Regeneron Co-Founder on Monoclonal Antibody Treatment

[MUSIC PLAYING] We've spent a lot of time talking about vaccines and rightfully so since that's the most effective way to quash the pandemic. At the same time, though, we're also developing therapeutics to treat COVID. One area that has shown considerable success are monoclonal antibodies.

Clinical trials show that monoclonal antibody treatment, actually a combination of two antibodies, reduces COVID-19 related hospitalization or deaths in high-risk patients by about 70%. And when given to an exposed person, like someone living with an infected person, monoclonal antibodies reduced their risk of developing an infection with symptoms by 80%.

There has been tremendous development just in the last couple of months in terms of exactly who qualifies and when, as well as how they're given. I had the opportunity to sit down with Dr. George Yancopoulos, Co-founder, President, and Chief Scientific Officer for Regeneron Pharmaceuticals, to talk about why they decided to invest in research in monoclonals, what their research shows about their use, as well as what the COVID pandemic has taught him personally and professionally. George, thanks for joining me today.

Sure. It's a pleasure.

Now I want to start off with everyone's talking about the vaccines and rightfully so. But Regeneron decided to focus on therapeutics. Can you walk us through that reasoning?

Well, there's so much need for so many approaches to fight back against this pandemic. And you do what your technologies allow you to do. We had spent decades developing some of the world's best technology to create antibodies against almost any target. We had uses to fight an assortment of different diseases, including recently and relatively successfully Ebola.

So we realized while there was a lot of efforts on vaccines, and as you said, vaccines are absolutely essential to try and create immunity within the population. As we're seeing now, despite the vaccines, there's the potential for there to still be a lot of disease burden. And there will also be people, such as the immunocompromised, who will never respond to vaccines. So we reasoned that there would be a great need to provide what it is that vaccines try to generate. Vaccines try to generate antibodies in people.

Well, some people can't generate those antibodies, for some people, they're not vaccinated, for some people, it's too late. So for those people, we reason we could make those antibodies, give them back to these people, and we had developed the technologies. We had invested decades and decades into technologies that could optimize the approach for rapidly generating the best of antibodies. So we chose to do what we could do to complement what was going on in the rest of the world.

And can you explain for our audience what monoclonal antibodies do because it can be confusing. We refer to them as monoclonal, sometimes polyclonal. We use the word cocktail. At the simple level, what does your technology do?

Well, the important thing is to understand what antibodies are. Antibodies are what the body uses to fight back against disease. They can literally bind viruses such as the SARS-CoV-2 virus that causes COVID-19. They can bind it. They can block it. Keep it from being able to infect human cells. And also help clear, it help remove it.

When the body makes antibodies, it makes hundreds of different kinds of antibodies, not all of them are all that effective. We've established technology to make exactly the sort of antibodies that the body normally makes. We can make them outside of the body. We can test them and take the best antibodies, the ones that are best at binding the virus, blocking it, neutralizing it, and then putting them together in a cocktail.

So we chose two of the most effective antibodies that we could find against the hundreds that the body can normally make, putting them together in a cocktail, a mixture of two antibodies that had the greatest power to bind, neutralize, and protect against the virus. But also the way we select them was in a way that we predicted based on a lot of evidence, a lot of preclinical evidence, a lot of studies in Petri dishes, but also in animals, that these antibodies would be able to protect against variants that might emerge.

We even predicted some of the exact variants that we have now been seeing that we're worried about. And we predicted that this cocktail that we have put together, of two of the best possible antibodies that we could generate, could actually, not only bind and neutralize and protect against the original SARS-CoV-2 virus, but we predicted it could withstand a lot of these variations that are occurring. And to date, that's been the case.

And that's a good point, because we've been talking about whether these protect against the variants, including the Delta variant. And research has shown that it does. I do want to talk about some recent findings, a recent expansion of authorization for post-exposure prophylaxis.

So we first talked about giving monoclonal antibodies early on to certain patients. And first, I have to say in terms of language, post-exposure prophylaxis. When we're trying to explain that to patients, we've been trying to explain it to clinical colleagues. What exactly does that mean? And I'm going to be honest, George, why does it have to be so difficult in terms of a language? Because we're really using it for prevention for some people, but we're not using that term.

Well, as you said, the nomenclature is complicated. It's complicated even to me. I'm not sure I understand why the rationale and the reasoning for all these words. But as you said, initially, our authorization was for people who were already infected. And for those high-risk people who had a high chance of progressing from being infected to becoming very sick, hospitalized, and maybe even dying, we had an authorization to give it to these patients in the data set as early as possible was the better and we could prevent by more than 70% hospitalization and death in these early infected individuals.

The most recent authorization is for prevention. And it's for a limited degree of prevention. It's for people who have either already had a high risk exposure. That is, they were in close contact with somebody who had COVID-19. So they're at risk of developing COVID-19 and they don't have it yet, or they are at risk of coming into contact with somebody.

So for example, if you're an institution, let's say at a hospital or a nursing home, or a prison setting where there's an outbreak and you might now be at risk, that is the setting in which this could be indicated to be used as a preventative measure to keep the people who have not yet been infected from being infected.

Do you think we'll start seeing an expansion of monoclonal antibodies, perhaps for those persons who are immunocompromised?

GEORGE D. YANCOPOULOS: We believe that the immunocompromised are a very important population that could really benefit from receiving our antibody cocktail on a monthly basis to keep them protected, to substitute for the fact that they don't generate antibodies in response to vaccines. So we think that's an important potential future authorization, which we are discussing with the FDA.

Once again, the whole point of the vaccine is to generate the body's own antibodies. If the body can't respond to the vaccine by generating its own antibodies, we believe those are perfect candidates to get our own monoclonal antibodies cocktail as a substitute for what you want to get from the vaccine.

Now here you have some compelling data yet like everything else, things don't go as planned. In terms of the rollout, people thought it was just for celebrities. It was sent to hospitals and infusion centers that initially were overwhelmed. We told patients not to come to the hospital, so they're coming too late. What have you learned from the hiccups, the bumps along the way? Which happen all the time. But in the setting of the pandemic when we're trying to reach people, does cause some concerns.

I think that what we learned is it's very hard to be trying to fly an airplane while you're still in the midst of building it. For society, this is really the first time that we've dealt with something like this and trying to implement new weapons simultaneously, such as vaccines and also treatments.

I think it's complicated messaging. It was hard to communicate the importance and the value of both vaccine approaches but also having an antibody cocktail that could act as a treatment, but also as a substitute for the vaccine for those people who don't respond well to the vaccine. These are complicated messages.

It's hard enough just to try to get enough people vaccinated, let alone getting treatments to the people who need them, let alone talking about other applications of antibody cocktail such as for prevention. So I think we've just relearn how complicated it is in the midst of an emergency situation to really implement effective weapons against disease. And we all have to try to do better. And we're trying to.

So what do viewers need to know? A lot of times their doctors are not going to recommend it, either because they're not aware of the indications. It's just not top of mind. They don't know of an infusion center or know that it's up to you. So for listeners and viewers watching that are thinking, hey, I could be a candidate, or you know what? Maybe a loved one should be able to get this. What do they need to do? How do they find out more information?

Yeah. As I said, I think messaging has been complicated. And it's hard for government leaders and policy leaders to explain everything all at once. And so there's been a tremendous focus and rightly so on making sure that as many people as possible get vaccinated.

But the message that needs to get out is that if you're already sick, either because you didn't get the vaccine or because you have a breakthrough infection, if you're at high-risk of advancing to serious disease, there is a treatment out there that is highly effective in preventing serious disease, hospitalization, and death. And that everybody should consider doing that and consider looking into it.

And we need to point this out as you say, because we know that cases are way up, and 99% of them are in the unvaccinated. So there is many people that could benefit from this therapeutic option.

And what the authorization says? If you just found out that you were at an encounter where somebody else has now been diagnosed with COVID, you qualify as having had a high-risk encounter. So maybe you shouldn't wait until you get sick. Go to your doctor, especially if you haven't been vaccinated and get the REGEN-COV antibody cocktail. It can keep you from getting sick.

And there's no cost to patients, correct? That's important to point out to individuals.

This is a really important point. The government is providing these doses for free to individuals for both treatment and for prevention.

So how has the COVID pandemic changed the way that you develop new molecules, the way you think about research, even how you conduct research?

Well, it is definitely true that for most of us at Regeneron, it was just adding another full-time job on top of our already full-time jobs. We did not stop our efforts to cure cancer, to cure blindness, to cure asthma, to cure an assortment of other diseases, or to explore whole new therapies like gene modification in humans. But people started working around the clock, 24/7, to add on this effort to fight back against COVID-19.

So people really pushed themselves to the limit. And very large numbers of people across the board from those doing the earliest discovery work in the labs led by Christos Kyratsous who led our effort here to those working on manufacturing, and ultimately, in distributing the drug at the back end. So everybody throughout the company has literally pushed themselves to the limit.

We have to understand it requires decades and decades of investment in new capabilities and new technologies to then have the power to respond to any particular disease, or in this case to a pandemic. Nobody turns on a dime. It may appear that way to the outside, that people change what they're doing, and so forth.

Yes, people worked 24/7, added another full-time job to their job. These people are scientists, everybody at the company incredibly devoted, dedicated, commitment to making a difference and really helping out the world here, especially since we were at the epicenter in the early days of the pandemic, and we saw it firsthand so many loved ones affected by this disease.

But the real advances were those that were made over the last few decades that allowed us to respond. And this is something that's so critical for the world to understand. There's nothing more important for us as a species, as a humanity, to be able to have the tools to fight back against existential threats, whether it be pandemics or climate change.

We have to be investing in new innovation. It's all about relentless innovation and our commitment as a society that we have to be making those investments, both in academia. In the case of biotech, we have to be increasing our investments, in the NIH and in academic research. But we also have to be encouraging investment in the industry, in the private sector and biotech for people to make the billions of dollars worth of investments that are required to empower these technologies to the point that when we need them, we have them, and we can utilize them, and we can employ them to fight back.

How has COVID changed your leadership style? It's hard to work from home as you point out when you're trying to do lab at the bench. There's only so many things you can do by simulation. How has COVID changed that style for you in terms of dealing with your employees around the world?

Well, of course, our lab people out of necessity, they are true heroes. I put them up there with first responders. They were coming to the labs every day risking their own health and lives in order to try to make a difference to the world. And many of us, myself, I kept coming in every day trying to help lead the efforts along with other major leaders through these efforts.

I don't believe you can do our kind of science virtually. It just doesn't work. And we've recently allowed for a lot more meetings the old style. And I think we've all recognized that the science that we do that has made us leaders over the last couple of decades, in the biotech industry, bring some of most innovative technologies, approaches, and new medicines to the world, all depended on people-- interacting, brainstorming in an incredibly magical way with each other. And we lost a lot of that ability to do the brainstorm.

We could move the work. We could move the science because we had heroes at the bench is working. We were able to do that. But in terms of new ideas, in terms of brainstorming the next great solution to some problem that we didn't understand before, a lot of that has taken a hit.

And many of our leaders, now that we've started to get a little bit back together and let's hope the Delta virus doesn't turn us backwards, have come on the last few weeks that the magic is back now that we have a chance, not to be on these virtual calls where you can't really do what we evolved to do, which is truly synergize with each other, look at each other, understand what we're thinking without even saying it. Those special kind of interactions that are required for optimal brainstorming and synergyzing, that can only occur face to face in meeting rooms. And I hope we're going to be back, able to do that.

I'm going to ask you some predictions, if I may. Do you think we're going to get to the point where we have eradication, elimination? We have some general baseline, endemic, COVID, like the flu all the time? What's your best bet?

We were worried about exactly the situation that we're seeing now, which is evolving variants sprouting up all over the place, and in some cases, perhaps, defeating some of our initial approaches. So that's what we're preparing for. I think that the virus has already proven that it's not going to be easy to eradicate. It's not going to be easy to create herd immunity. There's going to be variants that pop up that are going to defy us over and over again. And so we're already coming up with second and third generation treatments and preventions ourselves.

So we are planning to be prepared for whatever comes at us. And I can only hope that everybody else is doing the same. And I'm sure they are. I know the vaccine makers are trying to make second and third generation vaccines and so forth. So unfortunately right now, this seems like this is going to be a fight that's going to take some of our best and brightest quite a while to get it totally under control.

Are we better prepared for the next pandemic?

Let's hope we can better deal with this pandemic before we have to deal with the next pandemic.

Well, thank you George for taking the time again today.

GEORGE D. YANCOPOULOS: All right. Thank you, John.

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