N E W S & A N A LY S I S AN AUDIENCE WITH…
Mads Krogsgaard Thomsen Although the biopharmaceutical industry has undergone waves of change and disruptive mergers and acquisitions (M&As) over the past two decades, Mads Krogsgaard Thomsen, chief science officer at Novo Nordisk, has enjoyed relative tranquillity during this time. This year, he celebrates his twentieth anniversary overseeing research and development (R&D). During his long tenure, the veterinary scientist turned pharmacologist has helped Novo Nordisk become one of the top diabetes drug companies by spearheading the optimization of insulin analogues and by championing GLP1 analogues. He talks with Asher Mullard about some of the mistakes he’s made and the lessons he’s learned from his time at the top. You started heading up R&D at Novo Nordisk when you were in your early thirties. How did you get the position? Novo Nordisk was actually headhunting for a head of diabetes research, and I was one of the people interviewing external candidates for the position. But having somebody come in from the outside to lead R&D can be difficult, so the leadership invited me for an interview and then appointed me as head of diabetes R&D in 1994. Then in 1995 they decided we should centralize our approach to R&D, and I became head of research in general. Now I am responsible for around 6,000 people, so my job probably demands a little more maturity. But the company was smaller at that point, and it took some big chances. It placed some bets on me and a few other young colleagues of mine, and we are still there. Now I perceive myself as the experienced guy, but at that stage in my career my strategy was to team up with the experienced folks who were present throughout my organization. I probably made an awful lot of mistakes, but also learned a lot. What’s been one of your biggest mistakes? At one stage we launched a major medicinal chemistry effort, thinking that we could take on Merck and GlaxoSmithKline and all the big companies in the small-molecule arena because we thought we were the people who understood diabetes. Only later did we realize that we were actually the people who understood protein design and how to make superior analogues of human proteins and hormones. That is, we are a technology-driven company directed by our protein know-how more than we are a biology-driven company that understands all aspects of diabetes.
When we realized this, we re-deployed our medicinal chemists to help us fine-tune our biologics. We’d learned that by adding fatty acids and small-molecule ligand side chains to our biologics, we could make them longer-acting, make them bind to albumin or do all kinds of other exciting things. Liraglutide, for example, was actually produced by two people: a scientist who understood the protein and a medicinal chemist who attached a fatty acid to the molecule so that it would bind to albumin and circulate in the bloodstream for 24 hours or longer. This general approach has given us an array of new modified proteins that really make a difference. We are now one of the only companies that combines protein backbone design with the addition of side chains through medicinal chemistry. But this came from our failure to compete in the small-molecule space. How long did it take you to realize that mistake, and learn from it? We started the medicinal chemistry drive in the mid‑1990s, and only realized after we had seen all our failures that we were not ahead of the game. The full decision to exit small molecules was made around 2006. The benefit of having a sustainable business, though, is that we can allow ourselves to make long-term bets. What long-term bets are you making now? We still have the dream of making oral antidiabetics, and started a potentially transformational project a few years ago to turn our biologics into stable molecules that can be administered as tablets. Right now we are optimistic because we have just advanced an oral GLP1 project into Phase II trials.
96 | FEBRUARY 2014 | VOLUME 13
Novo Nordisk
We also have a big effort to find new molecular mechanisms — new receptors that we can stimulate with modified analogues of the natural human proteins or peptides — for the treatment of type 2 diabetes, type 1 diabetes or even obesity. If you look at the recent scientific literature, you will find that many of the hormones and other factors that the human body produces are short-lived, with half lives on the order of only a few minutes. If we can use our technology to stabilize these, then we can turn them into human therapeutics. I would love to see a new field like the GLP1s emerge, either in diabetes or in obesity and metabolism. Around 6 years ago, we also realized that we were in control of our core areas — diabetes and haemophilia — and had scope to expand our focus. When we matched our core competencies with new areas of research, we realized that we could move into autoimmune disease: we were already working on type 1 diabetes, and we had experience with injected biologics. We now have a handful of exciting molecules, some of which are currently in Phase II trials. Our strategy here is to only go for first-in-class products. Industry as a whole has seen a fair amount of churn and reorganization over the past 20 years. What has been your approach to restructuring and reorganizing R&D over this time? It has been an evolution, and I have reorganized at multiple times to adapt to different situations. But I have tried to avoid reorganizational turmoil and layoffs. I have only been involved in one layoff process in 1999, after we lost the royalties for a major www.nature.com/reviews/drugdisc
© 2014 Macmillan Publishers Limited. All rights reserved
drug. It taught me one thing, and that is that if there is anything that is disruptive to an R&D organization then it is the uncertainty and demoralization that occurs with a major downsizing. Every time management goes out and streamlines the pipeline — a buzzword for eliminating projects — they are not enhancing R&D productivity but decreasing it in my view. Fortunately, because we have exhibited constant growth since then, we have had a lot of continuity and much more momentum in the intellectual property (IP) arena than many of the companies that have gone through multiple rounds of M&A activity. Scientists are very proud people who want to do their research. But they are susceptible to emotional stress. They are not hard-nosed sales and marketing folks. They need to have a lot of freedom to get on with their job without too much management interference and without too much of the turmoil that comes with disrupting an organization through multiple reorganizations or layoffs.
I probably made an awful lot of mistakes, but also learned a lot.
Another industry-wide trend has been the increased investment into R&D in Asia. You were one of the early companies to test these waters. What you have you learned from this experiment? When we inaugurated an R&D laboratory in Beijing in 1997, we didn’t quite know how to start so we initiated a high-throughput testing project of Chinese herbal medicines to try to identify molecules that we could use to treat diabetes. We did identify quite a few active molecules, but they always turned out to be a known class of agents that was in the pipeline or on the market. This taught us, though, that our Chinese scientists were extremely dedicated. I realized then that they needed to do something else, so we focused them on optimizing our protein production strains. I wanted them to work on something a little precompetitive. We didn’t have them designing new insulin or protein analogues, because we tend to keep those to ourselves in the headquarter-based research laboratories. At that time in China, we were never quite sure about how IP and ideas would disseminate. Since then, as the IP concerns have become slightly less controversial, we have started to give them more research project leadership responsibilities, and they are running a range of exciting projects in collaboration with research laboratories in Denmark and the United States.
NATURE REVIEWS | DRUG DISCOVERY © 2014 Macmillan Publishers Limited. All rights reserved
Mads Krogsgaard Thomsen Although the biopharmaceutical industry has undergone waves of change and disruptive mergers and acquisitions (M&As) over the past two decades, Mads Krogsgaard Thomsen, chief science officer at Novo Nordisk, has enjoyed relative tranquillity during this time. This year, he celebrates his twentieth anniversary overseeing research and development (R&D). During his long tenure, the veterinary scientist turned pharmacologist has helped Novo Nordisk become one of the top diabetes drug companies by spearheading the optimization of insulin analogues and by championing GLP1 analogues. He talks with Asher Mullard about some of the mistakes he’s made and the lessons he’s learned from his time at the top. You started heading up R&D at Novo Nordisk when you were in your early thirties. How did you get the position? Novo Nordisk was actually headhunting for a head of diabetes research, and I was one of the people interviewing external candidates for the position. But having somebody come in from the outside to lead R&D can be difficult, so the leadership invited me for an interview and then appointed me as head of diabetes R&D in 1994. Then in 1995 they decided we should centralize our approach to R&D, and I became head of research in general. Now I am responsible for around 6,000 people, so my job probably demands a little more maturity. But the company was smaller at that point, and it took some big chances. It placed some bets on me and a few other young colleagues of mine, and we are still there. Now I perceive myself as the experienced guy, but at that stage in my career my strategy was to team up with the experienced folks who were present throughout my organization. I probably made an awful lot of mistakes, but also learned a lot. What’s been one of your biggest mistakes? At one stage we launched a major medicinal chemistry effort, thinking that we could take on Merck and GlaxoSmithKline and all the big companies in the small-molecule arena because we thought we were the people who understood diabetes. Only later did we realize that we were actually the people who understood protein design and how to make superior analogues of human proteins and hormones. That is, we are a technology-driven company directed by our protein know-how more than we are a biology-driven company that understands all aspects of diabetes.
When we realized this, we re-deployed our medicinal chemists to help us fine-tune our biologics. We’d learned that by adding fatty acids and small-molecule ligand side chains to our biologics, we could make them longer-acting, make them bind to albumin or do all kinds of other exciting things. Liraglutide, for example, was actually produced by two people: a scientist who understood the protein and a medicinal chemist who attached a fatty acid to the molecule so that it would bind to albumin and circulate in the bloodstream for 24 hours or longer. This general approach has given us an array of new modified proteins that really make a difference. We are now one of the only companies that combines protein backbone design with the addition of side chains through medicinal chemistry. But this came from our failure to compete in the small-molecule space. How long did it take you to realize that mistake, and learn from it? We started the medicinal chemistry drive in the mid‑1990s, and only realized after we had seen all our failures that we were not ahead of the game. The full decision to exit small molecules was made around 2006. The benefit of having a sustainable business, though, is that we can allow ourselves to make long-term bets. What long-term bets are you making now? We still have the dream of making oral antidiabetics, and started a potentially transformational project a few years ago to turn our biologics into stable molecules that can be administered as tablets. Right now we are optimistic because we have just advanced an oral GLP1 project into Phase II trials.
96 | FEBRUARY 2014 | VOLUME 13
Novo Nordisk
We also have a big effort to find new molecular mechanisms — new receptors that we can stimulate with modified analogues of the natural human proteins or peptides — for the treatment of type 2 diabetes, type 1 diabetes or even obesity. If you look at the recent scientific literature, you will find that many of the hormones and other factors that the human body produces are short-lived, with half lives on the order of only a few minutes. If we can use our technology to stabilize these, then we can turn them into human therapeutics. I would love to see a new field like the GLP1s emerge, either in diabetes or in obesity and metabolism. Around 6 years ago, we also realized that we were in control of our core areas — diabetes and haemophilia — and had scope to expand our focus. When we matched our core competencies with new areas of research, we realized that we could move into autoimmune disease: we were already working on type 1 diabetes, and we had experience with injected biologics. We now have a handful of exciting molecules, some of which are currently in Phase II trials. Our strategy here is to only go for first-in-class products. Industry as a whole has seen a fair amount of churn and reorganization over the past 20 years. What has been your approach to restructuring and reorganizing R&D over this time? It has been an evolution, and I have reorganized at multiple times to adapt to different situations. But I have tried to avoid reorganizational turmoil and layoffs. I have only been involved in one layoff process in 1999, after we lost the royalties for a major www.nature.com/reviews/drugdisc
© 2014 Macmillan Publishers Limited. All rights reserved
drug. It taught me one thing, and that is that if there is anything that is disruptive to an R&D organization then it is the uncertainty and demoralization that occurs with a major downsizing. Every time management goes out and streamlines the pipeline — a buzzword for eliminating projects — they are not enhancing R&D productivity but decreasing it in my view. Fortunately, because we have exhibited constant growth since then, we have had a lot of continuity and much more momentum in the intellectual property (IP) arena than many of the companies that have gone through multiple rounds of M&A activity. Scientists are very proud people who want to do their research. But they are susceptible to emotional stress. They are not hard-nosed sales and marketing folks. They need to have a lot of freedom to get on with their job without too much management interference and without too much of the turmoil that comes with disrupting an organization through multiple reorganizations or layoffs.
I probably made an awful lot of mistakes, but also learned a lot.
Another industry-wide trend has been the increased investment into R&D in Asia. You were one of the early companies to test these waters. What you have you learned from this experiment? When we inaugurated an R&D laboratory in Beijing in 1997, we didn’t quite know how to start so we initiated a high-throughput testing project of Chinese herbal medicines to try to identify molecules that we could use to treat diabetes. We did identify quite a few active molecules, but they always turned out to be a known class of agents that was in the pipeline or on the market. This taught us, though, that our Chinese scientists were extremely dedicated. I realized then that they needed to do something else, so we focused them on optimizing our protein production strains. I wanted them to work on something a little precompetitive. We didn’t have them designing new insulin or protein analogues, because we tend to keep those to ourselves in the headquarter-based research laboratories. At that time in China, we were never quite sure about how IP and ideas would disseminate. Since then, as the IP concerns have become slightly less controversial, we have started to give them more research project leadership responsibilities, and they are running a range of exciting projects in collaboration with research laboratories in Denmark and the United States.
NATURE REVIEWS | DRUG DISCOVERY © 2014 Macmillan Publishers Limited. All rights reserved
