Novo Nordisk: Uli Stilz

“As scientists, we can make a real impact. I wouldn't want to do anything else with my life.”

No one would expect a large pharmaceutical company—with a history longer than that of the helicopter, parking meter, or electric guitar—to be on the frontiers of biotech. Uli Stilz, Head of Novo Nordisk’s Bio Innovation Hub, is challenging this assumption.

Uli’s story starts in the lab. He earned his Ph.D. from the Max Planck Institute and completed a post-doctoral fellowship at Caltech. However, after seeing firsthand the impact disease can have on families, Uli’s personal mission changed. He joined what would become Sanofi, to learn the art of discovering and developing new medicines.

Uli’s journey led him to Novo Nordisk where he currently leads the Bio Innovation Hub (BIH). His goal is clear: identify and grow new modalities and biology to treat, cure, and prevent cardiometabolic disease. The Bio Innovation Hub has already etched partnerships with the Broad Institute, Flagship Pioneering, and several emerging biotechs.

In his interview, Uli describes his career as one of constant learning—a requisite skill if one hopes to identify novel solutions to the most challenging questions in biology. Although the promise of GLP-1 agonists has shifted the paradigm of treating cardiometabolic disease, there is still work to be done. Recently, Novo Nordisk and a German biotech company called Evotec, announced a partnership to accelerate translation of work from the laboratory. Dubbed “LAB eN²”, they hope to increase the number of promising drugs moving from bench to bedside. Participating academic institutions include Harvard University, Yale University, Mass General Brigham, and Beth Israel Deaconess Medical Center.

Below is an interview with Dr. Uli Stilz, Head of Novo Nordisk Bio Innovation Hub:

---

1. When did you realize you were interested in science?

I was born in Southwest Germany, in a city called Mannheim, and grew up there for the first 18 years of my life until I finished high school. My interest in science began very early on, driven by a curiosity of the world around me. My family would do many hikes in the mountains. Observing all the plants and animals, I wanted to understand nature more.

At some point, probably between 10-12 years of age, I got a Christmas gift from my uncle, who was a physician. His gift to me was a microscope, and I started to dive a little bit deeper than what I could see with my eyes asking: “What do bacteria and plants look like under the microscope?”

The first thing I ever visualized was some algae. That was fascinating because it's so different than when you see a little bit of algae floating in the water. It is just some turbidity. And then all of a sudden, under the microscope, you see it in a completely different dimension. You realize there are some fine microstructures you cannot see with your eyes. That sparked my interest in science. Then, as is with any microscope, it turned out I needed a few chemicals, some dyes, and so on. This put me into an experimental mode as I looked to see how I could actually get more information from my samples. Because of this, I started to become more interested on the chemical side, seeing what these substances were doing. While this was happening, I was also curious about things like building rockets and those kinds of activities. These interests pushed me even closer to chemistry as a teenager. After high school, I started  my journey to become a scientist and study chemistry.

2. When did you first make your way over to the U.S. (and Caltech)?

I felt like my life was pivoting between different disciplines. As a child, I started in biology and then switched to chemistry. Going into my undergraduate, I started in Freiburg for two years and then went to ETH Zurich, the preeminent school in Europe for chemistry at the time. It was the heyday of vitamin B12 synthesis, the most complex synthesis which had been undertaken between ETH and Harvard. I really understood mathematics, physics, quantum mechanics, and how to make molecules. During the mid-80s, chemistry was very separate from biology and medicine, a discipline in itself.

After I had my master’s degree, I felt I knew so much about chemistry, but I didn't know anything about biology. There were some family events concurrently that highlighted to me, in a very personal way, how disease could impact life. These experiences inspired me to learn about biology and disease. But the question for me was, as a trained chemist, how would I do this?

I ended up interviewing at a few different places for graduate school. Something that I believe shaped my life in so many ways was an interview with a faculty member, Dieter Oesterhelt, at the Max Planck Institute in Munich. He had a 45-minute interview with me, but I think it only took him about two minutes to find out that I knew nothing about biology or molecular biology. The remarkable thing was that this did not matter to him. He wanted to foster young talent. He ultimately said I could join his group and do my Ph.D. with him.

As I started, I believe he created a little barrier or test to see whether I had the energy for joining his lab. He said he didn’t have funding for me so I would need to find my own. So, I went out to get a fellowship and then was admitted with him.

It was a fascinating time because Dieter Oesterhelt had discovered bacteriorhodopsin: a light driven proton pump. At the time it was really debated if this was actually a light driven proton pump. However, it opened the field of membrane biochemistry. In this research group I learned a few really key principles. First is the importance of curiosity. Second, I began to build the skills that allowed me to work between disciplines: at the time a mix of molecular biology, cell biology, and biophysics.

Later during my training, two really important areas of research opened up. The first area was bacteriorhodopsin, other members of the group discovered more family members like channelrhodopsin. This led to a serendipitous 30+ year journey in the field of optogenetics. This feat was awarded the Lasker prize in ‘21, which Dieter Oesterhelt received with his former student Peter Hegemann, and Karl Deisseroth at Stanford. The second was that one of Dieter’s students would crystallize a membrane protein for the first time. This won a Nobel Prize shortly after, but it opened this new field of understanding membrane proteins.

As a scientist during this time, these discoveries taught me to be curious and I really learned to appreciate the idea that breakthroughs often happen at the interfaces of disciplines. At the end of grad school, I had the thoughts: “What should I be doing? Should I go to academia or industry?” Academia was the frequent path for a scientist coming from a Max Planck-type institute. Or perhaps I should go to do more applied research in industry? I didn't know. To defer the decision, I pursued a postdoc at Caltech. It was a safe place between biology and chemistry working on a new modality at the time. There [at Caltech], we were asking ourselves, “Could we selectively recognize DNA with a molecular probe?” If you could recognize 14 segments of the alphabet in a DNA, then that would occur only once in the genome, and you would have a probe you could use to selectively turn a gene off or on. If you think about it in the context of the early 1990s, it was a very visionary undertaking. Its impact was fully realized later on with the discovery of CRISPR-Cas9 [and guide RNAs], but even at the time it was a really fascinating area.

During that time, I was reflecting and realized that I actually wanted to go into industrial research and contribute to finding new medicines. After my postdoc, I decided to go back to Europe and join a pharma company based in Frankfurt.

3.  Was there a culture shock coming to the U.S. as a German scientist?

I think there were a number of different factors at play. I came with both a chemistry and biology background and entered a very interdisciplinary research group at Caltech. That biologists and chemists worked together was totally new to me. In Europe, I saw the chemistry department and I saw the biology department, but I didn't see them so closely intertwined.

In the U.S., Stuart Schreiber, Peter Dervan, and later his student Peter Schultz pioneered this field of chemical biology. This opened the field towards studying biological questions from a chemistry lens. Later on, this became really fruitful in terms of crossing boundaries and helping support many unique discoveries. I felt that at the time, this was a very highly energized environment with very driven people. In these elite schools in the U.S., it’s a very driven group who are passionate about what they do. During this time as a postdoc, we had Lee (Leeroy) Hood on the same floor. Lee would stay in the lab every day until two or three in the morning. Sometimes around midnight we would have the best discussions and basically get to hear what was on his mind. Hood had an amazing group of 100 postdocs working for him. This contributed to a really high energy, high intensity environment.

4.  How did you get your start in industry and how did you make that transition?

I came back in 1992 and I interviewed with Swiss companies at the time like Ciba-Geigy and Sandoz. This was before their merger to become Novartis. I ended up joining Hoechst AG in Frankfurt because I liked the topic and the people. I felt that it was a good atmosphere. I must also add that I was naive. I was academically trained and had no sense for applied research and what it would entail. I was lucky enough that I worked with a group of good mentors and was given an important and exciting topic working on cell adhesion receptors. The very first project was in thrombosis. After nine months, from my lab, emerged a molecule which made it all the way to the clinic. I moved through the clinic with this molecule guiding its development, and I learned many things about what it takes to think about a clinical development plan and some practical questions like, “Does this molecule crystallize?” Initially, you know, I asked why is this even an important question. Thankfully some very experienced participants told me if it doesn't crystallize, it gets hard to get high purity levels, which poses a development challenge. It may also come in different polymorphs. Sure enough, that's what happened. It didn't crystallize. [The molecule] came in different forms which couldn't be produced because the different polymorphs had different properties. I learned all of these aspects: from how the molecule is designed to how the biology is explored, and ultimately how to progress to human testing. I was very fortunate to have the opportunity over the first four years of my industrial life to work on four or five projects in thrombosis, inflammation, and cancer and take a number of molecules toward the clinic.

That's how I found my footing--by having mentors and working in a very interdisciplinary environment with people who were willing to teach me.

5.  How did your skill sets evolve as you moved from your role as a scientist to that of a manager and how did your relationship with the underlying science change from there?

That's a really important question. I mentioned that I was lucky that I was given the opportunity to work on these important projects as a young scientist. After four years, because I was very productive, I was deemed to be suitable for a managerial role. In ‘96, I was promoted to my first managerial role and all of a sudden was moved from a lab with four technicians/lab techs to a group of 60 people reporting to me. And of this entire group, I was one of the youngest. I felt like I had to do a really good job. I had to be on top of everything and know what was going on in the different labs. I worked hard day and night to understand and support my scientists. After the first year in this managerial role, there was a round of feedback. Sure enough, it surfaced that some of my team members felt that I was a micromanager.

I came to realize that my job description had really changed. It wasn't about being successful myself. Instead, it was about making others successful. I think that's a really important transition point in a leadership role, realizing that it's very different. The success metrics are different. It is about helping others succeed and nurturing and developing talent. I learned this early on and became quite deliberate about it, working to empower and giving over autonomy and authority. The second lesson is that as a leader, you have to develop a vision people can get behind.

This needs to be a vision of the future that is enticing and energizing. This is an important leadership task, even if you don’t always exactly know things will pan out. In R&D, you almost never know how things will pan out. Regardless, you get to a point where you have a north star pointing you where you want to go and some key parameters which most likely will always be true. For example, I didn’t know that in 2000 what impact computational chemistry would have on drug discovery. However, I was certain investing into building a computational chemistry department was worth exploring. This was important for me to realize as a leader: you have to have vision, a north star, and a few key goal posts that everybody can rally behind.

I would also add a lesson in cultural awareness. I started in a German environment where I knew the culture, and over time, moved into a global leadership role. I was responsible for colleagues in Frankfurt, Paris, Toulouse, and New York. I started to realize that certain things which came from my cultural assumptions did not work well in other cultures with different expectations. For example, the things I tried to train myself in a German culture to become empowering did not work in a French culture. In French working culture, there's an expectation that managers manage to a higher degree and are informed about all details. When working globally it requires situational leadership and different cultures require different leadership styles.

[On how the relationship with the science changed moving up the managerial ladder]

Science becomes more conceptual. Today, if I had to take a flask and do an experiment, I probably would have a little bit of a learning curve to be productive.

However, over time, I accumulated a very broad overview and a good feeling for what is achievable. I also developed a deep optimism that, whenever I try something, something productive emerged. It’s not always immediately clear how to shape it, but entering a new field and experimenting, every time something productive emerged.

6. With regards to the Novo Nordisk Bio Innovation Hub, why do you believe you specifically were called to lead this initiative?

In many ways my life journey brought me between managing technology functions and managing franchises, like the diabetes innovation unit at Sanofi. I started on a 10-year journey revolving around innovation in ecosystems and how to innovate with biotech and academia. Along this journey, I accumulated a broad set of expertise in how to build a unit like this. I joined Novo Nordisk in 2014 and helped build strategic partnerships between 2014 and 2018. The question ultimately became, how do we further expand our innovation ecosystem? We have internal research and this was already being complemented with business development activities like acquisitions of existing technology or companies. Integrating strategic thinking we asked: would this be enough, especially in the cardiometabolic field, where historically there hasn’t been as much investment in the space and so there’s a smaller existing industry pipeline. The science is not fully understood and complex, requiring long clinical trials to get to proof points.

It was not enough to just buy what others have invented, we had to nurture it. This is something that the biotech environment is not fully enabled to do alone. Out of this discussion, an idea was posed asking if we should we do something in Boston. My manager at the time, Mark Schindler, looked into it and after some consideration, gave the go ahead.  

I didn’t know what we would be doing exactly, other than immersing ourselves in this highly creative, entrepreneurial environment. We knew there would be possibilities to drive innovation in unique ways. Over a period of 12 months since the inception of the idea, the Bio Innovation Hub started to crystallize and became a truly interdisciplinary team. Going back to my life experience over the preceding 20 –30-year period, productivity comes in the interface between disciplines. We built this unit around a triad between physicians, biologists and, in the broadest sense, molecular scientists. We think about how a system can be perturbed to bring it back closer to normal. Around this triad we built an interdisciplinary team here in Cambridge, deeply enabled with insight into disease, particularly obesity, diabetes, and cardiovascular disease because that's our main focus. It was also important that we built the team to be deeply connected to the rest of the Novo Nordisk R&D organization. In addition to bringing on several local scientists, we brought a few scientists from Denmark to Cambridge and have a deep connectivity to the broader organization. Then we looked for biotech companies developing new platforms asking the question, “If you build a new platform with new capabilities, how could this new capability actually be used to address unmet medical needs or unlock disease biology in a novel, unique way?” Ultimately, the goal is to co-create new product concepts which we can support, fund, and bring all the way to clinical testing.

The development of all this was by no means a stepwise process. It was also inspired by local Cambridge peers. We hosted a panel in Cambridge back in 2019 with a few biotech CEOs and academic researchers, like Bob Langer, some venture capitalists and asked the group a few questions. One question was is it too late? Everybody's already here. The answer was, No, it's never too late. Science keeps accelerating and at some point, you just have to jump on the train. We also wanted to build something fairly nimble so that we actually talk to the environment around us and not just to ourselves. We wanted to keep a small unit and talk to everybody else around us.

7.  How do you think about risk when working with small biotech companies since large pharma companies usually purchase later stage biotechs to maximize the probability of success?

My take on this has been that acquisitions of late-stage assets is super important, but we also have to play a role in creating our own future and shaping the environment. For these complex cardiometabolic diseases, there is not enough happening spontaneously. The last MassBio report showed the investment level into the metabolic space was about 2% of the total venture investment. There is so much more happening in other areas, like oncology. To some extent, science has driven us to this because a genetically identifiable disease trait more easily aligns with a precision medicine approach.

However, hundreds of millions of people live with chronic cardiometabolic diseases and are in urgent need of new, improved treatments. There is huge medical need that is not being fully met, but we are committed to shaping the environment and driving our own future to bring new innovations to the people living with these conditions.

8. What does that partnership look like between the Bio Innovation Hub and its companies?

Every partnership has its own specifics and dynamics. There is not one single blueprint for every partnership. As an example, at the end of last year we signed an agreement with Dewpoint Therapeutics, a biotech which emerged out of a new insight in cell biology—that genes are regulated by transcriptional condensates. In diabetes over the last 100 years, we have found different ways to symptomatically treat and lower glucose but have not been able to unlock what is driving the disease process. People with diabetes who are being treated keep progressing. We found that this new paradigm in cell biology could be a clue. Thus, we started a research collaboration at the Whitehead with Rick Young, Phil Sharp, Rudolph Jaenisch, Linda Griffith, and others to study this phenomenon. We brought the diabetes expertise to this. This led to some discoveries and publications but has brought us to a point where it felt like there was a new paradigm that potentially could unlock diabetes. We started our collaboration with Dewpoint with the first phase uncovering new biology and then the second phase developing the new molecules for diabetes therapeutics.

It is all driven as a joint team. The scientists from Dewpoint working hand in hand with scientists from Novo Nordisk. We also have scientists from our Oxford group that are more the human genetics side and scientists from our diabetes therapy area in Copenhagen. It's a multi-site, multi-expertise effort. The Bio Innovation Hub was designed as a biotech within Novo Nordisk. This is actually really important because it was designed to be agile and connect to these entrepreneurial units in different ways. It's also designed with a ring-fence budget to manage the risk. From the corporate level it's clear what resources are actually committed to push the boundaries of science and innovation.

9. How do you think about which companies you partner with and what mental models do you use?

We systematically scan for emerging modalities and then connect it back to the question of what could potentially solve problems that cannot be answered with today’s tools.

My mental model for finding these technologies consists of a few questions. First, is a new model emerging that could solve for something previously solved but in a more elegant way? The term “more elegant” can mean something more convenient for people: enabling less frequent dosing for example. That would make a difference for patient compliance. The second question is one of sustainability. For example, if I need fewer doses, the amount of injection pens wasted will be much less. The third question is about affordability and scalability. Can we bring a medicine not only to 50 million people, but to 500 million people? That is what we are looking at in the bucket of known biology. Making improved medicines across those parameters.

Then there is this other question about unlocking disease. How can we understand the complexity of disease and find new intervention points that could help us slow down, stop or reverse disease progression? We have a really strong interest in this and it drove our partnership, which we recently announced, with the Broad Institute. This collaborative work is about getting to the cutting edge of biology and uncovering the complexity of disease to find disease modifying mechanisms.

10.  What’s next for you and Bio Innovation Hub? What should we be expecting in the future?

I haven't yet talked about our unique partnership with Flagship Pioneering, which we first started to think about in 2019. Imagine an innovator like Flagship working on next generation platforms, combined with a pharma company like Novo Nordisk that has 100 years of history in diabetes. These are two perpendicular innovation models. Our teams started conversations and had the insight to do something modular—because we wanted a partnership where we didn't know what we would invent, but where we could work at the intersection of science and business to drive innovation. Together with Paul Biondi and the Flagship team we created a unique partnership framework that we announced in 2022. We have some very exciting programs underway. I'm actually most excited about stuff where I don't know what will happen because there's so much potential to innovate in different ways. There is such a positive energy between our two organizations, and it forms the base of long-term partnership that can innovate in ways we can’t even begin to imagine now.

It is somewhat similar to our agreement with the Broad Institute. We're coming together with such an enlightened institution to help us uncover the complexities of disease. We are starting with three programs in diabetes and cardiac fibrosis with the potential to add more over time across different directions and dimensionalities. We really want to capture value out of the partnerships we currently have and continue to find new, exciting science. This goes back to my core belief in life: it's important to tackle real big problems, and I have a deep conviction that we will find something transformational.

11.  What advice would you leave for young Ph.D.s and students looking to make an impact on biotech?

Looking at my own life journey and career, I would tell people to be curious, entrepreneurial and confident. Make jumps in your life. Start to develop expertise in one area, but also feel comfortable to jump into adjacent disciplines. I would also advise to build a broader, wider insight into science and different ways to approach science. I jumped from chemistry to biology. Chemistry is all about structure. Biology is all about function. I learned about navigating in both dimensions. I think becoming multi-literate is really important for scientists.

I would also say explore different research groups in different places. I changed location every three to four years, going from Frankfurt to Zurich to Munich, to Pasadena. Over the course of 8-9 years, I was at four different institutions/universities. Every place has its own characteristics and I was so fortunate to meet so many fantastic people and mentors. At ETH, I remember Vladimir Prelog, the Nobel Prize winner was still going to the faculty seminars. He was approachable. You could discuss science with him and that was fantastic. I also had a wonderful Ph.D. supervisor. Look out for people who want to mentor you and look for people who give you opportunities.

For the more senior people reading this, give young people opportunities, even if you feel like their CV is not the “perfect fit.” Young scientists can learn new things quickly, and you need to trust that they can do well over time.

12.  Any last parting words you’d like to leave for readers?

I really enjoy this life. I think it's because I'm curious and excited about science and what we can do, more so than ever before in my life. As scientists, we can make a real impact.  I wouldn't want to do anything else with my life.