When I read back in mid-March that the biotech firm Regeneron had isolated “hundreds of neutralizing antibodies against the SARS-CoV-2 virus,” I thought it sounded crazy. Antibodies, after all, are the immune system’s hound dogs, trained to recognize and attack any viral or microbial invader.
Even though the roughly 30-year-old company has previously developed a three-antibody drug to treat Ebola, I couldn’t understand how so many potential treatments could be isolated in a matter of weeks by a single entity. So I hopped on the phone March 23 with George Yancopoulos, the company’s co-founder, president and chief scientific officer. He spoke from his car, and I hoped he was driving slower than he talked. This conversation has been lightly edited for brevity.
Q: Are you in the back of a limousine?
A: I’m driving my five-year-old Nissan Altima. I do have Bluetooth so I’m talking hands-free. I’m doing my best to get my daughter’s friend a test as soon as possible. It’s just as hard for us as it is for everyone else. If I can get a test, I can go swab her.
Q: So how does one develop hundreds of drug candidates in a matter of weeks?
A: It depends a lot on automation. Our drug candidates are antibodies. Did you see the movie I Am Legend? [Will Smith] is a physician-scientist in New York City and there’s a pandemic that breaks out and everyone in his family dies. He survives because his body made immune cells. While he’s fighting infected zombies by day, by night he’s trying to clone his own immune serum and testing them on these rats he has in the basement. Why do I bring it up? This has been known for over a hundred years. A guy named [Emil] von Behring got a Nobel Prize for showing that if you infect rabbits with diphtheria bacteria, most would die, but the rare survivors had something in them that he called antitoxin. If you inject that into virgin rabbits, they become resistant to diphtheria.
Up until relatively recently, companies were still using similar methods. There were horse farms where they would inject the horses with pathogens and then harvest the serum and inject it into humans. Well, we don’t depend on human samples. We don’t need to find the Will Smith. We did something that allows us to do it faster, easier and better.
I have to take some credit. It was the idea of a lonely graduate student in 1985. I imagined that you could take the immune system of a human being and put it into a mouse, and then with that mouse you could literally challenge it with any pathogen and the serum from any mouse survivors would be totally human. Unlike when von Behring was injecting horse serum, here you would be injecting pure human antibodies from these mice, these micro-humans. I had that idea in ’85, and as a company we spent 20 to 30 years turning that not only into a reality but perfecting it so we can do it better and faster.
Q: Are you still doing the actual laboratory work?
A: The guy who leads this effort is an incredible, heroic scientific genius. He’s about 30 years behind me, he went to Columbia University like I did, and he also comes from my part of Greece. His name is Christos Kyratsous. He came up with a treatment for the MERS coronavirus, and then for Ebola, and now he’s using it for the novel coronavirus.
Q: How do you get so many antibodies so quickly?
A: We can create a very large collection of antibodies against any target, in this case coronavirus, using hundreds of the humanized mice but also by taking antibodies from human survivors of COVID-19. We use what’s called an adjuvant to boost the effect of the antibody. In the end, we get literally thousands of specific antibodies. We collect the best couple of hundred most potent neutralizers that block the virus.
Q: What then?
A: Our goal is to select the best two. We’re going to put them in a cocktail. It’s sort of like using a cocktail of antiretrovirals against HIV. By April 15, we will choose the two most potent and begin scaling them up. We will hopefully, by June, have tens of thousands of doses for use in a clinical trial. By the end of summer, we expect to have hundreds of thousands of doses per month. If all goes well, by then we will have evidence that this thing could be useful and could be given to critical-care workers and people at risk, elderly people, kids with cystic fibrosis, and the like.
Q: Assuming it works, would that be a cure?
A: There will still be an enormous need for a vaccine. Ours will only protect you, each shot, for a month or a couple of months. It’s not going to provide permanent immunity. It’s not something you would give to a billion people. Luckily, there are a lot of companies who are real experts in the development of vaccines, but vaccines take a lot longer to go through the whole process. So this will be an interim treatment.
Somebody in China tested an anti-inflammatory drug that targets interleukin-6 (IL-6) for people in severe respiratory distress from COVID-19. They claimed in anecdotal uncontrolled data that the results were pretty spectacular. Now we have similar anecdotal stories coming in that some patients, particularly in Italy, have been treated with another IL-6 blocker, [sarilumab], that we developed with Sanofi. We announced a clinical trial for that a week ago, but it feels like a year ago. It’s a lot to keep track of. A study that would normally take six months for the FDA to approve took a few days. We submitted the first protocol around midnight last Saturday night. At 7:46 on Sunday evening, they gave us our final approval, and we initiated the program on Monday.
Q: How are you handling the stress?
A: Some of us are actually enjoying the pandemonium. It’s exciting to have the opportunity to rise to a challenge. It’s these times of stress where we can all go into decline and have a doomsday approach. But times of great challenge are times of great opportunity for humanity to show what we’re made of. I hope we don’t devolve. I hope we all rise to the challenge collectively and show who we are.