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Close to the Edge Episode 2: Regeneron’s George Yancopoulos and Aris Baras Discuss Company, COVID-19
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Close to the Edge Episode 2: Regeneron’s George Yancopoulos and Aris Baras Discuss Company, COVID-19
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Segment:0 .
KEVIN DAVIES: Hello, and welcome to Close to the Edge, a new series from GEN Edge where we invite leading executives and scientists from groundbreaking biotech and pharma companies to discuss their science, their technology, and their business. I'm Kevin Davies, hi. And I'm joined by my colleague Alex Philippidis, the Senior Business Editor with Genetic Engineering and Biotechnology News, or GEN, the publication that has been covering the biotech industry for nearly 40 years.
KEVIN DAVIES: Hi, Alex. How are you?
ALEX PHILIPPIDIS: Hi, Kevin, good to be here.
KEVIN DAVIES: Good. Today on Close to the Edge, we're delighted to be joined by two central figures at Regeneron Pharmaceuticals, the Tarrytown, New York-based drug developer. From its founding in 1988 by Len Schleifer, who remains the company's CEO, Regeneron has grown into one of the world's largest biotech companies, with a market cap of more than $50 billion, and more than 9,000 employees worldwide. The company has also emerged as a leader in the field of genomic medicine, the application of sequence data for drug development and clinical trials.
KEVIN DAVIES: More headlines last year when it rolled out one of the first effective COVID-19 therapeutics, administered to many patients, including then President Trump. So joining us today are George Yancopoulos, Regeneron's Chief Scientific Officer and President of Regeneron Laboratories. George joined Regeneron in 1989 as a founding scientist, and is one of the few members of the National Academy of Sciences who come from industry rather than academia.
KEVIN DAVIES: And we're also pleased to welcome Aris Baras, an M.D. who heads the Regeneron Genetics Center, which applies genomics approaches into drug discovery and development with the goal of speeding up research and improving patient care. Gentlemen, thank you so much for coming on Close to the Edge.
GEORGE YANCOPOULOS: Great to be with you guys. Thank you for having us.
KEVIN DAVIES: Alex?
ALEX PHILIPPIDIS: Hi, thanks, Kevin. First, George and Aris, let's ask how you both came to work for Regeneron. George, I know you joined Len Schleifer about a year after the inception of the company. How did you meet, and what drew you to work with each other?
GEORGE YANCOPOULOS: Well, when Len started the company, it was a virtual company, though there was no internet at the time. But it was on paper. And basically, the founding idea was, at the time, Regeneron stood for regenerating neurons. And the notion was to marry what was then the new field of gene cloning with the classical field of neurobiology to try to clone new factors that might aid in helping neurons grow and be healthy.
GEORGE YANCOPOULOS: That was the whole founding premise. So Len, in order to start the company, he really needed a cloner. And so basically, that's where I came in. So he was asking around at the time, not only who was-- it was a very early field as you might remember in the 80s, gene cloning. Not only he needed somebody-- he started out-- the way I sort of say it, at the time, the most noteworthy gene cloner on the planet was David Baltimore.
GEORGE YANCOPOULOS: And so that was Len's first idea-- let me bring on board David Baltimore, the world's premiere gene cloner. Couldn't even get a phone call with David Baltimore. And then, he went down the totem pole of people who are into gene cloning, until he eventually got somebody who answered the phone. That was me. But actually, I really immediately sort of, I think, gelled with Len.
GEORGE YANCOPOULOS: I really sort of appreciated his approach. I thought that he was unlike most business guys who were starting companies who I had met at the time. He was a physician/scientist like me. And he was really interested in trying to do things what I thought was the right way fundamentally by focusing on the science and the research. And so together, then, we took on the challenge of going from becoming a virtual company to a real company, and to starting laboratories, and opening the laboratories, and doing our first experiments, and so forth.
GEORGE YANCOPOULOS: And so that's sort of how it all happened. I mean, I was in academia. I was intrigued by biotech, but I was pretty, at the time, still living the academic life. I got pretty much the equivalent of a cold call from Len. I became intrigued. And then I joined them in starting up Regeneron.
ALEX PHILIPPIDIS: Great! Aris, how did you come to the company?
ARIS BARAS: So similar in some ways, but different in many others. So my version of the story starts in the early 2000s. I had met Roy Vagelos as part of some leadership work and capstone courses that I was doing at Duke University. And he's a legend, of course, both in our industry and as a Greek American. And as I got to know him after that experience, we kept in touch. I entered a different part of my life, which was finishing up my clinical training and research in academia, and figuring out what I'm really going to do in life.
ARIS BARAS: And so he connected me with George. And I spent perhaps a summer or two as I was finishing up some of my research in graduate school at Regeneron, and then made the full time move up in about 2010/2011 to be with Regeneron. It was a very different company back then, I have to say, so less than 1,000 people. And now, we're probably closer to 10,000. You know, I don't know what we are today, maybe $50 billion market cap.
ARIS BARAS: And back then, we might have been a billion or two, had an approved product. And I remember leaving a place like Duke, where a lot of my peers and friends were going off to whether it was McKinsey, or Goldman Sachs, or they were going to household names in venture capital or in industry. And I remember people saying, Regeneron? What's Regeneron?
ARIS BARAS: Why are you going to Regeneron? And it was evident to anyone who knew and would spend just a little bit of time there how amazing the leadership-- Len, George, Roy and hundreds of other people there-- how amazing the science was, and that the potential was all there. And so the last 10 years have been an unbelievable experience and ride.
ARIS BARAS: So I think I picked that one right. Because those same people have been calling me, asking me for jobs at Regeneron now. [CHUCKLES]
ALEX PHILIPPIDIS: Did you ever have any second thoughts in those early years?
ARIS BARAS: No, no.
ALEX PHILIPPIDIS: Now, George--
GEORGE YANCOPOULOS: Let me just add-- I'll tell you, at least from my perspective, about Aris, both his foundation story and also a follow on story. So I'll never forget the day I get a phone call from Roy Vagelos, who's technically, you know, my boss as the Chairman of the company. And he says to me, George, you know, I've been talking to this guy. I really think this guy could make a difference at Regeneron. And so he did say, you know, I may be getting older.
GEORGE YANCOPOULOS: So maybe I'm losing my ability to judge these things. But I really think you've got to call this guy and you got to figure out, is this guy going to really be a difference maker at Regeneron. And you know, Roy gets to interact literally with thousands of people at the highest levels of academia and so forth. So I'm thinking that he's either talking to some industry leader from his various connections, or he's talking about some academic full professor hotshot and all of this.
GEORGE YANCOPOULOS: So I say, OK, Roy, who is this individual? So he goes, well, he's still in medical school. And he goes, and I want you to call him right away, and I want you to figure out, do you think this guy is really special? He could be a real difference maker, a real leader. So I really have to say, I was sort of taken aback. But then I called up Aris. And I became very rapidly convinced that Roy had not lost his edge.
GEORGE YANCOPOULOS: He really had the ability to really recognize talent. And obviously that-- and rapidly, rapidly Aris started making a difference, even if before he came in full-time. Even as an intern-- he did an internship first before he joined us full-time. And it was very clear that he was just different than your average scientist. So then the next thing was, flash forward a few years later.
GEORGE YANCOPOULOS: And we had gotten this idea to get heavily involved into genetics. And our idea actually was to buy the company deCODE, which ultimately got bought by Amgen. But we were sort of in there before Amgen and so forth. But then, to make a long story short, when we end up losing the opportunity for deCODE, our board got very serious. And they said, oh, wow, we may have really missed this opportunity and so forth.
GEORGE YANCOPOULOS: So I said, George, we want you to go out. We want you to recruit-- and there's no limit-- recruit the top geneticist in the world to be involved in starting and founding our Regeneron Genetics Center. And I used-- because Aris was a really, clearly incredible mind who could immediately learn about new fields, and get involved, and so forth.
GEORGE YANCOPOULOS: So I was using him sort of as-- I don't remember what your exact position was, but it was sort of an advisor/consultant on how we were going to start this genetics effort-- not only how we were going to start it, but recruiting the top person in the country. And so we did recruit and talk a lot with some of the world's top geneticists to bring them in. And I'll just never forget that after every one of those meetings with the world's top geneticists, afterwards we had a little sort of post-op discussion with Aris.
GEORGE YANCOPOULOS: And I just kept thinking to myself, huh, I'm actually more impressed with the post-op conversation I'm having with Aris than I had with each one of these world's top geneticists. So I got this crazy idea. I said, why don't we just bet the farm-- or bet the pharma-- on this guy Aris Baras. So I bring it to actually Len, and the board, and everybody.
GEORGE YANCOPOULOS: And I have to say, every single one of them except for one thought I was crazy to be handing over this incredible responsibility and all this to, at the time-- I don't know how old you were, Aris-- but relatively young guy, relatively lack of experience as compared to the world's top geneticists, except for Roy Vagelos. And so he said, you know, I think we should bet on Aris.
GEORGE YANCOPOULOS: And the rest, literally, as they say, is history. Aris, and together with an incredible team of folks that he's recruited over the years, have made us, I think, unquestioned leaders. Now, I mean, we still have enormous respect for the deCODE people, and Kari Stefansson, and so forth. But I think that we are the other comparable leaders in this whole field of human genetics and sequencing, where we've now-- Aris can give you the numbers, but we've probably sequenced more humans than any other organization on the planet.
GEORGE YANCOPOULOS: And it's due to that man-- at least on my Zoom call at the bottom of my screen-- Aris Baras. So never regret it, listening to Roy the first time, you know, when he called me up and told me I needed to talk to this guy. He could be a real difference maker even though he was just a medical student at the time. And then two, never regretted Roy having the confidence, saying, yeah, It's not that crazy.
GEORGE YANCOPOULOS: Go with this guy.
ALEX PHILIPPIDIS: That's quite an endorsement. [CHUCKLES] for Aris. Aris, if you could just sum up a little bit what the Regeneron Genetics Center is, how its work complements and differs from the rest of Regeneron.
ARIS BARAS: Absolutely, thank you, Alex. So in many ways, we are just a fully integrated part of the discovery engine, the part of the engine that really develops therapeutics at Regeneron. And so this whole idea, as you heard about from George, about following genetics is not a new one to Regeneron by any means, right? I mean, Regeneron has always been a genetics and genomics company.
ARIS BARAS: The real realization was that that was the time, and now is the time to do this. So if you look at our first therapeutics, these followed human genetics discoveries, whether it was Arkhalis for a rare autoimmune, auto-inflammatory disorder, looking at things like Praluent, PCSK9, poster child for genetics to therapeutics, the problem was, while we were experts at these things, these things were happening in the community-- the scientific community-- at a low throughput endeavor.
ARIS BARAS: And what we ventured to do was basically crank this thing up, do it at kind of mega scale, and have those types of stories every year, or as is happening to us now, actually, literally every month one of these game changing new discoveries is happening. So we have now sequenced about a million and a half people. We've collaborated with over 100 groups around the world to do that-- very diverse in terms of the people we sequence, the participants in these studies, the different diseases being studied.
ARIS BARAS: From cardiometabolic, to neurodegenerative, to cancer, we're going after all the big ones, everything that is causing a lot of mortality and morbidity. And when we don't know where the targets are and how to develop the best therapeutics, we're going big. We're sequencing hundreds of thousands of people in each of these areas. And simply put, we're looking to identify the genes that cause disease.
ARIS BARAS: And then we can go ahead and try to develop therapeutics to change the biology there and correct those mutations. Or we're also looking for an endeavor that's been a little bit newer in the last decade or so, and that's the flip side of the coin. And we're looking for protective mutations. So going back to that PCSK9 example, giving us that inspiration, and we've now seen a dozen or more of these, not just in cardiometabolic diseases.
ARIS BARAS: But we've seen them in neurogenerative diseases. We've seen them now in obesity. We have a big story coming out on obesity. We've even seen them in cancer. We have found mutations-- variants out there-- that are protective, dramatically reduce your risk for cancer. And that gives us an immediate hypothesis, an immediate path to develop therapeutics that mimic those genetic effects.
ARIS BARAS: And if you've also followed the story carefully of our R&D approach, and our strategies and engine over the last few years, genetics has now really driven us to a place where we're calling genetics medicines. So all the innovations of 10 years ago or even more have led to these amazing antibody therapeutics, including the COVID cocktails that we talk about. But more recently, we've now been going all in, so as George talked about, investing big on big ideas.
ARIS BARAS: We've also invested very big in these genetics medicines technologies, namely RNA interference, CRISPR gene editing types of strategies, and gene therapies. And so we're seeing an increasing amount of our pipeline in these types of therapeutic platforms. And a lot of that, again, was coming back to the fact that we now have this amazing genetics knowledge base to know what genes are causing diseases, and which ones we want to go after, or what genes we can pull the lever on that those can be incredibly protective or beneficial in many disease settings.
ALEX PHILIPPIDIS: We definitely want to get to a little bit more about the RGC later. But you did say something, Aris, that sparked a thought. You mentioned the COVID-19 cocktail. And that has drawn a lot of attention all around the world to Regeneron. George, how has the pandemic and the turmoil of this past year impacted Regeneron? And your COVID cocktail, definitely one of the better news stories that came out of that, was injected into President Trump earlier in October.
ALEX PHILIPPIDIS: And how did both come about?
GEORGE YANCOPOULOS: OK, well, as Aris has been telling you, the history of Regeneron really is a combination of technology and biology, and also the ability to create turnkey technologies that allow us to apply similar approaches over and over again to different problems. And so we had invested-- as many people know over the course of the last few decades-- enormously in developing what we feel are the world's most powerful antibody generation technologies.
GEORGE YANCOPOULOS: And as Aris already outlined, the early days of Regeneron, we were applying traditional, more mouse genetics than human genetics to identify and validate genetics-based targets, and then using a turnkey antibody machine that we had generated to generate therapeutic solutions for these genetics targets. And by continuing to innovate, over many years, the antibody technologies, we just made them more powerful, and quicker, and more rapid to the clinic.
GEORGE YANCOPOULOS: And so we were perfectly poised when the COVID epidemic hit to use these technologies that we had developed, these antibody technologies that we had developed over decades, to very rapidly apply them to the COVID challenge. More recently, before that, and the person who led that program, Christos Kyratsous, he had applied the same antibody technologies that we used to come up with DUPIXENT, and Praluent, and many other of our important new medicines.
GEORGE YANCOPOULOS: He was tasked with figuring out a way to rapidly adapt those technologies to go up against infectious disease targets. And his first success was with Ebola. And as with COVID-19, we came up with the first approved antibody cocktail treatment-- first treatment of any kind approved for Ebola, which was really an incredible advance, and really could make a huge difference in terms of saving lives, as demonstrated by a study that was actually carried out, remarkably enough, in the Congo.
GEORGE YANCOPOULOS: So we had developed the technologies over decades. We had, and particularly Christos had, adapted these technologies to be rapidly deployed in the setting of infectious disease, most notably for Ebola. And then when COVID hit, as I said, we were already in that perfect position. It's not like we had to invent a new technology from scratch. And that's what people have to understand.
GEORGE YANCOPOULOS: This is why investment and innovation across the industry is so important. This is why the industry has to constantly be developing and investing in new forms of innovations. Because not only did our effective treatment come from previous decades of innovation for things that were not designed to fight COVID, they were designed to come up with drugs for other cases. Similarly, for example, the mRNA vaccines that have obviously already started to make such a difference, those depended on innovations that were also more than 10 or 15 years in the making, also intended for completely different purposes, but could be cross applied, now, to the new COVID need.
GEORGE YANCOPOULOS: So that's why it's so important for our industry to be constantly innovating, constantly investing in that, so that when a new challenge comes on board, we have new tools that we can, for the first time, apply for that. And that what was done effectively for the vaccines, as I said, with years of innovation and investment in mRNA technology that was not designed for this purpose, and similarly our antibody technologies.
GEORGE YANCOPOULOS: We invested so much to do that. And then we were able to, very rapidly, within five months of taking on the project, being ready to go into early clinical trials in patients, which have now yielded, in the early forms in the phase I and phase II trials, very positive data. But we've recently had the phase III data come in. So for example, we've shown that treatment of infected patients decreases the risk of hospitalizations or dying by over 70%.
GEORGE YANCOPOULOS: That's really, obviously, hugely impactful. I do think that it's a challenge to be treating. We should-- literally, in this country, there's still 50,000 people getting infected every day. There's still 1,000 people dying each day. We could dramatically be impacting those numbers. We could be, hopefully, keeping 70% of those people from going to hospitals or dying. And we have to do a better job as a society and as a community to figure out how to actually do that.
GEORGE YANCOPOULOS: But we now have a drug that can keep people out of hospitals and from dying. That's really impactful, and that's really important. We've also shown that the same antibody cocktail is very effective at preventing infection. So there are-- as you may know, there's going to be millions of Americans who don't respond to the vaccine, whether they're immunosuppressed because they have organ transplants, or because they have certain cancers, or they suffered from lymphomas or leukemias, or they're on certain drugs, for example, that are routinely used to treat people who have multiple sclerosis, or rheumatoid arthritis, or other diseases.
GEORGE YANCOPOULOS: Those people, the data showing is large percentages of them-- up to 75%, 85%, 90%, depending on the study-- do not respond to vaccines. We've been able to show that our cocktail essentially acts as a passive vaccine. It doesn't require your body to respond to the vaccine to make antibodies. Because we're literally giving you the antibodies that would normally be made in response to a vaccine.
GEORGE YANCOPOULOS: We're giving them to you in the injection, and very effectively can substitute and prevent infection, as we've shown in phase III trials now. So the COVID antibody treatment was really a result of decades' worth of investment, with years' worth of adapting it for infectious disease, and then a very concerted effort to make it all work for COVID-19.
GEORGE YANCOPOULOS: And the phase III trials now really show that it's an effective treatment. But also, for those people who won't be able to respond to vaccines, a very effective prophylactic approach. And so we think, unfortunately, this virus is going to be with us for a while. And this is going to be a very useful weapon to be trying to fight back.
GEORGE YANCOPOULOS: I should point out that the current antibody cocktail was designed prospectively to be able to fight against the predicted variants. So it's still effective against all of the major emerging variants of concern that we're seeing. Plus, we have the ability to rapidly adapt our cocktail in case there were to emerge a new variant that would be resistant to the cocktail which we haven't seen yet.
KEVIN DAVIES: That's great. George, I wanted to--
GEORGE YANCOPOULOS: If I could offer just a quick footnote, Kevin, on this, marrying our topics today about the amazing drug development going on at Regeneron, and the amazing power of genomics in that process, so one of our scientific heroes at Regeneron, Neil Stahl, Executive Vice President of R&D, always says, there's never a failure. We're learning from what we're doing. And it must have been seven, eight years ago, we had one of our first antiviral programs for respiratory syncytial virus, RSV.
GEORGE YANCOPOULOS: And we had a phase III program with a monoclonal antibody that was a smashing success in one trial against the RSV A strain, and then a bomb in the RSV B strain. It didn't work at all. And then Christos, who George just alluded to beforehand, connected with our sequencing guys, and just had to understand what was going on, ended up sequencing all of the viral isolates, and figured out that there was these mutations in all of the RSV B strain, the one that failed, that was right where the antibody binds.
GEORGE YANCOPOULOS: So that was a major learning point, and really helps you understand how Regeneron learned, and how we made multiple antibiotic cocktails ever since, and what you're seeing history replay itself right now. The monoclonals out there have basically just selected for new variants that have escaped those. And as George said, we'd learned that lesson beforehand, and so prospectively created these cocktails.
GEORGE YANCOPOULOS: And so far, knock on wood, they've held up. But of course, there's many backups ready if we need them.
KEVIN DAVIES: That's great. Thank you, Aris, for that. George, your most famous patient, I think Alex already mentioned, was then President Trump about six or eight months ago. How did that come about? And did that give you any anxious moments?
GEORGE YANCOPOULOS: Well, it was right after we had released our phase II data that showed how remarkably effective-- it wasn't the definitive data, but it was the phase II data. It ended up being the data that led to the initial authorization. As I said, we now have phase III data that are confirmatory at a larger scale. And remarkably enough, literally in the same week that we released that data, we were contacted by the White House.
GEORGE YANCOPOULOS: And they had a very important case of a patient who was very early on. They had just diagnosed. And they asked us a lot of questions. They obviously had pored through the data that was available. We had put all the data out publicly. And they wanted to know whether we thought that it would make a difference. Of course, they came to their own decision.
GEORGE YANCOPOULOS: And so they applied-- the White House physician actually applied through the Compassionate Use program to allow for compassionate use, for the President, of our antibody cocktail. There had been actually quite a few other individuals-- less noteworthy, obviously-- who had already applied through that process. And so the process was in place. As you know, it has to be approved both by an internal committee, but also by the FDA for each individual patient.
GEORGE YANCOPOULOS: And that was done. Of course, we were anxious. But the President seemed to respond like the typical early patients in our study. I think that he was given a lot of potential treatments. But I think the only one that was consistent with the type of response that he had, that is a very rapid lowering of his virus, together with this rapid recovery, was probably our treatment.
GEORGE YANCOPOULOS: So I think that really, the thing that made a difference, and may have kept him from progressing to more serious disease, could very well have been the antibody cocktail that he got from Regeneron.
KEVIN DAVIES: That's great. You've already addressed aspects of this next question. But today, we're recording this interview or holding this interview in May, 2021. We've got more than 30% of the American population now fully vaccinated. So that's good news. But you've talked about, still, the benefits of your therapeutic as a "passive vaccine," which is a phrase I hadn't heard before.
KEVIN DAVIES: But that's an interesting way of putting it. So you still, I take it, see a significant opportunity and benefits for pushing the therapeutic that's still a medical need for this. And in particular, I'm wondering if you see a particular need in India, where the scenes are just absolutely devastating?
GEORGE YANCOPOULOS: Yeah, I'm not sure if it's been announced publicly, but it will be by the time this airs, that India regulatory authorities just recently reviewed our cocktail. And they just recently authorized for use in India. And we know that there have been a lot of discussions, because we provide our treatment to the US government, which decides how to employ it. And the US government is very much considering, and is very likely to be shipping substantial numbers of doses to India right now to make a difference there, to try to help control the outbreak, and prevent people from progressing to more serious disease.
GEORGE YANCOPOULOS: So I think that there is going to be, for the foreseeable future, a lot of potential to be treating patients who are getting infected worldwide, whether it's in the United States-- as I said, it's still a big problem in the United States. We have to do a better job of treating every infected person in the United States. It will also be a way to control these variants. Because if you don't treat them, the variants will amplify and grow, and lead to even worse variants.
GEORGE YANCOPOULOS: So I think that we have to do a much better job as a society to try to figure out how to treat. And we have the capacity now to treat every infected American. But also, worldwide, there's going to be an enormous need. We have a partnership, XUS, us with Roche to provide it outside the US. And I know that they're working hard. Because they see that there is going to be, for the foreseeable future, a great need as there is now in India.
GEORGE YANCOPOULOS: But we don't know where the next major outbreaks may occur. That said, there may also be a very long-term, chronic use setting where a lot of people who don't respond to vaccines-- so remember, the vaccine trials were only done in people who were thought to be able to respond to vaccines. These immunosuppressed individuals were actually excluded from their trials. What we now know, as I said, from a series of trials that are being reported from a variety of places which are now studying immunosuppressed people, the vast majority of immunosuppressed people do not mount measurable responses to vaccines at all.
GEORGE YANCOPOULOS: That means that they are entirely still susceptible. Not only are they susceptible to getting infected, but you would expect that they would have the worst outcomes. Because they don't have their own immune system. We essentially have an immune system in a bottle that we can now give them. And as I said, the numbers are actually quite imposing in terms of, if you put together all of these categories of immunosuppressed people, whether it's people with lymphoma and leukemia, or a history of those, or other cancers, or organ transplants, or people with multiple sclerosis, or other diseases that are treated with immunosuppressive drugs and so forth, there's millions of people in America alone who we are going to probably need to figure out a way to keep from getting infected, short of keeping them quarantined all the time.
GEORGE YANCOPOULOS: And it looks like our treatment has the ability to do so, based on the data that we've seen in phase III, which is that it can essentially protect and prevent infection as well as the best people who respond to vaccines. But now, we can give that sort of protection to the people who won't respond to vaccines. So that is something that we are certainly working on and gearing up to do, to figure out how we can come up with a solution for all of these people.
GEORGE YANCOPOULOS: And we're working both with physicians representing all of these patient populations, as well as the FDA, to figure out how to make this available. As I said, essentially, it's a passive vaccine. These people would probably need to get a shot every month or every couple of months. But it would keep them protected. Many of these people are actually used to getting what they call IVIg, intravenous immunoglobulin, because they're immunosuppressed not only to COVID, but to a bunch of other diseases that cause infections.
GEORGE YANCOPOULOS: And there's some protection afforded by IVIg. Because the average population often has protective antibodies against the most common sorts of pathogens. So these people are used to getting protective immunoglobulin therapies in many cases. In this case, you would imagine you would supplement it with a very powerful anti-COVID therapeutic that would protect them against COVID-19 in particular.
KEVIN DAVIES: Thanks. I know Alex wants to just pick up on one or two of the other highlights in your pipeline. And then we'll bring Aris back in. Alex?
ALEX PHILIPPIDIS: Sure, one thing that really struck me within the pipeline is DUPIXENT. Its indications include atopic dermatitis, rhinosinusitis, asthma, and the emergence of a possibly major new therapeutic area in allergy treatment. Is DUPIXENT Regeneron's answer to Humira, this multi-indication, multi-blockbuster?
GEORGE YANCOPOULOS: You know, it's another area-- in order to make advances, many times you have to be really working at it for years, and years, and years. We've been working on this problem, in terms of allergic disease, for decades now. I've personally been working on it since the early 1980s. And I do think that we have literally hit upon the important pathway, or the sister pathways, that are critical perhaps for most, if not all, allergic disease.
GEORGE YANCOPOULOS: And the clinical data with DUPIXENT are proving that. So basically, right now, we have incredible clinical trial data now with DUPIXENT in a series of allergic disease settings, like you mentioned, whether it be asthma, whether it be atopic dermatitis, whether it be rhinosinusitis with nasal polyposis. Most recently, we reported our very positive phase III in eosinophilic esophagitis. Plus, we've shown that it can be important in fundamental basic allergies, such as in peanut allergy.
GEORGE YANCOPOULOS: So we believe that the targets of DUPIXENT, that is the interleukin 4 and interleukin 13 pathway, they may be-- based on the science that we and others have done over decades, they may be the critical drivers of fundamental allergic responses. And because so many diseases have an allergic basis, all of the ones that we mentioned and more that we're currently studying, it may be able to bring relief, and help, and maybe even be disease modifying for millions, and millions, and millions of patients.
GEORGE YANCOPOULOS: And it's an incredible story, I think. It's still a long way from being finished in terms of all the good that it can possibly do. But most importantly-- and this also goes with the biology, and also the genetics. A lot of the validation of these pathways came based on old, but also a lot of more recent work that's been done by Aris and the whole Regeneron Genetics Center-- is not only the importance of this pathway for the allergic disease, but also that it's not important for fighting most other forms of basic infections.
GEORGE YANCOPOULOS: So the safety profile of DUPIXENT makes it. It distinguishes it from Humira. And it distinguishes from, for example, JAK inhibitors. And it distinguishes it from most of other biologics that are trying to attack immune conditions. Because most of those result in immunosuppression, and then you're going to need something like our COVID cocktail to protect you from COVID-19. Or you're going to need other approaches where you're going to be susceptible to infection.
GEORGE YANCOPOULOS: So we treatment with Humira, treatment with other TNF blockers, all the sorts of these immune modulators, the ones for psoriasis, they all come with a serious immunosuppressive risk, and an increased risk of infection. The remarkable thing is you don't see that with DUPIXENT, because this pathway seems to be very limited, and limited towards allergic responses and not for fighting the most important infections that we have to worry about.
GEORGE YANCOPOULOS: So numerically, actually, infections in DUPIXENT treated patients, versus placebo treated patients-- for the conditions that you mentioned, most notably for atopic dermatitis-- you actually decrease the risk of infections. Because you now keep the immune system from being diverted towards a inefficient, inappropriate allergic response. Instead of diverting the immune system to wasting its time on creating useless allergic responses that are only harmful to you, you now allow the immune system to focus back in what it should be focusing on, which is on fighting infection.
GEORGE YANCOPOULOS: So you cure the allergic disease while actually benefiting your ability to actually fight infection. So in some ways, it's a better story, I think, than Humira.
ALEX PHILIPPIDIS: Aris, how does RGC play a role in DUPIXENT, for example, in its expansion of indications and in bringing that--
ARIS BARAS: Yeah, just as George touched on, so we now have genetic signatures. We can look at genetic variants in that pathway. And the first set of experiments were wow, they immediately line up with asthma, for example, right? But then you start to see other areas, other immune conditions, allergies that have genetic signal in this IL-4 pathway. So these are things that, as George mentioned, new genetics that can help us extend on what we know about that pathway, or sister molecules, sister pathways as George talked about.
ARIS BARAS: And in our pipeline, the itepekimab, or IL-33 program, and now that's in COPD, for example, right? And we use the exact same approaches, looking at genetics of IL-33, both gain of function that cause disease, loss of function that protect from it. And that really lined up the genetics to therapeutics approach in asthma and COPD. So it's really exactly as George described.
GEORGE YANCOPOULOS: Well, maybe a great story-- maybe this will be a great story to sort of, as a big finish here, is we've been talking about our approaches to come up with therapeutics, whether it be antibody approaches or others. Aris has talked about how we've incorporated genetics medicines through our collaborations with Alnylam or Intellia, such as siRNA or CRISPR approaches to attack genes. But we're constantly-- I mean, we're constantly working together.
GEORGE YANCOPOULOS: The people who are developing the therapeutics, who are doing the clinical trials, are working, for example, with Aris in the Genetics Group to understand the genetics basis of disease even when you have an effective treatment. And Aris and his team have just made, I think, an incredibly exciting and very logical finding in COVID-19, which, as you all know, we've just talked about it.
GEORGE YANCOPOULOS: We have an effective treatment. But they've realized a susceptibility locus that either helps protect you, or depending on your gene variation, or puts you at increased risk for getting COVID-19, which makes a lot of sense. And it only comes from their ability to have their genetics approaches. So maybe you want to touch upon that story, Aris. And that would be a great way to highlight how we do everything all together.
ARIS BARAS: Absolutely, no, and just like your message before, you know, this is one of those things where I think it's a paper that's just being submitted, or will be this info we put on the preprint. So I'm sure by the time we go live, this will be out there. But it's a logical culprit, looking at ACE2, the receptor that COVID requires to enter cells. And it was amazing. So we studied 50,000 people with COVID, and then hundreds of thousands of controls, and looking for what genes, what variants can lead to those who are getting very sick-- hospitalization, severe disease, death-- versus those that are just having a very mild, benign course.
ARIS BARAS: And so it turns out that you have to go big. You have to look at sequencing. You have to look at large numbers. But there are these very rare mutations that actually dramatically decrease the amount of ACE2 that you have on your cells, are those cells that express ACE2. And those people, just having one copy down, have about a 40% reduction in the risk of hospitalizations and severe disease.
ARIS BARAS: So it makes total sense, and really, the types of genetic discoveries we love to stumble upon.
ALEX PHILIPPIDIS: Kevin?
KEVIN DAVIES: Thanks, guys, just a couple of questions before we close. Aris, you've completed, I think you said, 1 1/2 million exomes-- there or thereabouts. How do you-- you've already given us a couple of examples. But how do you, overall, measure the ROI of that significant investment and effort? How is that information translated into the way that you manage clinical trials, stratify patient populations, and sort of pick winners and losers in the company's pipeline?
ARIS BARAS: You nailed it. So there's really only two ways. One is a very pragmatic one, and how are we doing in terms of new targets, in terms of our development programs, all the things you mentioned? And the other one is a little bit more open ended. And how are we doing in terms of advancing our scientific horizons at Regeneron, new areas that we didn't even know about when we started this whole initiative?
ARIS BARAS: So on the first one, it's been a smashing success. Len and George always told us, if we just get one-- just get one more PCSK9 or program like that, it'll be worth it. It'll pay it off, as you said, in terms of the ROI. And here we are today, something like-- depending on how you count-- maybe 12 or 15 new programs we've started, the most advanced ones that are in the clinic and are publicly known, like the Alnylam HSD17B13 program.
ARIS BARAS: But there's a lot behind it, and quite a few approaching the clinic. And as we talked about, in terms of things that are in development, we do a lot to help in terms of evaluating safety, or helping pick new indications, or helping identify biomarkers that enrich for those who are going to respond more favorably to our drug. But on the other hand, there are so many new areas that we explore.
ARIS BARAS: And we're committed to getting to 5 million, to 50 million people sequenced. We started this endeavor to find new targets. Now, we've got a whole new genetics medicine capability at Regeneron and amazing partnerships with some of the best in the world in these platforms. And perhaps, one of the new areas will be, we've realized that this data is incredibly powerful in terms of changing the way providers practice medicine, and the fact that the whole world-- the whole world of medicine at least-- really needs to get to an early detection model.
ARIS BARAS: We have to be able to detect things earlier. We have to be able to look at data, and to know with much more accuracy what risks-- what health risks someone's going to have. And then, how do you intervene in an earlier time point? And we're telling you, this data-- genomic data, and imaging data, and other molecular data-- are the key to do that in the future. And it's rapidly coming.
ARIS BARAS: The one analogy I like to offer, not in my day, but back in George's day when people could remember big supercomputers and we didn't have laptops at our-- everywhere, or--
GEORGE YANCOPOULOS: Days of the giants, Aris.
ARIS BARAS: Exactly, days of the giants whose shoulders we stand on now. But no, I mean, it's-- you cannot look anywhere in your rooms without a dozen example of Michael Electronics in that room, every street corner. And that's what's happening in medicine and genomics. It used to be, 10 years ago, that genomics was that supercomputer that George knew about. But now, we're rapidly get into a place where genomics is going to be ubiquitous in medicine, not in the areas that we've already established in therapeutics and all that, but just in how medicine is practiced.
ARIS BARAS: And so there are some tidbits on how we measure success, and how bright-eyes and how big we think about genomics.
KEVIN DAVIES: For both of you, we'd love to ask what new technologies are going to change either your particular corner of the company, or perhaps more broadly the face of drug discovery and therapeutics over the next 5 to 10 years. Aris, I'll start with you. And then maybe we'll give George the last word.
ARIS BARAS: Absolutely, so I've touched on them, really. I think that these capabilities in terms of RNA interference and CRISPR technologies, we have maybe less than a handful or so of approved therapeutics in the world from those technologies. But they're rapidly coming. And they're allowing us to unlock a lot of target space. So that's going to change the industry for sure. And I also think data-- what we're doing with genetics, what we're doing as a community with imaging, and machine learning, and AI-- that is unbelievable in its potential.
KEVIN DAVIES: George, would you like to follow that?
GEORGE YANCOPOULOS: Yeah, well, it's hard to follow that or add to that. But I do think that it's important to just highlight a couple of points, which is that, as I said, the history of Regeneron is marrying sort of technology with ideas. And the Regeneron Genetics Center is a great example of that. So what did they do? They married technologies.
GEORGE YANCOPOULOS: In most cases, it was a robotic space technology that was allowing them to now sequence at a scale that had never been sequenced before. It's not the sequencing machines that are the limiting thing, it's the process handling, and all of that that is still, in most places, done by human beings by hand. That they were able to actually automate and robotize that allowed them to work at a completely different scale, that then allowed them to create big data at a scale that was never generated before.
GEORGE YANCOPOULOS: And it was not only doing the sequencing, but finding the right populations of people to sequence, each one coming with their electronic records. Once they did that, to me, that is one of the biggest things that's been done in the biotech industry over the last five years. And as Aris says, he's only going to up the game by another order of magnitude or two, which is going to only further increase the information in the big data that we have.
GEORGE YANCOPOULOS: So big data is only as good as the data itself. And most big data that we have is not as amenable to machine learning approaches, and so forth, as is really this data that is well organized in a manner that can really be used in that function. So I think that this is going to end up being revolutionary. And we are trying to prepare for it, as Aris says, in two ways. One way is by turning this information into medicines.
GEORGE YANCOPOULOS: And what we recognize is that a powerful tool to turn them to medicines that we already had in our repertoire were the antibodies. So all of the targets, all of the genes that are working, that deliver products, proteins that are outside of the body we can address with antibodies. But there's a lot of these new genes, and discoveries, and big data that's pointing us to genes that we can't address with antibodies.
GEORGE YANCOPOULOS: And so this led us to make these critical alliances and collaborations with the companies that we thought were the leaders in the types of approaches, the new turnkey technologies after antibodies, that we're going to empower us to take advantage of all of the genetic targets that Aris and his team are discovering. And one of those is our major collaboration with Alnylam. So just like we were the best in the world at providing antibody solutions for our genetic targets, now working with Alnylam, we're going to be the best in the world at delivering siRNA solutions for our genetic targets, or within Intellia, CRISPR solutions, or with certain other collaborations, what we're doing internally, viral gene delivery solutions.
GEORGE YANCOPOULOS: So I think the biggest thing in biotech is creation of really important biotech big data, which Aris is generating-- the ability to turn into drugs based on our existing capabilities, but also these important, critical new alliances. And then the third real big opportunity that's going to come from the big data is what Aris just said, is applying all that information not only for drug discovery and to come up with the next great, important medicines, but to understand how to take advantage of that information so as to empower physicians so that they can actually provide better medicine based on existing solutions.
GEORGE YANCOPOULOS: Right now, no physician can possibly integrate all of the genetics information with all the clinical information and do justice to every single patient. Whereas, we think that by generating this data, and generating a solution that will allow them to do so, we may be empowering physicians with current solutions, let alone the new weapons that we're going to hopefully bring into their armamentarium-- a whole new age of healthcare delivery.
KEVIN DAVIES: Fantastic, if we've got 60 seconds, Alex, number 11, you had a good question, I think.
ALEX PHILIPPIDIS: Sure, what does Regeneron-- you mentioned working with Washington to get the antibody cocktail to India. What does Regeneron want to see or not see from the Biden administration?
GEORGE YANCOPOULOS: Well, I think that the most important thing-- and this is not for Regeneron itself-- is that we have to understand that there's nothing more important than incentivizing relentless innovation. Without that, literally the fate of humanity comes into question. We have true existential threats. They're not going to be solved by figuring out how to parse our savings, and how to control healthcare costs, and optimize that, and so forth.
GEORGE YANCOPOULOS: That's not what's going to save us, OK? To fight the existential threats of things like disease, future pandemics, but not to mention scourges that are going to come down in epidemic proportions like type 2 diabetes and Alzheimer's, we need new innovation to create new solutions for that. And the Administration has to recognize that there's nothing more important than the long-term solutions that can only be provided by new innovation.
GEORGE YANCOPOULOS: That requires much, much more investment. So whatever they're doing, they have to come up with a plan that does not decrease the investment and the incentivization that will bring forth the new discoveries and the new investments in technologies that will prepare us. As I said at the top, and this come full circle, the only reason the vaccine guys could employ mRNA technology to come up with these vaccines was because they had been investing in the technology, not for pandemic purposes, but for other purposes.
GEORGE YANCOPOULOS: The only reason we could come up with our effective therapeutic against COVID-19 is because we had been investing in these capabilities for decades, not to fight COVID-19, but to develop these technologies for other purposes. We have to recognize relentless innovation, incentivizing it. There's nothing more important than doing that. And I can only hope that this administration and future administrations recognize that.
KEVIN DAVIES: Thank you, George, great notes to end on. And that's all the time we have for this episode of Close to the Edge. Our sincere thanks to George Yancopoulos and Aris Baras from Regeneron for a fascinating discussion. I hope the rest of the episodes in this series live up to what we've just heard. For Alex Philippidis, my colleague, producer Jamie Cohen, and the entire GEN Edge team, thanks for joining us.
KEVIN DAVIES: I'm Kevin Davies. See you next time. Bye bye for now.
Segment:0 .
KEVIN DAVIES: Hello, and welcome to Close to the Edge, a new series from GEN Edge where we invite leading executives and scientists from groundbreaking biotech and pharma companies to discuss their science, their technology, and their business. I'm Kevin Davies, hi. And I'm joined by my colleague Alex Philippidis, the Senior Business Editor with Genetic Engineering and Biotechnology News, or GEN, the publication that has been covering the biotech industry for nearly 40 years.
KEVIN DAVIES: Hi, Alex. How are you?
ALEX PHILIPPIDIS: Hi, Kevin, good to be here.
KEVIN DAVIES: Good. Today on Close to the Edge, we're delighted to be joined by two central figures at Regeneron Pharmaceuticals, the Tarrytown, New York-based drug developer. From its founding in 1988 by Len Schleifer, who remains the company's CEO, Regeneron has grown into one of the world's largest biotech companies, with a market cap of more than $50 billion, and more than 9,000 employees worldwide. The company has also emerged as a leader in the field of genomic medicine, the application of sequence data for drug development and clinical trials.
KEVIN DAVIES: More headlines last year when it rolled out one of the first effective COVID-19 therapeutics, administered to many patients, including then President Trump. So joining us today are George Yancopoulos, Regeneron's Chief Scientific Officer and President of Regeneron Laboratories. George joined Regeneron in 1989 as a founding scientist, and is one of the few members of the National Academy of Sciences who come from industry rather than academia.
KEVIN DAVIES: And we're also pleased to welcome Aris Baras, an M.D. who heads the Regeneron Genetics Center, which applies genomics approaches into drug discovery and development with the goal of speeding up research and improving patient care. Gentlemen, thank you so much for coming on Close to the Edge.
GEORGE YANCOPOULOS: Great to be with you guys. Thank you for having us.
KEVIN DAVIES: Alex?
ALEX PHILIPPIDIS: Hi, thanks, Kevin. First, George and Aris, let's ask how you both came to work for Regeneron. George, I know you joined Len Schleifer about a year after the inception of the company. How did you meet, and what drew you to work with each other?
GEORGE YANCOPOULOS: Well, when Len started the company, it was a virtual company, though there was no internet at the time. But it was on paper. And basically, the founding idea was, at the time, Regeneron stood for regenerating neurons. And the notion was to marry what was then the new field of gene cloning with the classical field of neurobiology to try to clone new factors that might aid in helping neurons grow and be healthy.
GEORGE YANCOPOULOS: That was the whole founding premise. So Len, in order to start the company, he really needed a cloner. And so basically, that's where I came in. So he was asking around at the time, not only who was-- it was a very early field as you might remember in the 80s, gene cloning. Not only he needed somebody-- he started out-- the way I sort of say it, at the time, the most noteworthy gene cloner on the planet was David Baltimore.
GEORGE YANCOPOULOS: And so that was Len's first idea-- let me bring on board David Baltimore, the world's premiere gene cloner. Couldn't even get a phone call with David Baltimore. And then, he went down the totem pole of people who are into gene cloning, until he eventually got somebody who answered the phone. That was me. But actually, I really immediately sort of, I think, gelled with Len.
GEORGE YANCOPOULOS: I really sort of appreciated his approach. I thought that he was unlike most business guys who were starting companies who I had met at the time. He was a physician/scientist like me. And he was really interested in trying to do things what I thought was the right way fundamentally by focusing on the science and the research. And so together, then, we took on the challenge of going from becoming a virtual company to a real company, and to starting laboratories, and opening the laboratories, and doing our first experiments, and so forth.
GEORGE YANCOPOULOS: And so that's sort of how it all happened. I mean, I was in academia. I was intrigued by biotech, but I was pretty, at the time, still living the academic life. I got pretty much the equivalent of a cold call from Len. I became intrigued. And then I joined them in starting up Regeneron.
ALEX PHILIPPIDIS: Great! Aris, how did you come to the company?
ARIS BARAS: So similar in some ways, but different in many others. So my version of the story starts in the early 2000s. I had met Roy Vagelos as part of some leadership work and capstone courses that I was doing at Duke University. And he's a legend, of course, both in our industry and as a Greek American. And as I got to know him after that experience, we kept in touch. I entered a different part of my life, which was finishing up my clinical training and research in academia, and figuring out what I'm really going to do in life.
ARIS BARAS: And so he connected me with George. And I spent perhaps a summer or two as I was finishing up some of my research in graduate school at Regeneron, and then made the full time move up in about 2010/2011 to be with Regeneron. It was a very different company back then, I have to say, so less than 1,000 people. And now, we're probably closer to 10,000. You know, I don't know what we are today, maybe $50 billion market cap.
ARIS BARAS: And back then, we might have been a billion or two, had an approved product. And I remember leaving a place like Duke, where a lot of my peers and friends were going off to whether it was McKinsey, or Goldman Sachs, or they were going to household names in venture capital or in industry. And I remember people saying, Regeneron? What's Regeneron?
ARIS BARAS: Why are you going to Regeneron? And it was evident to anyone who knew and would spend just a little bit of time there how amazing the leadership-- Len, George, Roy and hundreds of other people there-- how amazing the science was, and that the potential was all there. And so the last 10 years have been an unbelievable experience and ride.
ARIS BARAS: So I think I picked that one right. Because those same people have been calling me, asking me for jobs at Regeneron now. [CHUCKLES]
ALEX PHILIPPIDIS: Did you ever have any second thoughts in those early years?
ARIS BARAS: No, no.
ALEX PHILIPPIDIS: Now, George--
GEORGE YANCOPOULOS: Let me just add-- I'll tell you, at least from my perspective, about Aris, both his foundation story and also a follow on story. So I'll never forget the day I get a phone call from Roy Vagelos, who's technically, you know, my boss as the Chairman of the company. And he says to me, George, you know, I've been talking to this guy. I really think this guy could make a difference at Regeneron. And so he did say, you know, I may be getting older.
GEORGE YANCOPOULOS: So maybe I'm losing my ability to judge these things. But I really think you've got to call this guy and you got to figure out, is this guy going to really be a difference maker at Regeneron. And you know, Roy gets to interact literally with thousands of people at the highest levels of academia and so forth. So I'm thinking that he's either talking to some industry leader from his various connections, or he's talking about some academic full professor hotshot and all of this.
GEORGE YANCOPOULOS: So I say, OK, Roy, who is this individual? So he goes, well, he's still in medical school. And he goes, and I want you to call him right away, and I want you to figure out, do you think this guy is really special? He could be a real difference maker, a real leader. So I really have to say, I was sort of taken aback. But then I called up Aris. And I became very rapidly convinced that Roy had not lost his edge.
GEORGE YANCOPOULOS: He really had the ability to really recognize talent. And obviously that-- and rapidly, rapidly Aris started making a difference, even if before he came in full-time. Even as an intern-- he did an internship first before he joined us full-time. And it was very clear that he was just different than your average scientist. So then the next thing was, flash forward a few years later.
GEORGE YANCOPOULOS: And we had gotten this idea to get heavily involved into genetics. And our idea actually was to buy the company deCODE, which ultimately got bought by Amgen. But we were sort of in there before Amgen and so forth. But then, to make a long story short, when we end up losing the opportunity for deCODE, our board got very serious. And they said, oh, wow, we may have really missed this opportunity and so forth.
GEORGE YANCOPOULOS: So I said, George, we want you to go out. We want you to recruit-- and there's no limit-- recruit the top geneticist in the world to be involved in starting and founding our Regeneron Genetics Center. And I used-- because Aris was a really, clearly incredible mind who could immediately learn about new fields, and get involved, and so forth.
GEORGE YANCOPOULOS: So I was using him sort of as-- I don't remember what your exact position was, but it was sort of an advisor/consultant on how we were going to start this genetics effort-- not only how we were going to start it, but recruiting the top person in the country. And so we did recruit and talk a lot with some of the world's top geneticists to bring them in. And I'll just never forget that after every one of those meetings with the world's top geneticists, afterwards we had a little sort of post-op discussion with Aris.
GEORGE YANCOPOULOS: And I just kept thinking to myself, huh, I'm actually more impressed with the post-op conversation I'm having with Aris than I had with each one of these world's top geneticists. So I got this crazy idea. I said, why don't we just bet the farm-- or bet the pharma-- on this guy Aris Baras. So I bring it to actually Len, and the board, and everybody.
GEORGE YANCOPOULOS: And I have to say, every single one of them except for one thought I was crazy to be handing over this incredible responsibility and all this to, at the time-- I don't know how old you were, Aris-- but relatively young guy, relatively lack of experience as compared to the world's top geneticists, except for Roy Vagelos. And so he said, you know, I think we should bet on Aris.
GEORGE YANCOPOULOS: And the rest, literally, as they say, is history. Aris, and together with an incredible team of folks that he's recruited over the years, have made us, I think, unquestioned leaders. Now, I mean, we still have enormous respect for the deCODE people, and Kari Stefansson, and so forth. But I think that we are the other comparable leaders in this whole field of human genetics and sequencing, where we've now-- Aris can give you the numbers, but we've probably sequenced more humans than any other organization on the planet.
GEORGE YANCOPOULOS: And it's due to that man-- at least on my Zoom call at the bottom of my screen-- Aris Baras. So never regret it, listening to Roy the first time, you know, when he called me up and told me I needed to talk to this guy. He could be a real difference maker even though he was just a medical student at the time. And then two, never regretted Roy having the confidence, saying, yeah, It's not that crazy.
GEORGE YANCOPOULOS: Go with this guy.
ALEX PHILIPPIDIS: That's quite an endorsement. [CHUCKLES] for Aris. Aris, if you could just sum up a little bit what the Regeneron Genetics Center is, how its work complements and differs from the rest of Regeneron.
ARIS BARAS: Absolutely, thank you, Alex. So in many ways, we are just a fully integrated part of the discovery engine, the part of the engine that really develops therapeutics at Regeneron. And so this whole idea, as you heard about from George, about following genetics is not a new one to Regeneron by any means, right? I mean, Regeneron has always been a genetics and genomics company.
ARIS BARAS: The real realization was that that was the time, and now is the time to do this. So if you look at our first therapeutics, these followed human genetics discoveries, whether it was Arkhalis for a rare autoimmune, auto-inflammatory disorder, looking at things like Praluent, PCSK9, poster child for genetics to therapeutics, the problem was, while we were experts at these things, these things were happening in the community-- the scientific community-- at a low throughput endeavor.
ARIS BARAS: And what we ventured to do was basically crank this thing up, do it at kind of mega scale, and have those types of stories every year, or as is happening to us now, actually, literally every month one of these game changing new discoveries is happening. So we have now sequenced about a million and a half people. We've collaborated with over 100 groups around the world to do that-- very diverse in terms of the people we sequence, the participants in these studies, the different diseases being studied.
ARIS BARAS: From cardiometabolic, to neurodegenerative, to cancer, we're going after all the big ones, everything that is causing a lot of mortality and morbidity. And when we don't know where the targets are and how to develop the best therapeutics, we're going big. We're sequencing hundreds of thousands of people in each of these areas. And simply put, we're looking to identify the genes that cause disease.
ARIS BARAS: And then we can go ahead and try to develop therapeutics to change the biology there and correct those mutations. Or we're also looking for an endeavor that's been a little bit newer in the last decade or so, and that's the flip side of the coin. And we're looking for protective mutations. So going back to that PCSK9 example, giving us that inspiration, and we've now seen a dozen or more of these, not just in cardiometabolic diseases.
ARIS BARAS: But we've seen them in neurogenerative diseases. We've seen them now in obesity. We have a big story coming out on obesity. We've even seen them in cancer. We have found mutations-- variants out there-- that are protective, dramatically reduce your risk for cancer. And that gives us an immediate hypothesis, an immediate path to develop therapeutics that mimic those genetic effects.
ARIS BARAS: And if you've also followed the story carefully of our R&D approach, and our strategies and engine over the last few years, genetics has now really driven us to a place where we're calling genetics medicines. So all the innovations of 10 years ago or even more have led to these amazing antibody therapeutics, including the COVID cocktails that we talk about. But more recently, we've now been going all in, so as George talked about, investing big on big ideas.
ARIS BARAS: We've also invested very big in these genetics medicines technologies, namely RNA interference, CRISPR gene editing types of strategies, and gene therapies. And so we're seeing an increasing amount of our pipeline in these types of therapeutic platforms. And a lot of that, again, was coming back to the fact that we now have this amazing genetics knowledge base to know what genes are causing diseases, and which ones we want to go after, or what genes we can pull the lever on that those can be incredibly protective or beneficial in many disease settings.
ALEX PHILIPPIDIS: We definitely want to get to a little bit more about the RGC later. But you did say something, Aris, that sparked a thought. You mentioned the COVID-19 cocktail. And that has drawn a lot of attention all around the world to Regeneron. George, how has the pandemic and the turmoil of this past year impacted Regeneron? And your COVID cocktail, definitely one of the better news stories that came out of that, was injected into President Trump earlier in October.
ALEX PHILIPPIDIS: And how did both come about?
GEORGE YANCOPOULOS: OK, well, as Aris has been telling you, the history of Regeneron really is a combination of technology and biology, and also the ability to create turnkey technologies that allow us to apply similar approaches over and over again to different problems. And so we had invested-- as many people know over the course of the last few decades-- enormously in developing what we feel are the world's most powerful antibody generation technologies.
GEORGE YANCOPOULOS: And as Aris already outlined, the early days of Regeneron, we were applying traditional, more mouse genetics than human genetics to identify and validate genetics-based targets, and then using a turnkey antibody machine that we had generated to generate therapeutic solutions for these genetics targets. And by continuing to innovate, over many years, the antibody technologies, we just made them more powerful, and quicker, and more rapid to the clinic.
GEORGE YANCOPOULOS: And so we were perfectly poised when the COVID epidemic hit to use these technologies that we had developed, these antibody technologies that we had developed over decades, to very rapidly apply them to the COVID challenge. More recently, before that, and the person who led that program, Christos Kyratsous, he had applied the same antibody technologies that we used to come up with DUPIXENT, and Praluent, and many other of our important new medicines.
GEORGE YANCOPOULOS: He was tasked with figuring out a way to rapidly adapt those technologies to go up against infectious disease targets. And his first success was with Ebola. And as with COVID-19, we came up with the first approved antibody cocktail treatment-- first treatment of any kind approved for Ebola, which was really an incredible advance, and really could make a huge difference in terms of saving lives, as demonstrated by a study that was actually carried out, remarkably enough, in the Congo.
GEORGE YANCOPOULOS: So we had developed the technologies over decades. We had, and particularly Christos had, adapted these technologies to be rapidly deployed in the setting of infectious disease, most notably for Ebola. And then when COVID hit, as I said, we were already in that perfect position. It's not like we had to invent a new technology from scratch. And that's what people have to understand.
GEORGE YANCOPOULOS: This is why investment and innovation across the industry is so important. This is why the industry has to constantly be developing and investing in new forms of innovations. Because not only did our effective treatment come from previous decades of innovation for things that were not designed to fight COVID, they were designed to come up with drugs for other cases. Similarly, for example, the mRNA vaccines that have obviously already started to make such a difference, those depended on innovations that were also more than 10 or 15 years in the making, also intended for completely different purposes, but could be cross applied, now, to the new COVID need.
GEORGE YANCOPOULOS: So that's why it's so important for our industry to be constantly innovating, constantly investing in that, so that when a new challenge comes on board, we have new tools that we can, for the first time, apply for that. And that what was done effectively for the vaccines, as I said, with years of innovation and investment in mRNA technology that was not designed for this purpose, and similarly our antibody technologies.
GEORGE YANCOPOULOS: We invested so much to do that. And then we were able to, very rapidly, within five months of taking on the project, being ready to go into early clinical trials in patients, which have now yielded, in the early forms in the phase I and phase II trials, very positive data. But we've recently had the phase III data come in. So for example, we've shown that treatment of infected patients decreases the risk of hospitalizations or dying by over 70%.
GEORGE YANCOPOULOS: That's really, obviously, hugely impactful. I do think that it's a challenge to be treating. We should-- literally, in this country, there's still 50,000 people getting infected every day. There's still 1,000 people dying each day. We could dramatically be impacting those numbers. We could be, hopefully, keeping 70% of those people from going to hospitals or dying. And we have to do a better job as a society and as a community to figure out how to actually do that.
GEORGE YANCOPOULOS: But we now have a drug that can keep people out of hospitals and from dying. That's really impactful, and that's really important. We've also shown that the same antibody cocktail is very effective at preventing infection. So there are-- as you may know, there's going to be millions of Americans who don't respond to the vaccine, whether they're immunosuppressed because they have organ transplants, or because they have certain cancers, or they suffered from lymphomas or leukemias, or they're on certain drugs, for example, that are routinely used to treat people who have multiple sclerosis, or rheumatoid arthritis, or other diseases.
GEORGE YANCOPOULOS: Those people, the data showing is large percentages of them-- up to 75%, 85%, 90%, depending on the study-- do not respond to vaccines. We've been able to show that our cocktail essentially acts as a passive vaccine. It doesn't require your body to respond to the vaccine to make antibodies. Because we're literally giving you the antibodies that would normally be made in response to a vaccine.
GEORGE YANCOPOULOS: We're giving them to you in the injection, and very effectively can substitute and prevent infection, as we've shown in phase III trials now. So the COVID antibody treatment was really a result of decades' worth of investment, with years' worth of adapting it for infectious disease, and then a very concerted effort to make it all work for COVID-19.
GEORGE YANCOPOULOS: And the phase III trials now really show that it's an effective treatment. But also, for those people who won't be able to respond to vaccines, a very effective prophylactic approach. And so we think, unfortunately, this virus is going to be with us for a while. And this is going to be a very useful weapon to be trying to fight back.
GEORGE YANCOPOULOS: I should point out that the current antibody cocktail was designed prospectively to be able to fight against the predicted variants. So it's still effective against all of the major emerging variants of concern that we're seeing. Plus, we have the ability to rapidly adapt our cocktail in case there were to emerge a new variant that would be resistant to the cocktail which we haven't seen yet.
KEVIN DAVIES: That's great. George, I wanted to--
GEORGE YANCOPOULOS: If I could offer just a quick footnote, Kevin, on this, marrying our topics today about the amazing drug development going on at Regeneron, and the amazing power of genomics in that process, so one of our scientific heroes at Regeneron, Neil Stahl, Executive Vice President of R&D, always says, there's never a failure. We're learning from what we're doing. And it must have been seven, eight years ago, we had one of our first antiviral programs for respiratory syncytial virus, RSV.
GEORGE YANCOPOULOS: And we had a phase III program with a monoclonal antibody that was a smashing success in one trial against the RSV A strain, and then a bomb in the RSV B strain. It didn't work at all. And then Christos, who George just alluded to beforehand, connected with our sequencing guys, and just had to understand what was going on, ended up sequencing all of the viral isolates, and figured out that there was these mutations in all of the RSV B strain, the one that failed, that was right where the antibody binds.
GEORGE YANCOPOULOS: So that was a major learning point, and really helps you understand how Regeneron learned, and how we made multiple antibiotic cocktails ever since, and what you're seeing history replay itself right now. The monoclonals out there have basically just selected for new variants that have escaped those. And as George said, we'd learned that lesson beforehand, and so prospectively created these cocktails.
GEORGE YANCOPOULOS: And so far, knock on wood, they've held up. But of course, there's many backups ready if we need them.
KEVIN DAVIES: That's great. Thank you, Aris, for that. George, your most famous patient, I think Alex already mentioned, was then President Trump about six or eight months ago. How did that come about? And did that give you any anxious moments?
GEORGE YANCOPOULOS: Well, it was right after we had released our phase II data that showed how remarkably effective-- it wasn't the definitive data, but it was the phase II data. It ended up being the data that led to the initial authorization. As I said, we now have phase III data that are confirmatory at a larger scale. And remarkably enough, literally in the same week that we released that data, we were contacted by the White House.
GEORGE YANCOPOULOS: And they had a very important case of a patient who was very early on. They had just diagnosed. And they asked us a lot of questions. They obviously had pored through the data that was available. We had put all the data out publicly. And they wanted to know whether we thought that it would make a difference. Of course, they came to their own decision.
GEORGE YANCOPOULOS: And so they applied-- the White House physician actually applied through the Compassionate Use program to allow for compassionate use, for the President, of our antibody cocktail. There had been actually quite a few other individuals-- less noteworthy, obviously-- who had already applied through that process. And so the process was in place. As you know, it has to be approved both by an internal committee, but also by the FDA for each individual patient.
GEORGE YANCOPOULOS: And that was done. Of course, we were anxious. But the President seemed to respond like the typical early patients in our study. I think that he was given a lot of potential treatments. But I think the only one that was consistent with the type of response that he had, that is a very rapid lowering of his virus, together with this rapid recovery, was probably our treatment.
GEORGE YANCOPOULOS: So I think that really, the thing that made a difference, and may have kept him from progressing to more serious disease, could very well have been the antibody cocktail that he got from Regeneron.
KEVIN DAVIES: That's great. You've already addressed aspects of this next question. But today, we're recording this interview or holding this interview in May, 2021. We've got more than 30% of the American population now fully vaccinated. So that's good news. But you've talked about, still, the benefits of your therapeutic as a "passive vaccine," which is a phrase I hadn't heard before.
KEVIN DAVIES: But that's an interesting way of putting it. So you still, I take it, see a significant opportunity and benefits for pushing the therapeutic that's still a medical need for this. And in particular, I'm wondering if you see a particular need in India, where the scenes are just absolutely devastating?
GEORGE YANCOPOULOS: Yeah, I'm not sure if it's been announced publicly, but it will be by the time this airs, that India regulatory authorities just recently reviewed our cocktail. And they just recently authorized for use in India. And we know that there have been a lot of discussions, because we provide our treatment to the US government, which decides how to employ it. And the US government is very much considering, and is very likely to be shipping substantial numbers of doses to India right now to make a difference there, to try to help control the outbreak, and prevent people from progressing to more serious disease.
GEORGE YANCOPOULOS: So I think that there is going to be, for the foreseeable future, a lot of potential to be treating patients who are getting infected worldwide, whether it's in the United States-- as I said, it's still a big problem in the United States. We have to do a better job of treating every infected person in the United States. It will also be a way to control these variants. Because if you don't treat them, the variants will amplify and grow, and lead to even worse variants.
GEORGE YANCOPOULOS: So I think that we have to do a much better job as a society to try to figure out how to treat. And we have the capacity now to treat every infected American. But also, worldwide, there's going to be an enormous need. We have a partnership, XUS, us with Roche to provide it outside the US. And I know that they're working hard. Because they see that there is going to be, for the foreseeable future, a great need as there is now in India.
GEORGE YANCOPOULOS: But we don't know where the next major outbreaks may occur. That said, there may also be a very long-term, chronic use setting where a lot of people who don't respond to vaccines-- so remember, the vaccine trials were only done in people who were thought to be able to respond to vaccines. These immunosuppressed individuals were actually excluded from their trials. What we now know, as I said, from a series of trials that are being reported from a variety of places which are now studying immunosuppressed people, the vast majority of immunosuppressed people do not mount measurable responses to vaccines at all.
GEORGE YANCOPOULOS: That means that they are entirely still susceptible. Not only are they susceptible to getting infected, but you would expect that they would have the worst outcomes. Because they don't have their own immune system. We essentially have an immune system in a bottle that we can now give them. And as I said, the numbers are actually quite imposing in terms of, if you put together all of these categories of immunosuppressed people, whether it's people with lymphoma and leukemia, or a history of those, or other cancers, or organ transplants, or people with multiple sclerosis, or other diseases that are treated with immunosuppressive drugs and so forth, there's millions of people in America alone who we are going to probably need to figure out a way to keep from getting infected, short of keeping them quarantined all the time.
GEORGE YANCOPOULOS: And it looks like our treatment has the ability to do so, based on the data that we've seen in phase III, which is that it can essentially protect and prevent infection as well as the best people who respond to vaccines. But now, we can give that sort of protection to the people who won't respond to vaccines. So that is something that we are certainly working on and gearing up to do, to figure out how we can come up with a solution for all of these people.
GEORGE YANCOPOULOS: And we're working both with physicians representing all of these patient populations, as well as the FDA, to figure out how to make this available. As I said, essentially, it's a passive vaccine. These people would probably need to get a shot every month or every couple of months. But it would keep them protected. Many of these people are actually used to getting what they call IVIg, intravenous immunoglobulin, because they're immunosuppressed not only to COVID, but to a bunch of other diseases that cause infections.
GEORGE YANCOPOULOS: And there's some protection afforded by IVIg. Because the average population often has protective antibodies against the most common sorts of pathogens. So these people are used to getting protective immunoglobulin therapies in many cases. In this case, you would imagine you would supplement it with a very powerful anti-COVID therapeutic that would protect them against COVID-19 in particular.
KEVIN DAVIES: Thanks. I know Alex wants to just pick up on one or two of the other highlights in your pipeline. And then we'll bring Aris back in. Alex?
ALEX PHILIPPIDIS: Sure, one thing that really struck me within the pipeline is DUPIXENT. Its indications include atopic dermatitis, rhinosinusitis, asthma, and the emergence of a possibly major new therapeutic area in allergy treatment. Is DUPIXENT Regeneron's answer to Humira, this multi-indication, multi-blockbuster?
GEORGE YANCOPOULOS: You know, it's another area-- in order to make advances, many times you have to be really working at it for years, and years, and years. We've been working on this problem, in terms of allergic disease, for decades now. I've personally been working on it since the early 1980s. And I do think that we have literally hit upon the important pathway, or the sister pathways, that are critical perhaps for most, if not all, allergic disease.
GEORGE YANCOPOULOS: And the clinical data with DUPIXENT are proving that. So basically, right now, we have incredible clinical trial data now with DUPIXENT in a series of allergic disease settings, like you mentioned, whether it be asthma, whether it be atopic dermatitis, whether it be rhinosinusitis with nasal polyposis. Most recently, we reported our very positive phase III in eosinophilic esophagitis. Plus, we've shown that it can be important in fundamental basic allergies, such as in peanut allergy.
GEORGE YANCOPOULOS: So we believe that the targets of DUPIXENT, that is the interleukin 4 and interleukin 13 pathway, they may be-- based on the science that we and others have done over decades, they may be the critical drivers of fundamental allergic responses. And because so many diseases have an allergic basis, all of the ones that we mentioned and more that we're currently studying, it may be able to bring relief, and help, and maybe even be disease modifying for millions, and millions, and millions of patients.
GEORGE YANCOPOULOS: And it's an incredible story, I think. It's still a long way from being finished in terms of all the good that it can possibly do. But most importantly-- and this also goes with the biology, and also the genetics. A lot of the validation of these pathways came based on old, but also a lot of more recent work that's been done by Aris and the whole Regeneron Genetics Center-- is not only the importance of this pathway for the allergic disease, but also that it's not important for fighting most other forms of basic infections.
GEORGE YANCOPOULOS: So the safety profile of DUPIXENT makes it. It distinguishes it from Humira. And it distinguishes from, for example, JAK inhibitors. And it distinguishes it from most of other biologics that are trying to attack immune conditions. Because most of those result in immunosuppression, and then you're going to need something like our COVID cocktail to protect you from COVID-19. Or you're going to need other approaches where you're going to be susceptible to infection.
GEORGE YANCOPOULOS: So we treatment with Humira, treatment with other TNF blockers, all the sorts of these immune modulators, the ones for psoriasis, they all come with a serious immunosuppressive risk, and an increased risk of infection. The remarkable thing is you don't see that with DUPIXENT, because this pathway seems to be very limited, and limited towards allergic responses and not for fighting the most important infections that we have to worry about.
GEORGE YANCOPOULOS: So numerically, actually, infections in DUPIXENT treated patients, versus placebo treated patients-- for the conditions that you mentioned, most notably for atopic dermatitis-- you actually decrease the risk of infections. Because you now keep the immune system from being diverted towards a inefficient, inappropriate allergic response. Instead of diverting the immune system to wasting its time on creating useless allergic responses that are only harmful to you, you now allow the immune system to focus back in what it should be focusing on, which is on fighting infection.
GEORGE YANCOPOULOS: So you cure the allergic disease while actually benefiting your ability to actually fight infection. So in some ways, it's a better story, I think, than Humira.
ALEX PHILIPPIDIS: Aris, how does RGC play a role in DUPIXENT, for example, in its expansion of indications and in bringing that--
ARIS BARAS: Yeah, just as George touched on, so we now have genetic signatures. We can look at genetic variants in that pathway. And the first set of experiments were wow, they immediately line up with asthma, for example, right? But then you start to see other areas, other immune conditions, allergies that have genetic signal in this IL-4 pathway. So these are things that, as George mentioned, new genetics that can help us extend on what we know about that pathway, or sister molecules, sister pathways as George talked about.
ARIS BARAS: And in our pipeline, the itepekimab, or IL-33 program, and now that's in COPD, for example, right? And we use the exact same approaches, looking at genetics of IL-33, both gain of function that cause disease, loss of function that protect from it. And that really lined up the genetics to therapeutics approach in asthma and COPD. So it's really exactly as George described.
GEORGE YANCOPOULOS: Well, maybe a great story-- maybe this will be a great story to sort of, as a big finish here, is we've been talking about our approaches to come up with therapeutics, whether it be antibody approaches or others. Aris has talked about how we've incorporated genetics medicines through our collaborations with Alnylam or Intellia, such as siRNA or CRISPR approaches to attack genes. But we're constantly-- I mean, we're constantly working together.
GEORGE YANCOPOULOS: The people who are developing the therapeutics, who are doing the clinical trials, are working, for example, with Aris in the Genetics Group to understand the genetics basis of disease even when you have an effective treatment. And Aris and his team have just made, I think, an incredibly exciting and very logical finding in COVID-19, which, as you all know, we've just talked about it.
GEORGE YANCOPOULOS: We have an effective treatment. But they've realized a susceptibility locus that either helps protect you, or depending on your gene variation, or puts you at increased risk for getting COVID-19, which makes a lot of sense. And it only comes from their ability to have their genetics approaches. So maybe you want to touch upon that story, Aris. And that would be a great way to highlight how we do everything all together.
ARIS BARAS: Absolutely, no, and just like your message before, you know, this is one of those things where I think it's a paper that's just being submitted, or will be this info we put on the preprint. So I'm sure by the time we go live, this will be out there. But it's a logical culprit, looking at ACE2, the receptor that COVID requires to enter cells. And it was amazing. So we studied 50,000 people with COVID, and then hundreds of thousands of controls, and looking for what genes, what variants can lead to those who are getting very sick-- hospitalization, severe disease, death-- versus those that are just having a very mild, benign course.
ARIS BARAS: And so it turns out that you have to go big. You have to look at sequencing. You have to look at large numbers. But there are these very rare mutations that actually dramatically decrease the amount of ACE2 that you have on your cells, are those cells that express ACE2. And those people, just having one copy down, have about a 40% reduction in the risk of hospitalizations and severe disease.
ARIS BARAS: So it makes total sense, and really, the types of genetic discoveries we love to stumble upon.
ALEX PHILIPPIDIS: Kevin?
KEVIN DAVIES: Thanks, guys, just a couple of questions before we close. Aris, you've completed, I think you said, 1 1/2 million exomes-- there or thereabouts. How do you-- you've already given us a couple of examples. But how do you, overall, measure the ROI of that significant investment and effort? How is that information translated into the way that you manage clinical trials, stratify patient populations, and sort of pick winners and losers in the company's pipeline?
ARIS BARAS: You nailed it. So there's really only two ways. One is a very pragmatic one, and how are we doing in terms of new targets, in terms of our development programs, all the things you mentioned? And the other one is a little bit more open ended. And how are we doing in terms of advancing our scientific horizons at Regeneron, new areas that we didn't even know about when we started this whole initiative?
ARIS BARAS: So on the first one, it's been a smashing success. Len and George always told us, if we just get one-- just get one more PCSK9 or program like that, it'll be worth it. It'll pay it off, as you said, in terms of the ROI. And here we are today, something like-- depending on how you count-- maybe 12 or 15 new programs we've started, the most advanced ones that are in the clinic and are publicly known, like the Alnylam HSD17B13 program.
ARIS BARAS: But there's a lot behind it, and quite a few approaching the clinic. And as we talked about, in terms of things that are in development, we do a lot to help in terms of evaluating safety, or helping pick new indications, or helping identify biomarkers that enrich for those who are going to respond more favorably to our drug. But on the other hand, there are so many new areas that we explore.
ARIS BARAS: And we're committed to getting to 5 million, to 50 million people sequenced. We started this endeavor to find new targets. Now, we've got a whole new genetics medicine capability at Regeneron and amazing partnerships with some of the best in the world in these platforms. And perhaps, one of the new areas will be, we've realized that this data is incredibly powerful in terms of changing the way providers practice medicine, and the fact that the whole world-- the whole world of medicine at least-- really needs to get to an early detection model.
ARIS BARAS: We have to be able to detect things earlier. We have to be able to look at data, and to know with much more accuracy what risks-- what health risks someone's going to have. And then, how do you intervene in an earlier time point? And we're telling you, this data-- genomic data, and imaging data, and other molecular data-- are the key to do that in the future. And it's rapidly coming.
ARIS BARAS: The one analogy I like to offer, not in my day, but back in George's day when people could remember big supercomputers and we didn't have laptops at our-- everywhere, or--
GEORGE YANCOPOULOS: Days of the giants, Aris.
ARIS BARAS: Exactly, days of the giants whose shoulders we stand on now. But no, I mean, it's-- you cannot look anywhere in your rooms without a dozen example of Michael Electronics in that room, every street corner. And that's what's happening in medicine and genomics. It used to be, 10 years ago, that genomics was that supercomputer that George knew about. But now, we're rapidly get into a place where genomics is going to be ubiquitous in medicine, not in the areas that we've already established in therapeutics and all that, but just in how medicine is practiced.
ARIS BARAS: And so there are some tidbits on how we measure success, and how bright-eyes and how big we think about genomics.
KEVIN DAVIES: For both of you, we'd love to ask what new technologies are going to change either your particular corner of the company, or perhaps more broadly the face of drug discovery and therapeutics over the next 5 to 10 years. Aris, I'll start with you. And then maybe we'll give George the last word.
ARIS BARAS: Absolutely, so I've touched on them, really. I think that these capabilities in terms of RNA interference and CRISPR technologies, we have maybe less than a handful or so of approved therapeutics in the world from those technologies. But they're rapidly coming. And they're allowing us to unlock a lot of target space. So that's going to change the industry for sure. And I also think data-- what we're doing with genetics, what we're doing as a community with imaging, and machine learning, and AI-- that is unbelievable in its potential.
KEVIN DAVIES: George, would you like to follow that?
GEORGE YANCOPOULOS: Yeah, well, it's hard to follow that or add to that. But I do think that it's important to just highlight a couple of points, which is that, as I said, the history of Regeneron is marrying sort of technology with ideas. And the Regeneron Genetics Center is a great example of that. So what did they do? They married technologies.
GEORGE YANCOPOULOS: In most cases, it was a robotic space technology that was allowing them to now sequence at a scale that had never been sequenced before. It's not the sequencing machines that are the limiting thing, it's the process handling, and all of that that is still, in most places, done by human beings by hand. That they were able to actually automate and robotize that allowed them to work at a completely different scale, that then allowed them to create big data at a scale that was never generated before.
GEORGE YANCOPOULOS: And it was not only doing the sequencing, but finding the right populations of people to sequence, each one coming with their electronic records. Once they did that, to me, that is one of the biggest things that's been done in the biotech industry over the last five years. And as Aris says, he's only going to up the game by another order of magnitude or two, which is going to only further increase the information in the big data that we have.
GEORGE YANCOPOULOS: So big data is only as good as the data itself. And most big data that we have is not as amenable to machine learning approaches, and so forth, as is really this data that is well organized in a manner that can really be used in that function. So I think that this is going to end up being revolutionary. And we are trying to prepare for it, as Aris says, in two ways. One way is by turning this information into medicines.
GEORGE YANCOPOULOS: And what we recognize is that a powerful tool to turn them to medicines that we already had in our repertoire were the antibodies. So all of the targets, all of the genes that are working, that deliver products, proteins that are outside of the body we can address with antibodies. But there's a lot of these new genes, and discoveries, and big data that's pointing us to genes that we can't address with antibodies.
GEORGE YANCOPOULOS: And so this led us to make these critical alliances and collaborations with the companies that we thought were the leaders in the types of approaches, the new turnkey technologies after antibodies, that we're going to empower us to take advantage of all of the genetic targets that Aris and his team are discovering. And one of those is our major collaboration with Alnylam. So just like we were the best in the world at providing antibody solutions for our genetic targets, now working with Alnylam, we're going to be the best in the world at delivering siRNA solutions for our genetic targets, or within Intellia, CRISPR solutions, or with certain other collaborations, what we're doing internally, viral gene delivery solutions.
GEORGE YANCOPOULOS: So I think the biggest thing in biotech is creation of really important biotech big data, which Aris is generating-- the ability to turn into drugs based on our existing capabilities, but also these important, critical new alliances. And then the third real big opportunity that's going to come from the big data is what Aris just said, is applying all that information not only for drug discovery and to come up with the next great, important medicines, but to understand how to take advantage of that information so as to empower physicians so that they can actually provide better medicine based on existing solutions.
GEORGE YANCOPOULOS: Right now, no physician can possibly integrate all of the genetics information with all the clinical information and do justice to every single patient. Whereas, we think that by generating this data, and generating a solution that will allow them to do so, we may be empowering physicians with current solutions, let alone the new weapons that we're going to hopefully bring into their armamentarium-- a whole new age of healthcare delivery.
KEVIN DAVIES: Fantastic, if we've got 60 seconds, Alex, number 11, you had a good question, I think.
ALEX PHILIPPIDIS: Sure, what does Regeneron-- you mentioned working with Washington to get the antibody cocktail to India. What does Regeneron want to see or not see from the Biden administration?
GEORGE YANCOPOULOS: Well, I think that the most important thing-- and this is not for Regeneron itself-- is that we have to understand that there's nothing more important than incentivizing relentless innovation. Without that, literally the fate of humanity comes into question. We have true existential threats. They're not going to be solved by figuring out how to parse our savings, and how to control healthcare costs, and optimize that, and so forth.
GEORGE YANCOPOULOS: That's not what's going to save us, OK? To fight the existential threats of things like disease, future pandemics, but not to mention scourges that are going to come down in epidemic proportions like type 2 diabetes and Alzheimer's, we need new innovation to create new solutions for that. And the Administration has to recognize that there's nothing more important than the long-term solutions that can only be provided by new innovation.
GEORGE YANCOPOULOS: That requires much, much more investment. So whatever they're doing, they have to come up with a plan that does not decrease the investment and the incentivization that will bring forth the new discoveries and the new investments in technologies that will prepare us. As I said at the top, and this come full circle, the only reason the vaccine guys could employ mRNA technology to come up with these vaccines was because they had been investing in the technology, not for pandemic purposes, but for other purposes.
GEORGE YANCOPOULOS: The only reason we could come up with our effective therapeutic against COVID-19 is because we had been investing in these capabilities for decades, not to fight COVID-19, but to develop these technologies for other purposes. We have to recognize relentless innovation, incentivizing it. There's nothing more important than doing that. And I can only hope that this administration and future administrations recognize that.
KEVIN DAVIES: Thank you, George, great notes to end on. And that's all the time we have for this episode of Close to the Edge. Our sincere thanks to George Yancopoulos and Aris Baras from Regeneron for a fascinating discussion. I hope the rest of the episodes in this series live up to what we've just heard. For Alex Philippidis, my colleague, producer Jamie Cohen, and the entire GEN Edge team, thanks for joining us.
KEVIN DAVIES: I'm Kevin Davies. See you next time. Bye bye for now.
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The cadmore media player is a professional video and audio player experience designed to deliver media as well as relevant transcript, segmentation, and metadata. On the screen is a traditional html video player with buttons such as play, pause, forward, captioning, language and play speed selection and more. Adjacent to the video player are generally tabs, one of which shows a scrolling transcript of the video and the other shows any segmentation of the media, sometimes referred to as chapters. At the top of the video is a menu bar containing an Explore button and Tools button. The Explore button allows you to dig deeper into the video by opening up an explore dialog which contains tabs for a visual navigation of the video using thumbnails, an about tab which contains rich metadata about the media, a segments tab which contains further information about the video, and a related tab which contains links to other media related to this media. The tools button opens a menu with options for sharing the media on social media, creating bookmarking links, creating embed codes for your website, generating citations, and more.
Keyboard Shortcuts
Keyboard shortcuts only work while you are in forms mode. By entering forms mode, you will be able to quickly access portions of the media player with single key commands.
Spacebar: Play/Pause Toggle
I: Info Menu,
O: Tools Menu
T: Transcript Tab,
S: Segments Tab
F: Forward 15,
R: Rewind 15
L: Languages,
P: Playspeed
M: Mute Toggle,
V: Volume Bar
N: Video Only Toggle,
B: Full Screen Toggle
C: Captions Toggle
Escape: Closes dialogs and menus / Exits Player
Z: Next Transcript Chapter
X: Previous Transcript Chapter
Q: Next Transcript Paragraph
W: Previous Transcript Paragraph
Entire Media
Segment(s)
Custom Clip
Start At:
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Embed Size
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You Size - Responsive
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We Size - Responsive
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Picture Overlay Popup
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400 x 225
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512 x 288
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400 x 700
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768 x 1024
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1024 x 512
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1280 x 608
Form Title Cite
No citation provided.
Info
Segments
Related
Thumbnails
Exit Clip Mode
You have requested to see a portion of the video outside of the clip.
Click OK to switch to the full video or click if you would like to stay inside the clip. You can always go back to the clip with Tools and Clip Mode