Dr. Len Schleifer, CEO of Regeneron: Betting on Science and Saving a President

Given what we know about his condition and the virus, etc., they've had a very high probability of dying. When you save a penny life, it's important when you save the present of the United States that became quite the story. Regeneron is one of the oldest and largest founder-led companies in the S&P 500. It's up there with the giants like Invidia, Blackstone, Oracle, and Dell. It was founded in 1988 by Dr. Leonard Schleifer, its president and CEO, and Dr. George Uncopolis, its president and chief scientific officer. Len and George have been in their same roles for 38 years. They thought we were going to sell maybe 100 something in first-year, but we sold 800 million. And it seemed like, oh my god, this is the real deal now. Today we sit down with Len to talk about Regeneron's history, its key products, and how its deep pipeline will position the company for success in the future. I don't think we get any credit for our pipeline because if we take your revenue projections for DuPix, and you get all your value back from DuPix, and not to mention the $18 billion we have in the bank. Four investors buy an investor. Conversations with executives building tomorrow's great companies. You mentioned liver disease, and as I was going through your pipeline, you have a couple phase two assets for MASH. Yeah. Which ones you're most excited about? One's having to told you. Stay tuned. I'm Mike Rockefeller, CoChieve Investment Officer of Woodline Partners, and this is Inspired. All great to be here, Len. Good to have you here, Mike. Has it sunk in yet that you are coming up on 40 years since you founded the company? It doesn't seem like 40 years and one side, and on the other hand, sometimes it seems like a lot longer. But when you're doing something you love, time just passes. Take us back to 1988 when you started the company, what the vision was, and maybe how that has turned into what Regeneron is today. Yeah. It's been a long time, and you mentioned Warren Buffett, before you get the 1988. A couple of people, my family, keep track of who's the longest continued serving CEO of a large public company, and that was always Warren Buffett, Warren Buffett. I just ran into Warren at a conference, and I thanked them for retiring, because that moved me up in the longest serving CEO, continuously, with public company. Back in 1988, I had completed a lot of training. If you think about it, after college, I did seven years of training as the MD-PhD with a fellow by name of Alabama, Gilman, great, great mentor of mine, Nobel Prize winner, unfortunately passed away a few years ago from pancreatic cancer. But I had great training without, so I got my both my MD and PhD, and then I decided that I still wanted to be a doctor, a real doctor, not just a paper doctor, so I spent four years in residency with internal medicine training for a year, and then neurology training, where I became a board certified neurologist. I was on the faculty at Cornell. I was doing research, and a lot of grants, startup grants, NIH, American Heart Association. But as I was reading the literature, all the exciting work would seem to be about molecular biology. I had been trained as a molecular biochemist, not a molecular biologist. I didn't do gene cloning or any of that stuff. Then all the great papers seemed to be coming from this company, Genin Tech, or Genin Tech, and Genin Tech, of course, as they call themselves. I said, "What the heck is that?" I said, "That's interesting. They're a biotechnology company that are trying to come up with treatments for important diseases, taking advantage of the new science called molecular biology and molecular cloning." I had this notion about starting a company that would sort of try and imitate what Genin Tech was doing, but do it in the context of neurobiology neuroscience, because I was neurologist. I thought, "What were they working on? Things like human growth or a moan?" Then this company, Amjim, was coming along. They were working on EPO and Nupogen. I said, "Maybe the nervous system is just as complicated as that, a matter of poetic system." Frankly, I thought it was more complicated. There was only one nerve growth factor known at the time, NGF. I said, "You know, there had to be more. If we could clone them and make them and spritz them on people whose neurons were dying, maybe we could treat degenerative neurologic diseases." I started thinking about that. My mentor had called Al Gilman, I said, "What do you think about this?" He said, "It's the stupidest idea he's ever heard from me." He said, "He's heard a lot of stupid ones over seven years of training." But when he realized that I wasn't going to be talked out of this, he said, "All right, we're going to do this. Let's do it right." He recruited a couple of Nobel Prize winners, Brown and Coldstein and Arthur Cornberg and Eric Schu, we all got together and said, "Let's do this." So I started this company called Regenerant for Regenerating Neurons. The idea was to come up with new neurotrophic factors. The only problem was I wasn't a molecular biologist. Therein was a big problem because the way to get this was through molecular biology. We had this meeting of a bunch of scientific advisors. I said, "How can we get a molecular biologist?" Who's the brightest, smartest molecular biologist? They came up with some names. Fortunately, they came up with George and Coppola. At this time, the company was really nascent. George Singh, who was at the time, was at Merrill Lynch's venture capital, bet on us by putting a million dollars into the company. It was a big bet for George. He got a big chunk of the company for his firm. But he got us started. Believe it or not, George is still with us today on our board of directors. It's a great guy. I thought we had all the money in the world, a million bucks. Back in 1988 to start a company seemed great. The advisors I was talking to identified down Coppola, all we had to do was talk George into joining. Which wasn't the easiest thing to do. George wanted to do it, but I had to get past his dad as turns out. He was a child of very hard-driving Greek immigrants. And I remember George saying, "Let's have one more interview between us." I said, "Okay." I never had shown him we were going to build these labs so quickly, fast, and you could do an academia with literally on this campus. We took 10,000 square feet. That was our -- we now own this entire multi-million square feet campus. We had 10,000 square feet. It was from Union Carbide, who was sure the shrinking immediately post-Bopal. Anyway, the last interview I came up and George said we needed a restaurant and I couldn't seem in the restaurant. I saw two people sitting and I realized there was George and his dad. So I had to get past an interview. I was actually being interviewed rather than the other way around. But anyway, George joined and the rest is -- they say -- is history. That's interesting because looking at your company versus other founder-led companies, you actually have two founders who have been leading this company for 38 years. How has your relationship with George been so successful for so long? Yeah, it's a great question. I'm married for 51 years to my wife Harriet. She's my -- I would say my out-of-work wife. And I like to think of George as my in-work spouse. And the common theme is that in every relationship there has to be a Satan. I guess I'm going to argue that I'm the Satan. There's two relationships that are very long-lasting. Look, from the very beginning, I realized that there were two aspects of building this enterprise. One is sort of the science, the guts of the business, the molecular biology, cloning these things, doing the science. And the other was building the business around the science, funding it, you know, beg borrowing and what have you. They say to get the money. And I would say we've had a pretty healthy focus for each of us, sort of know what we have to do, but we rely on each other for what we do. And so I interact greatly with George on the science. He's a genius, so it's -- it's hard for me to keep up, but he interacts a lot with me on the business side and together. We've managed -- because we've had a common purpose. I mean, when common background, he's also an MD-PhD. And we knew what we wanted to do. We wanted to use science to make a difference in patient's lives. Were there any key decisions along the way that really changed the direction of the business? Yeah, there were quite a few. few. Remember that this is hard to believe, but for the first 25 years of our existence, we lost money every single year. And I'm not talking nickels or diamonds. I'm talking millions and billions. So for 25 years, we lost money. So the decision we made is despite a lot of people including the elks of people like you and the investment community, not you in particular, but the analysts, the investment community, our shareholders, even our board, you know, pick something focused and let's get it, of course, the finish line. And I think that the the best decision that George and I made is we weren't going to do that. We weren't going to bet the entire company. It always sounds great. It's Hollywood kind of a thing. You bet the entire company on something. Well, if we've done that, we'd been out of business. We were rather we were going to bet on the science, build the foundation of lots of different technologies and not fall into the trap of trying to bet everything on one molecule because we had NT3 and BDNF, George actually clone the first novel, no trophic factors since NGF. And we thought, you know, we were going to spritz it on patients with Lugaric's disease. We cure them. We get box seats at Yankee Stadium behind first base and sail off into that sunset in a matter of years. But obviously that didn't happen. But we kept saying we're going to survive. And when you meet up with the guy like George is pretty easy, you know, it wasn't a matter of if it was a matter of when. So I've just viewed my job as making sure we got to that when. What have been your top moments? At Regenerer? Yes. Yeah. My top moments at Regenerer. Well, you know, there were so many. It's hard to recount them. I mean, clearly just opening up the labs and realizing when we were in business was kind of amazing. The IPO in 1991, sort of a big moment, doing this multi-million dollar deal to really get us going with Sumitomo chemical, big moment, treating our first patient with one of our neurochromic factors, even though it didn't work out. That was sort of a big moment. But the defining moment from a business point of view probably came in 2011. We were sort of heading down the home stretch trying to get Ilya approved, which we had already approved arcolyst a few years before. But that was for a very rare disease. Although it's actually selling quite a bit right now, connects us, taking it over and doing a pretty good job there. But we had, we didn't have a significant product that could keep the company going. And, you know, 25 years people will run that at patients, I think. But in 2011, we knew we had the data. We'd submitted the FDA and sure enough, they gave us in the summertime a CRL. I can't even remember. We've had so many CRLs in years, recent years, and passed that, you know, it's hard to remember what they felt was missing at the time. I think it was something related to manufacturing again. But my dad at the time was 99 and a half. And he had been driving the car till he was 99. It was in great shape. But he started to go downhill in the fall of 2011. And we didn't get the drug approved. And he kept saying, "Lan, why are you going to get that drug of yours approved?" And right around thanksgiving, we got the FDA approval, and a few days later my father passed away. It was almost as though he was hanging on to see that happen. But that was a great moment, a conference, not great, obviously losing my dad. But seeing him being able to see our success at that age and knowing that we knew we had something. I remember going to the JP Morgan, I think it was called the Hamperton Quest Conference at the time, in early 2012. We had just launched the product. And people thought that we were going to sell, I don't know, $5 million. But we sold like in the first three months, something like $80 million. And then they thought we were going to sell maybe hundreds something in first year, but we sold $800 million. And it seemed like, oh my God, this is this is the real deal now. We're a real company. We're treating lots of patients. We're changing people's lives. That was pretty insurmountable times. It's funny when I was flying out to interview you, I told my kids, I have four young kids. And I said, I'm interviewing the CEO of Regeneron. And they said, oh, you know, who's that? What are they? And I said, well, you know, Ilya. And they said, no, we don't know Ilya. Do you pick, St. No. I said, do you remember when the president got really sick? And he got on TV. And he said he was feeling better because he took the Regeneron. I said, that's Regeneron. I said, oh, yeah. So that might be their top moment. That was a sample size. But that was definitely a top moment. That was an interesting story. I got a call from, I think it was Mark Meadows, who originally called from the chief of staff at the time. And they said they wanted to know, we had just announced, I think on the Tuesday, this was like on a Thursday, just announced that we had some really interesting data that we kind of knew this was going to work. This was a monoclonal cocktail for COVID. And they said that somebody in the White House wanted to get treated. Could we give it to them? I said, it's not the way it works. You can't just give an unapproved drug to somebody, some random person in the White House. You got to tell me more. And we got to see whether or not the person could qualify for a clinical trial, because we were very strict. We just weren't giving it out. We had to participate in our trials. That was the ethical and frankly moral thing to do. And finally admitted that it was the president. And that of course changed everything. And I said, look, we can't ask the president of the United States in the middle of a pandemic to participate in a clinical trial, come down to the site on Tuesday and we'll draw your blood and wait. It just didn't make sense. So we had to come up with a way that we could get him the drug. And I told him, the only way that could happen is if the FDA approved it and we haven't even asked them about it. They said, don't worry about that. We'll take care of the FDA. I said, well, you say that, but I got to submit it. And they said, that'll all be done within a matter of hours seemed like that was done. And I remember them saying, well, when are we going to get the stuff? And I said, well, it's been it was been packaged because it was manufactured in Winsley, New York. And we've charted a plane and we're going to send that plane down. Well, when's the plane going to get here? When is the kit? As I said, well, they're going to fly to Dallas and be Dallas. You got to fly to Reagan. It's much closer. I said, you can't just fly a private jet into Reagan. You know, this is post 9/11. You need 48 hours. Shoot out your pilot. Just head straight to Reagan. Watch this tail number. We'll have the military sort of part the way. So I knew this was the serious stuff. And then I had to deal with this wonderful doctor, Sean Connelly, who was the White House doctor? I mean, he wasn't equipped to deal with a president who was sick from a pandemic virus. Very nice guy. I had to tell him how he makes it. He hang the bivy. He get it in the blah, blah. And sure enough, we get it into him late Thursday night. At this point, it's been told publicly that given what we know about his condition and the virus, et cetera, that he had a very high probability of dying. And they moved him to Walter Reed shortly after they gave him the infusion in the White House. But it worked like a charm. Within 24 hours, he had turned the corner. And then, you know, sort of our lives changed a little bit because of sort of the publicity, you know, when you save any life, it's important. You save the president of the United States. It became quite the, quite the story. The bottom line is we were able to save a lot of lives. Yeah. And you did it very quickly. You mobilized. It was very impressive. Really amazing. Yeah. Maybe back in Ilya. So 2011, it got approved. Most successful ophthalmology drug in history. You got an approval for the HD. And so for many years, it was an important growth tire for Regenerade. Yep. Recently, we've had biosimilars with the 2 milligrams. So the franchises been declining. As you think about the next couple years, do you see this as sort of a stable business? Do you think there's a path back to growth? Yeah, I think there is. I think right now, we're at about 50, 50 in terms of our dollar sales and HD versus Ilead self, as that some of the Ilead gets eaten up by biosimba's coming along, but some is getting transferred to HD. So I think HD will be able to be a growth in and of itself. >> And then maybe on DuPix and your other blockbuster, your IL413, more than a blockbuster, I think it's one of the biggest drugs in the world. That's one of the top drugs in the history of the business. It's the most prescribed drug by dermatologist, pulmonologist, allergists, gastroenterologists, and terms of a biological. It's really, you know, it's taken off because it's a great drug. >> When did you start working in this area of type two diseases? So that was a long time before. George recently showed me some slides. I can't remember how far back. A long, long time ago, in some respects, before he even came to be general and he had thought about the switch factor in Ile 4. And he was an admirer of Bill Paul at the NIH, who had sort of popularized Ile 4 as a very important switch factor, changing IgG to IgE production. So it's probably a decade or two before, and then he started thinking about it. Even when it got a first approved, we had slides saying all these different conditions we thought that it would get approved. And then eventually the genetics sort of backed all this up that we had done this all right, because you could predict now with a genetic database what indications would work. >> So you have nine indications? >> Yeah, I can't even keep track of it. >> It seems like there's still a lot of penetration left to go in each of the markets that you're in. >> Yeah. >> And I'm sure you're hearing the cell side start to ask questions about the future of the drug. And some of them are saying that they think do picks and could do over 30 billion in sales by the end of the decade. Do you think that's reasonable? >> Well, it's polite and it's friendly and as much as I admire you, Mike, you know that I don't succumb to making predictions about future sales. Because I don't like to make predictions about things that I don't have any more information than you do. You can look at all the same information I have and you can make your best guesses. But I will say this, it's continuing to grow. It's annualizing, I think, based on the last quarter, just the first quarter of this year, just under 20 billion. It is not even highly penetrated. I think it's under 20% in eight tabletum, Titus and Les elsewhere. With new entrants, with Lillage products and other products, you're starting to actually expand a little bit. You're not fighting over the same market issue. We're actually all still growing this market. And we're very under penetrated in so many of the indications. I can certainly say I think growth being a growth driver is an easy bet. Yeah, I had to try. It does look like it's very possible. You also have some next generation antibodies in this same area. Which ones of those do you think will be most meaningful? Yeah, so once again, we don't try and make singular predictive bets because you start to fall in love with your own predictions. If you think the bets are going to win or the nicks are going to win the championship, you start to fall in love with that. And that's okay if you're a fan. But if you're running a business, you don't want to be a fan of your molecules. You want to make sure we bring all of them along and the best will rise. But so what do we have going as possibilities there? I mean, we have with Sanafi, they're looking at how to give more like with hyaluronidase, things like that, how to give more of the picks in so you can get a greater spacing between those is we have what we call soupi-dupi, which is a long acting version that targets the hyalurusceptor, same target as to pickson. That's not officially yet in the collaboration, but the rules of the road, if it's the exact same target, we can't develop it on our own and not the cutsanafi. So, you know, we're basically have to discuss if and how and when we put this into the collaboration, but that's coming along. And I'm sure we'll be able to work something out where we bring that forward. We have long acting isle 13, which we're moving along extremely rapidly, long acting isle 4, and we have some bi-specifix as well. So we have a whole pipeline of things. We also have new thoughts on we think we can cure allergy now. That's a bold statement, but I think we can back it up when we get our next generation of molecules, which I hope will be around the end of the year or early next year, into the clinic as a way to knock out ige cells specifically. I think we've sort of done some proof of principle there already. And so there's a lot for us to go in the type 2 immune space. You put up some interesting data with linozific and dupexen in severe fluid allergy. How come you're not moving forward with that one? Well, we did get a proof of principle there, but we think we have a better one, a better way of doing this. So the idea there was let's kill off the immunoglobulin producing cells. And we used BCMA by CD3, and that killed off all the immunoglobulin producing cells. The ige went down, the ige went down, the ige went down, and the concept was, well, let's prevent any ige from coming back by giving something like dupexen, which it worked. We could get 90-something percent of the ige gone and wouldn't come back, but it does take a long time for the ige to come back. George and the gang had something even better, which could destroy only the ige producing cells by some clever trick which we haven't told the world about. Which is not so obvious. So I think that we rather than spending a whole development program on something where we think a year behind it is something even better, you know, that's that's the luxury by the way of having a long-term perspective. The problem with this business, okay, is that number one it's hard, and number two it takes a long time. And number three it's very expensive. So the very expensive part comes from people like you pay for this innovation because we know that your opinions don't pay for the innovation. We can talk about that. But so if you're going to pay for it, the trouble is your time arises, maybe not. Mike has been around for a hundred years, but others of your ilk, you know, their time frames are much shorter. And so the question is how do you square a circle where the time to do really important things is measured in half decades and decades, yet the time that you guys work in are sometimes milliseconds occasionally or as long as you're which some of you can sit a long term as a minute. On the other hand, there is some that have been with us since our IPO who really do take a long-term perspective. We can't, if you succumb to those time pressures, this is why you wind up doing wrong bad things. This is why you get so many failures in our industry. It takes time to do things right. And you can't just say, well, I got to have one. If you got something better, you got to bring that along. So we have either the luxury, the wear with all or the foresight, whatever you want to call it, we're going to do things right. And if some take long of and others, that's okay. You have a very deep pipeline of over 50 things that you're trying to get right. So it's really exciting. Maybe just start on the on the late stage pipeline because you have some big phase three programs in areas like anti-coagulation, multi-miloma, complement. Which one of those you think is most underappreciated in terms of, we're generally changing the trajectory over the coming years. Well, and obesity, I think you've neglected. There's another big one. Once again, how I see the world may not be how you guys see the world. And I don't think we get any credit for our pipeline because if you look at what the, if we take your revenue projections for depicts and you get all your value back from depicts and not to mention the $18 billion we have in the bank. So there is a disconnect that people aren't paying enough attention to the pipeline. Let's start with obesity just because I think that you asked the way you asked the question, which ones are people ignoring? People are getting a little bit tired of hearing about the next obesity drug that has a little bit more weight loss or maybe it can be taken a little less frequently or Or maybe it's oral questions, how do you really, have you really changed the. this. And does it make any sense for you, General, to go in this game? Well, one of the ways to change it, we thought, was to invent a clip that could actually lower cholesterol at the same time as you lose weight. If you lose 50 pounds on Zeppond or Mangiro or Wokovic, whatever it is, you barely move the needle on your bad cholesterol. If your LDL was 150 when you start, maybe it's 145. It needs to go from 150 down to 50 or less. And so we wanted to invent a clip that not only caused weight loss, but lowered cholesterol. And of course, we realized we had one, which was prevalent. And if we could overcome a very hard technical task of getting these together, co-formulated in a volume, we could just give it the same way you wouldn't even know the prion is in there. Then effectively, we would have a drug that did both. And everybody misunderstands what we're trying to do here. We are not trying to sell more prion with this way. We can talk about how we're going to sell more prion when we talk about amg lost and an I trust jury case 400 million to us. We can talk about that market. But that's not what this is really all about. This is about selling a clip. And because we have a clip that now lowers your cholesterol. So you can take lilies clip where you can take novos clip where you can take somebody else's. But none of them are going to lower cholesterol. Why not take hours? And I think doctors will like that. And so we get zero credit for that. Even though we're well on our way here, we licensed a clip from hand. So by the way, in their study, they had much less GI toxicity than terseparatide did in a similar Chinese study. Yet had the same weight loss or more. So the question is, we think we have at least as good a clip. Maybe we got a better one, but when we combine it with prion, we have a total new class of drugs. It's as though we invented a clip that could also lower cholesterol. So you want to went to your doctor and you want to lose 50 pounds. And they said, by the way, if you lose 50 pounds, you still have to get your cholesterol down. But I have a clip that does both. Why wouldn't you take that? Especially if you could do it in the same injection and hopefully at the same close to the same price. How hard of a technical challenge is it combining those two? It was not easy, but we've done it. And when can you be in the clinic with that? Well, so we're in the clinic with the Ola that we have to get the way this works is that once you get that approved for obesity and for diabetes, then it's easy selling because we're just doing talking about a combination product. We just have to show that the PK hasn't changed and it won't. There's no reason. The hard part was doing the proprietary formulation and getting this to work together. That was difficult. And that was really unexpected what solutions this. So we have we own proud in the US and we have the proprietary, the patents on how to combine these things. So that loss is going to go very fast. We're rolling these trials. They they roll like butter obesity trials. So I think people are missing that completely. What else are they missing? I think that many have seated the myeloma space to J and J. They're formidable. We know them. They're really good at what they do. But at the end of the day in cancer, we think we have a better drug that's maybe more convenient. Perhaps less toxicity. We like our data a lot. We're going to commit and this is 30 or 40 billion dollar space. We're even thinking about monotherapy in front line. So we're very excited. You're going to see a ton of work come from us baking big commitment. They were obviously just recently got approved in the last line. We'll get some data next year in two plus. I would think we call it then we'll get some data after that in early stage. And we've even got data in light shine amyloidosis in high risk, small loing. This is a real big opportunity to simplify and change the paradigm. So that's that's a big one. I don't think we get much credit because everybody has seated that the J and J. These things can change pretty quickly. I don't think we're getting credit for our and a coagulant. Okay. That's a big mark. That is a that's another 30 or 40 or 50 billion dollar opportunity, especially because the number of people who actually take the dough ads is much lower than who actually should because of the fear of bleeding. And we have two entries to hit two antibodies. So like a one at one in one A if you will, if you're a horse racing person, you got to you get two horses in the race. Not just one with different characteristics. And so we're going to have, I don't know, between half a dozen and a dozen phase three going in all sorts of indications by this summer, some already underway, whether it's in post knee replacement, whether it's in cancer, whether it's in to act ineligible for for age of fibrillation, though eligible for peripheral disease or I mean massive big bet there. How are they different from the oral factor tens that are on the market and oral factor 11 stout are in development? Right. So if you look against the fact of tens, what we see from preclinical data is we can get the same or more in a coagulation and the genetic supports that with a much lower bleeding risk. The non catalytic side antibody has really a low propensity. We'll see if it even has an increase. And the other is very mild, but you get better in a coagulation. So once again, the do acts at the tens that just not used because of the this bleeding problem. In terms of the other factor 11s, if you look preclinically, you'll see that once again, you know, we just don't make singular bets. We make really good antibodies. We have better ant coagulation and no reason to think we'd have any difference in bleeding than either the small molecules or other antibodies. So maybe I should poison point something out. I will say this. I have watched our industry evolve since I got into this business in 1988. You know, you got a lot of value back in 1988. If you had a group of smart people and a prestigious scientific advisory board and an idea. And then this what I call the sliding lever moved along in different places. Sometimes you had to be, you had to have preclinical data. Then you had to have phase one data, say, then you had to have proof of concept and it kept sliding around. And then it's eventually what you got to have be in phase three to get value. Then of course, people realize, well, maybe you got to have a successful phase three. Then oh my God, you got to get past the FDA. And then you got to get it to be commercial. And then you got to get past the payers who are really difficult. And the Europeans who what I call the non payers. And then you got to worry about competition now from China and everywhere else. The world has changed. We had massive head start on to pick synth compared to the rest of the world. I Leah people in chasing I Leah for 10 years. No one's been able to come up at 15 years. No one's been able to beat I Leah. But I think those days are sort of numbered numbered in the sense that you won't have the kind of lead that you might have had if you come up with something out of the box because people catch up now so quickly. The tools are out there. So we like to get to two things. One is we like to have a lot going on. So instead of one 20 billion dollar product, maybe we have four or five five billion dollar products at a time where you know, it's easy to be more predictive and the who can do that? Only people who can put 50 things in the clinic with I'm not a half a dozen or more every year going into the clinic. So we think that that strategy of doing as much as you can broadly and accepting the fact that you'll have competition sooner is probably the best strategy that works. Now that's of course very self-serving Mike because nobody else does research like George and his team. So I think that we have a competitive advantage now in this new marketplace where building a company on one single blockbuster like a intruder or or Majaro or depicts it's going to get harder. Yeah, it does seem like you are getting more credit for your C5 franchise and MG and PNH but you've also put up great data there. Yeah, I forgot to mention that. That's the beauty of having so many things. Our C5 franchise, I think, has got the best in class data. We've shown that for P&H, you really need to push the limits a little further than just the antibody alone. So the antibody plus the SIRNA, we've shown, can really take people who are not fully controlled by looking at their LDH, for example, which is a measure of intravascular homolysis. We've shown that you can do better, so we're waiting for the final data on that. But we've already shown in my sting, however, she don't need all that. And just the SIRNA alone, which can be given quarterly and get the same kind of data, that's going to be, I think, a very competitive in a marketplace that's really growing. The one area that we haven't seen data for that franchise is in geographic atrophy, million patients in the US. A lot of opportunity. Big opportunity there. That's more speculative, I would say, but we have to do the experiment because they've shown that you work intravitually. We think most of the C5A comes from the liver, so you want to block this systemically. But we also have a plan to block an intravitory as well with a better cleaner antibody that's not pagalated and going to have some of these immune problems. So the reason these drugs haven't taken off is because they have these toxicities of these occlusive vasculitis and they may cause wet AMD to boot. So it's not been a clean class or they would have done a lot better, I think, because even though it's only at 20, 25% slowing, that's pretty important if you can do that safely, because you just don't want to have your retina to hatch at the age of 20. I mean, it's a big issue, so anything you can do to slow that down safely is a winner. So we'll see there. Once again, these are bets we'll make. We don't bet companies on these things, but with so many different ways to win. We have some really cool stuff we haven't talked about. I think we're going to turn the world a little bit upside down in some of a liver fat, fatty liver disease. Our genetics has given us approaches and ideas that are just, I think, going to sort of maybe revolutionize that space a little bit. We've got a genetics target that's given us a great leg up on cloud coma. We're looking at that. We've got another genetic target which we're starting very soon on shogun's disease and several other these phybrotic type immunologic diseases. I mean, it just keeps going and going. And we haven't even talked about our regenerangenetic center, which has got the largest collection of data, which is extremely interesting. And we've been struggling, but we're trying to come up with an idea. We've been struggling at a take at real advantage outside. I mean, we use it every day for discovering and developing drugs, validating pathways all that. But we think there's a health tech business there too that we can, because, you know, we have one of the largest databases in the world where you link genomics with, and soon proteomics and with electronic medical records. And with all the AI companies, I think it's going to be very interesting that how we can do this. Some cool stuff, by the way, you can do with proteomics. If we took your blood, we could tell you how old you are. Now, I could pick your pocket and look on your driver's license so that it's not that big of a deal, but we could do it from your blood. But we could also tell you not only how, when you were born, we can tell you how you've aged. So you might be 40 something, but you might be 60 something, because you haven't treated your body right or genetics and that's a good, or you could be 20 something. So you can find very interesting correlations between what's going on in your blood and what's going on in your genome. So for example, you might be a very high risk for Alzheimer's disease, but we can tell you whether or not you are despite this high genetic risk, whether you have 100% chance or a 0% chance of actually getting disease by looking at your blood. There's so many powerful things we'll be getting to realize when we start to study genomics, proteomics, and electronic health medical records. So trying to figure that one out too. You know, we do a lot, we're ambitious, but there's so much to do with so it's exciting. Yeah, you mentioned liver disease, and as I was going through your pipeline, you have a couple phase two assets for mash. Yeah. The ones I haven't told you about. Stay tuned. They're the leading mash company, Madrigal, just in licensed a PNPLA3 for mash from Arrowhead. And you have one as well in phase two. Is this an interesting target? Yeah, it is an interesting target, particularly for those who have this fairly common mutation. We know Bill Sibble, by the way, quite well. We like Bill, only know him from his days at Santa Fe. We work with him. Yeah. And he seems to have done a good job. You know, nothing lasts forever, Bill. Coming at you. You know, you're known for pioneering human monoclonal antibodies. That's, you know, I mean, you do it better than anyone. I would say George is known for that. George is known for that. He does it better than that. He's some credit also. Yeah. Interestingly, when you look at your pipeline now, a quarter of it is in SIRNAs. Yes. What is special about that modality that is a quarter of the Regeneron pipeline? Yeah, there are just, you know, targets. Well, let me back up. First of all, we love platforms. Monoclonal antibodies is platform SIRNA is platform gene editing is a platform and there were other platforms coming along that were very interested in. The main attraction of SIRNA is its ability to address targets that are not otherwise drugable easily, let's say, by a monoclonal antibody or even a small molecule. So that's what's particularly. I think people do tend to misuse technologies. You know, TTR is a good place to use it. Putting an SRNA and AI to try and lower Vagiav would be a dumb thing to do. But there are places where you really can't get to targets where SIRNA can get you there. And we've been working with an island on some CNS targets, which are very interesting. I can never remember which ones we've told you about, which ones. We haven't so won't get myself in trouble. But that's the main advantage. You can quickly try and address targets. And of course, they remarkably and openly would have believed that they had this incredible long half-life that they can work. Anything in the early pipeline that we should be asking you about? You know, I won't get much credit so why bother to educate through SIRNA? I think I'm through an atchic glaucoma. The fibrodech, immunologic disease, the show grin and others. That's a very interesting one. I told you that we got something really interesting in the the MASH world. We got a lot. I mean, we put half a dozen of more every year into the clinic and 50 in the clinic. So, and by the way, we haven't talked about what we're very proud of is our curing kids with profound deafness. There's a gene called Otoferrolin, which was first discovered in the 1990s, just Georgia, how long science takes by a woman whose name I forget at the pastor institute, but there are about 50 kids a year born who are missing this protein. And if you haven't had this protein in your hair cells in your inner ear, you could put a jet engine next to these kids and they hear nothing. And our gang, we first got involved in the you know, we were working with Tessabell. We brought Tessabell inside, but you know, and they've been great collaborators. But our team together with them, we were able to figure out how to package a very complicated, very large gene and get it into into children and amazingly, amazingly. This is truly science fiction. Okay. This kids can now hear almost half of them can hear a whisper in here normally. And we made the decision we were given away for free because every once in a while, you have to show the world that the bio pharmaceutical industry really cares about what it does and cares about the people that it serves. And we'll get a lot out of that in terms of we have learned how to maybe address bigger problems, more commercially viable, but we're very proud. And I can't say how well we see that's been amongst our scientists, how many how it's increased people want to come work for us. These are all sort of byproducts. But it was the right thing to do and we're proud we did it and I think it's a good statement. It was amazing seeing that child at the White House. - Yes, really amazing. - Yeah. - You had talked about Regeneron's Genetic Center and you're a leader in technology and data. How are you using artificial intelligence right now in your R&D? - Yeah, so two ways. One is the obvious way that any business could use. If you got to write a protocol that's this thick, well, AI can write a first draft of that in a minute, okay? Rather than have somebody prepare me for Rockefeller's hard questions, I can ask AI to do it. That kind of, what I call, quote unquote, busy work is what AI is particularly good at. But if you know how AI works, and I've got a real lesson from this from George, because he thinks about this stuff, and he really, his soul is intuitive to him. I have to think it hard, but it's not really thinking. It's statistically putting things together just based on what it's trained on. But, and it might come up with a new drug based on a small molecule, scaffold or something. But do we need it to design an antibody? No, we got our humanized mouse, it makes human monocle antibodies by the thousands. And in fact, the AI people all came to us wanting to get access to our collection of structures and antibodies so they can train. I mean, so we don't use it to discover the actual drugs, but we use AI in our genetic sense that to find the right correlations, what's the right relationship, and it can do some of these big data tests faster and more powerfully than old methods could do that. Do you see that evolving over the next several months or years? Yeah, I think that we're looking about how to take advantage of AI and our data set. These millions of people and see if we can't get more into the management of health care not just by drugs. Interesting. M&A, so you've taken, I would say, a different approach versus a lot of your peers, which is just focusing on technologies and platforms, as you mentioned, often early stage, smaller deals. Do you see that strategy evolving as the company continues to scale and grow over the coming years? Yeah, it's a good question, Mike. I don't think our strategy will evolve because I don't think it has devolved or it's never really changed. We are interested in any and all opportunities. We prefer things that are platforms. We prefer working with people who are like-minded and want to work with us where we can be additive together and one-on-one can literally make three. We want to make money in what we do. This notion that this is free because you're taking from your balance sheet and you can non-gap it or do something, all that to us is maybe a driving factor. People talk about their M&A capacity. I don't think of that as a proven strategy to destroy value. You show me companies that have done that well. The one that's done at the best once, which is Sanafi with 2pixit. They'll admit that. That was a great partnering kind of a thing. But competing for late stage or approved assets, there's not much to that because you're spending $10 to turn it into $6 frequently. And that's because people are so desperate. We literally have seen things that we thought were worth just to pick an arbitrary number six and people willing to pay 12. That's just crazy for us, especially because we have such a rich pipeline of our own. So if there was a great asset, I mean, we've got $17, $18 billion in the bank. We've got a lot of capacity. If there was a great asset that we saw, valuing that others didn't, yeah, we would do it. We're not constrained by size. People don't really understand how all this works. We don't tell new out of the seniors that great had a BDNA. This is what you can spend this year, go out and spend it and we're desperate for a phase three or something like that. We just look at the whole universe of things and what makes sense for us. And I just think it's a formal rational way of doing that. And to me, you should view all this as one. That is, our goal as a company is to get products that make a difference to people and that will help people and it'll help our shareholders. If it comes from our research, which is most likely for us, that's more efficient, more predictable. But if we have to go outside, we have no problem with that. So could a large deal or even a merger ever make sense for a company like our genre? Sure, but it have to be value creating. And that's the hard part. It's unlikely, but there have to be something that we see that's not visible to others at a price that makes sense compared to what others are willing to pay. And we've been involved in some of these midsize kind of discussions, but everybody pays these crazy numbers. It does make any sense. Yeah. So you've been leading this company for almost 40 years. What does the next chapter look like for you personally and for the company whenever that time comes so that you can ensure that we're generally on and it's culture and doors? Yeah. You know, found a lead company's really like our different. George and I have been leading this company for a long time. And it is our life's professional work. We do this 24/7. We slightly keep different hours. So when I'm at home, George's maybe still in the lab or coming home, he's calling me or I'm calling him when he has and we're talking all the time and we're loving what we're doing because we were just so excited about the prospects of it's like living the dream of making a difference in people's lives and doing that in a productive way with the appropriate financial rewards. I think it's great. But no man lived forever. And so we are developing talent on a constant basis. I want to do it. I know George wants to do it as long as we feel we can be the best people to be in the jobs that we're in. And when we're not, we'll have a deep bench of people that I think can take our place. But I like to think that things are, there's a way about doing things. There's an ethical approach. There's a patient first approach. I mean, I hear about some of these companies that, you know, I won't use names of people who have FDA wants to withdraw a drug because the data was manipulated and according to the FDA and there's safety concerns. And it's still fighting whether or not to take it off the market. It's like they're in the widget business to me. I mean, they must have their own perspective on these things. But there are companies like that. That's not who we are. We like what we're doing. We can, I think we're still doing it well. I don't think that people fully appreciate the difference the way a founder-led company is managed versus the what I, you know, we're not renters or owners, so to speak. You know, you have a CEO or a CSO. They don't only have about a five-year rise and something like that. You know, let me see how's that work within it, at San ify, by the way. How many? Eight. Eight. Wow. So, you know, that's not who we are. And so we like what we do and we think we're good at it and we want to keep going. But as I said, we'll know when it's time to let the young bucks take over. You've done an incredible job. Before I let you go, what advice would you give to the next Len who was thinking about leaving the lab and starting a company? Well, I think the first thing I would do is find a George. That may be impossible because it's probably, they probably broke their hold. But in terms of general advice, I would have to say, you've got to have the right, the long-term perspective, do not make singular bets, ignore all the stuff that you hear from the analysts. And I used to get in my early days. And sometimes I still do it because I can't resist a good fight. But some of the analysts who have these crazy views of each and all, you just got to ignore all that noise. Even the shareholders, you can't ignore them. But you have to educate them that we're not here to make you money this quarter. You want to bet on whether or not when we turn over a trial. That's your business and that's OK. And you can make that wager with any ways that you guys can make those wagers. But I would say to somebody, focus on the long-term, focus on the science, focus on what you're really trying to do is make a difference to patients. You really are not in the widget business and have a really strong moral compass. They're gonna be some damn-- times where you've got to be willing to say this is not right. I'm not going to do this. And you've got to resist all those pressures. Great advice. Thank you for all you've done for patients and for shareholders. I appreciate the time. Thank you Mike. It's been a pleasure knowing you. You've been doing this but that case but you don't look like you've changed. So neither do you. Kudos to you. So we have a couple more years left in us. Yeah. Hope so. Great. Great to see you. Thank you.