorization for monoclonal antibodies treatments. And clinical trials are indeed showing promising results.
However, Glanville thinks he has a more convenient and cost-effective approach that could disrupt COVID-19 treatments.
‘WE’RE GOING TO DO THIS ANYWAY.’
In Pandemic, Glanville and his team were attempting to create a universal flu vaccine, and their work showed promise with successful trials in pigs and earned a grant from the Bill & Melinda Gates Foundation. And while they’re allocating resources toward a universal COVID-19 vaccine, Glanville says that his immediate focus last January was on antibody therapy, i.e. utilizing the antibodies from the SARS-CoV virus (aka SARS) and adapting them to better recognize SARS-CoV-2.
“Those antibodies have already had years of research on them that show that they can bind SARS. They neutralize SARS. They protect animals from SARS,” he says. “So we can adapt those same working drugs to then work on the novel coronavirus.”
Glanville presented his approach to the Defense Advanced Research Projects Agency (DARPA) in early 2020. “[They were] like, this looks cool, but we’ve already given our money to somebody else,” he recalls. “And I decided, you know what? Fuck it. We’re going to do this anyway.”
Recently, Glanville’s efforts were bolstered by a $104 million acquisition from pharmaceutical company Charles River Laboratories in January.
Centivax’s approach to antibody therapy is distinct in two ways: First, Glanville says they’ve been able to concentrate their antibodies to the point where it can be administered in a shot as opposed to Lilly and Regeneron’s treatments that must be given through an IV.
“The problem is, if you get sick, you call the hospital and you say, ‘I need an IV.’ Anyone who can give you an IV is busy dealing with more sick patients. So you’re triaged out,” he says. With Centivax’s injectable version, a patient could go to a clinic or even a pharmacy for their shot, easing the burden on overtaxed hospitals.
Second, Glanville and his team have managed to turn off an antibody’s ability to cause an inflammatory response that often leaves patients feeling far worse than before a treatment. “Antibodies bind to the virus to neutralize it,” Glanville says. “But the problem is antibodies also recruit your immune system cells to go freak out at whatever they’re binding to, releasing danger signals called cytokines. They create local inflammation of tissue, and they will even attack.”
Normally, that’s a manageable enough scenario if the attack is on a non-vital organ. However, SARS-CoV-2 has been shown to bind 10 to 20 times more strongly than SARS-CoV and can attack multiple parts of the body.
“It’s like when you go hiking and burrs get stuck all over your socks. It’s like that on your heart tissue; it’s on your nerves, it’s on your lungs,” Glanville says. “It’s hard for your immune system to tease out just the virus without accidentally attacking the tissues as well. For all those reasons, my feeling was to turn off the effector functions.”
‘A GAME CHANGER’
Glanville says he won’t have a firm grasp on the true efficacy of his approach until he completes phase two of his study in mid-to-late summer this year.
“We’re relatively confident we’re going to be the ones that have the medicine that can actually work in a hospital, which would be a game changer,” he says.
Also part of his disruptive strategy is to make antibody therapy affordable.
The Trump administration paid Lily $375 million for 300,000 doses of its antibody drug, which boils down to $1,250 per dose.
Glanville estimates that Centivax’s version would only be $900 per dose, and, he says, it’ll cost even less with government support.
Lilly and Regeneron were testing 2.8 grams and 8 grams, respectively, per patient of their IV antibodies in their studies. “That’s a lot,” Glanville says. “But if you can give an injection early on, right when you first get sick, you can give like half a gram or a gram. So you can make more doses. You can make a life-saving medicine for less than the cost of an iPhone and make it routinely available outside of a hospital.”
Glanville estimates the United States would need 30,000 to 60,000 doses per month, with the rest of the world needing five times that. But he believes that’s totally doable by making the drug easy to use, accessible, and by driving down the cost per dosage. “There now is an opportunity to go start mass manufacturing these kinds of medicines,” Glanville continues, “and make them less expensive so it’s more accessible to the world.”