How Two Doctors earned more than $1 billion on Mutations
The X-Men Cure
In Germany, in Berlin, a small child with incredibly developed muscles was admitted to the hospital. He is four years old, but he can hold a three-kilogram dumbbell in each outstretched hand.
Such people, genetic mutants, as if they came out of the stories about the X-Men, are not just gifted by nature. They open the way to the future of human health, along which 53-year-old George Yankopoulos, Director of Science at Regeneron Pharmaceuticals, is moving forward. The medicine he developed, based on the study of heart mutations, is one of the most remarkable innovations in pharmaceuticals. Another medicine, created after studying the very baby Hercules, can help cancer patients whose muscles weaken. Yankopoulos' other drugs – for asthma, rheumatic arthritis and cancer – are now undergoing clinical tests. All of them are based on a unique method created by his team – they inject large chains of human DNA into experimental mice, and then quickly create drugs for people based on the data obtained.
Three of Yankopoulos' drugs have already gone on sale, and this is an amazing achievement for an industry in which scientists work all their lives developing one drug, and if they manage to create two, then they are treated like superstars. Alas, two of the three drugs turned out to be commercial failures: a drug for a rare genetic disease and an oncological remedy. Therefore, great success came to him only at the end of 2011, when the Eylea drug went on sale, which makes it possible to treat the main cause of blindness in adults. Sales of this drug in 2012 amounted to $838 million, and this year it is expected that revenue will reach $1.3 billion.
But Regeneron has become one of the most innovative companies in the world (this year they took fourth place in the Forbes list) not only because of successful scientific developments. At least the second half of the success belongs to the founder and CEO of the company, Leonard Schleifer, who has supported Yankopoulos for two decades. Schleifer is 61 years old, he is a doctor by education and at the same time one of the most visionary businessmen specializing in biotechnology. "George was too talented," says Schleifer, "he was surrounded by talented people. There was no question whether we could do it. The question was when we would be able to do it."
George Yankopoulos and Leonard SchleiferAnd they were able to do it, and brought new drugs to the market with minimal costs.
An analysis by Forbes of 220 medicines, for the production of which public companies have received permission over the past ten years, showed that those companies that created three or more drugs spent an average of $4.3 billion per drug on research and development. The costs of large corporations are even greater: Merck – $5.5 billion, Pfizer – $7.8 billion, Sanofi, Regeneron's partner in many projects – and $10 billion at all. How much did Regeneron spend on one medicine? Only $736 million.
As a result, Schleifer is about to become a billionaire. Its capital, mainly consisting of Regeneron shares, is estimated at $800 million. Meanwhile, Yankopoulos has made more money than any biologist in history. Last year, he received a compensation package of $82 million, also mainly in the form of shares, thus overtaking all the heads of American corporations with the exception of Larry Ellison. Yankopoulos' fortune is estimated at $400 million.
But despite his medical and financial success, Yankopoulos has yet to create a drug that will truly change the world. His new projects – medicines for heart disease and asthma – may be the means that will save thousands of lives. During my visit to Regeneron headquarters, I saw what a person who literally lives in a laboratory looks like. Gray stubble was next to a Van Dyke-style beard, the laces of his Oxfords were untied, and a hole was visible on his shirt. The blackboard in his office was covered with notes made by his children who visit him at work.
First stepsRegeneron was actually born in a Chinese restaurant.
In 1988, Schleifer, who was then an associate professor of neurology at Weill Cornell Medical College (part of Cornell University), scribbled on a napkin the terms of a deal with the venture division of Merrill Lynch and left the restaurant, having received an investment of $ 1 million, the position of CEO and a new company that was supposed to treat diseases of the nervous system.
One of the consultants told Schleifer about the "young superstar of his generation" – Yankopoulos, who was 28 years old at the time and was already a professor at Columbia University. Yankopoulos had a unique reason why he decided to listen to Schleifer. His father, a Greek immigrant who came to America hoping to earn a fortune lost under the Nazis, was outraged that his brilliant son chose such a poorly paid academic job for himself. Yankopoulos received grants of $2 million for eight years, but according to their terms, his earnings were only $35,000. My father said that America should pay him a lot more.
Yankopoulos was already looking for a possible location for the future Regeneron laboratory, but could not make a final decision about working with the Schleifer. In the end, he came to a meeting at an Italian restaurant with his father. "I was going to persuade George, but his father decided to interview me," says Schleifer. The father gave the go-ahead, and Yankopoulos signed the contract.
But eight scientists who agreed to work with Yankopoulos at Columbia University did not want to follow him. In those days, working for a corporation actually put an end to an academic career. Yankopoulos had a laboratory with an area of 930 square meters, but he could not find anyone who would agree to work in it. Yankopoulos hired his first employee, an unemployed theoretical physicist interested in biology, only a few months later, and created the core of his research team two years later.
At first, the road to fame seemed simple. Yankopoulos found out that the growth factors that accelerate the healing process were contained in the brain in the same proteins as in the rest of the body. It is necessary to isolate one of them, put it in the brain of patients, and – rrraz! – the company will help patients suffering from amyotrophic lateral sclerosis. Schleifer already imagined how they would triumph and start counting their money while the lives of their patients would change for the better. Instead, the drug failed clinical trials.
A dejected Schleifer made an unexpected offer to Yankopoulos: "Why don't we invite Roy Vagelos. Maybe he will help us get out of this situation." The idea was audacious. Vagelos then headed one of the largest pharmaceutical corporations Merck and was one of the most famous and respected leaders in the history of the pharmaceutical industry. They were lucky – Merck began a management reorganization, and Vagelos decided to leave the company, so he agreed to meet with young businessmen.
Yankopoulos worked all night after the corporate holiday party and prepared a presentation. Vagelos liked what he saw: he became chairman of the board of directors of Regeneron. "This company has a great CEO and a great director of science," says Vagelos, "and, you know, this symbiosis is the whole essence of working in our industry."
After that, there were new failures: a second drug for amyotrophic lateral sclerosis and a drug for weight loss. And then there was a breakthrough. Yankopoulos and his team have figured out how to turn cellular receptors into "traps" that will stop growth factors in the blood.
The first "trap" launched by Regeneron treated a rare kidney disease, and in 2008 it blew up the market. The drug paved the way for other successful drugs – Zaltrap and Eylea. After Eylea was approved for sale in November 2011, Regeneron's stock soared by more than 400%.
Experiments with mutationCatching growth factors and creating drugs-"traps" were only the first step.
According to Yankopoulos, the key to the creation of new medicines are technologies that will facilitate and accelerate the process of their development. To do this, he needed as accurate data as possible on the effects of the drugs being developed on the human body. The problem with laboratory mice, on which primary experiments are being carried out, is very simple: they are not human, and despite the amazing number of genetic coincidences, their little bodies do not always act in the same way as human ones. It is well known that drugs that reduce tumors in mice do not produce the same effect on humans, and a whole chain of drugs for blood diseases failed because the immune system of mice turned out to be different from ours.
Then Yankopoulos and his team developed a method for embedding up to 6 million characters from human DNA into the mouse genome. As you know, many drugs created in the era of biotechnology are antibodies, a kind of cunningly constructed bombs that the immune system uses to neutralize pathogenic microorganisms. These drugs are traditionally made with the help of mice, and then they are gradually changed, one amino acid after another, turning into those antibodies that the human body accepts. But in Yankopoulos' mice, part of the immune system was replaced by human genes, which led to an acceleration of the drug creation process.
The French corporation Sanofi (one of the leaders of the pharmaceutical market with revenues of €35 billion) assessed the prospects of Yankopoulos technologies and since 2007 decided to invest $100 million annually in Regeneron research projects in exchange for 50% of the profits from drugs made as a result of these studies. In the first two years, five drugs reached the testing stage, and then Sanofi increased funding to $160 million per year, and also assumed the main costs of clinical trials, marketing and promotion of new drugs.
The next step of Yankopoulos: for the best use of his technology, we need not mice, but mutants. How will it work? Take a look, for example, at a gene called PCSK9, which was first discovered in France in patients with super-high cholesterol levels, which already at a young age put them at risk of a heart attack. Researchers from the University of Texas Southwestern Medical Center examined a huge database of heart disease patients in search of people with low cholesterol. They found out that there is a group of people with one corrupted copy of the PCSK9 gene who have a 28% lower cholesterol level and an 88% lower risk of heart disease. There are also a number of people in the world who have two PCSK9 genes corrupted, among them the aerobics instructor mentioned at the beginning of the article with super-low cholesterol levels. They are all healthy, but they have a low-density lipoprotein level of 15 mg per deciliter, while in most healthy people it is 100 mg.
In simple terms, the logic of scientists looks like this: when the PCSK9 gene manifests itself, it is bad, when it fails, it is good, and if there is a drug that blocks this gene, it will help the human body. Regeneron and Sanofi want to conduct clinical trials, but are patients willing to give injections for the sake of cholesterol control? According to cardiologist Steven Nissen from the Cleveland Clinic, a real success awaits the drug only if it is proven that it reduces the likelihood of heart attacks and heart attacks much better than statins, which today are cheap general medications.
Yankopoulos is working on several drugs at once, but he himself is most excited about a drug that will allow him to treat allergies and asthma – diseases that, according to him, he almost never encountered as a child. And, of course, Yankopoulos is looking to the future. In his opinion, the ability to decipher human DNA cheaply opens the way for many new experiments. Will a new breakthrough in medicine begin? We'll find out in time.
Portal "Eternal youth" http://vechnayamolodost.ru02.10.2013