The scope of chemistry has increased dramatically

With all the talk about new therapeutic possibilities revolutionizing the pharmaceutical industry, chemistry, with its century-old tradition, is seemingly receding into the background as new technologies such as breakthrough gene and cell interventions trigger headlines and fan patient hopes. But nothing could be further from the truth, said Muneto Mogi, who has been heading the Global Discovery Chemistry efforts at Novartis since 2023. Emerging therapy platforms such as radioligand and RNA therapies, which have popped up on the scene during the last decade, are in fact helping chemistry expand rather than rendering it into a museal technology. “Our area of scope has increased dramatically,” Mogi said when we met him in Basel to discuss the future of scientific research at Novartis. “Traditionally, chemistry has been associated with small-molecule drug research. But new therapeutic areas such as radioligand and RNA therapies are broadening our field.”

Interview with Muneto Mogi

Muneto Mogi: "I love chemistry."

Chemistry has likewise made huge technological improvements, Mogi said, helping it become more efficient and environmentally friendly. Artificial intelligence, he adds, is also likely to play an increasingly bigger role in drug discovery. While it is unlikely to prove a magic wand, the technology will be used to help speed up development times. The excitement over this technological quantum leap was palpable in every one of Mogi’s words when he walked us through his career and told us the story that prompted him to pursue a professional path in science and medicine. His fascination with the pharmaceutical industry was triggered during his teenage years. “My father, who worked for the United Nations, was on an assignment in Somalia. He regularly took me to the refugee camps, where I could experience first-hand what it means to have or not have a medicine – be it aspirin or something else.” The experience stuck with Mogi: “I can still remember the faces of the patients and the families, their suffering and how their expression changed to a smile once they received their medicines.” In this scene Mogi also made a crucial observation, which would influence his later work. “A medicine would not only help the individual but the entire community. This struck me deeply. While I wasn’t sure what career I wanted, I always had in mind that I would do something with medicine.” After completing his high-school education, Mogi opted to study chemistry. But it was not because he discarded medicine. To the contrary, he chose chemistry because he realized that – more than just treating patients – he wanted to create new medicines to help “bring a smile to patients’ faces,” reviving the experience he had at the refugee camps he visited with his father. “I did consider going to medical school,” Mogi said. “But the reason I didn’t was connected to my childhood experience. There are many doctors, but without medicines, their contribution will be limited. So, I really felt that I could touch more people and have an impact on society if I worked on the development of new drugs.” After his studies at Kyoto Pharmaceutical University and the University of Boston, Mogi joined the pharmaceutical industry, first at Bayer, then at Shionogi, before joining Novartis in 2005, where he worked in various roles in medicinal chemistry before taking over the entire unit last year. During all this time, Mogi’s outlook on his work has never changed. “From the very beginning when I joined the industry, I have only had one dream, which I still have today: to get at least one drug to patients.” There is a good chance of this happening soon, as he was instrumental in the development of a compound that has recently reached late-stage development. In his new role, he is also likely to oversee the development of many more medicines in the years ahead, helping him realize his childhood dream and living up to the Novartis mission to improve and extend peoples’ lives.

Mr. Mogi, the word chemistry often triggers negative associations such as toxicity or pollution. Pharmaceutical companies also seem to be moving into other fields. Is this the beginning of the end of chemistry in medicine? No, definitely not. Though chemistry is the oldest technology used in the pharmaceutical sector, it has evolved substantially over the past few decades and is also crucial for the development of emerging technologies such as RNA and radioligand therapies. Furthermore, we have huge experience in the field, which by its nature has an almost unlimited potential given the inherent ability to create new molecular combinations. Can you talk a bit about the most recent technological developments? One important aspect is that today we are working in a completely different environment. For example, the scale at which we do chemical synthesis is much smaller that it was in the past. Today, we can execute tests with a few droplets, helping to increase efficiency and reducing our environmental footprint. We are not using old-fashioned solvents anymore and are working towards creating a sustainable and green chemistry. Another important aspect is the level of automation, which allows us to work faster and be more precise. In which areas are you pushing to increase automation? One important area is our compound library, which contains millions of small molecules, which we traditionally test in classic high-throughput screenings. As part of this, we use robots, which help us select and put the compounds into special plates where they are tested against biological targets. We have continually improved this process over the years. We have also created so-called DNA-encoded libraries, which are revolutionizing drug discovery. Can you talk more about DNA-encoded libraries? DNA-encoded libraries contain combinatory chemical building blocks that are tagged with a strand of DNA. This gives essentially a DNA barcode, which allows us to identify them easily. Since we are using chemical building blocks to create new chemical combinations – rather than just full compounds – we can literally prepare hundreds of millions of new molecules in a week and test them in a single vial against a biological target. To see whether a compound is reacting with a target, we simply wash out the vial. Thus, we are not only more efficient, but can also zero in on more difficult targets by identifying various binding sites. How do you drive this kind of technical evolution? We collaborate with academia and other institutions to stay abreast of technological developments. Likewise, emerging technologies such as radioligand therapy and RNA-based treatments offer new possibilities in the realm of chemistry, where we are working with leaders across the globe. We also have top talents across the world who are passionate about innovation and are continuously evolving to improve the ways we do drug discovery. How are you leveraging chemistry in the nuclear medicine and RNA space? While RNA-based therapies are not classical small-molecule drugs, the creation of synthetic RNA requires deep chemistry expertise. Likewise, in the space of nuclear medicine, small-molecule ligands are an alternative to antibodies or large peptides for transporting radioactive particles to tumors. Using antibodies or peptides can create challenges when these ligands are excreted through the kidneys. Small-molecule ligands can offer a solution. What are other advantages of small-molecule compounds? Small-molecule compounds play an important role in treating chronic diseases such as cardiovascular conditions, in which patients prefer oral therapies. Because of their size and ability to cross the blood-brain barrier, small-molecule compounds are also an important option in the neuroscience space, to name another example. This shows that these compounds remain essential to the pharmaceutical industry. How is artificial intelligence playing into these developments? We are using machine learning in drug design as well as synthesis design. And by doing this, not only can we increase the speed with which we pursue our projects – more importantly, I’m very, very confident that this will increase our probability of success. We are working with Microsoft in this space. While we are still at the beginning, we expect that with the continual refinement of our algorithms, we can achieve major breakthroughs. We are already seeing huge gains in efficiency today. What is your vision regarding the use of artificial intelligence? The long-term vision is that artificial intelligence could provide a molecule that would essentially be developed into a drug. This ideal may be too hard to achieve, even in the long term. But in the short term, we can really leverage the technology to aim for a significant impact. Where do you see this happening? In typical medicinal chemistry projects, we make and test an average of 4000 compounds per project. I believe that artificial intelligence would really help us speed things up. Are there other cases for the use of artificial intelligence? I also believe that artificial intelligence can help us create better molecules with increased probability of success. Today, projects are often stopped due to toxicity issues. Artificial intelligence can help here. Even before the rise of artificial intelligence, we had been able to improve our predictive models in the realm of pharmacokinetics. This gives me ample confidence that we can achieve the same with artificial intelligence when tackling toxicity. You have been with the company for almost 20 years. What makes Novartis such an interesting employer for you? Novartis is unique in the sense that we have such huge diversity in terms of skills and technologies. Our colleagues come from all corners of the world and excel in different scientific areas. Furthermore, collaboration between the different functions is also very strong, which has been enhanced through our new governance model in which discovery, development and commercial teams work together much more closely from the beginning of a project. Why is this collaboration so important? We cannot do chemistry alone. It’s always connected with other departments. I think this is really the reason I joined Novartis – this sort of enormous diversity we have in the organization as well as the collaborative culture to bring these different disciplines together. Looking back at your long career as well as looking to your childhood dream, are you happy with how things have evolved? When you see how patients regain their sense of independence when they receive the treatment they need, there is not much else that gives you this kind of satisfaction. Being able to help an entire population with a new treatment option has always been my dream since I was a student. Being able to work in a world-class company such as Novartis not only makes me proud on a personal level but gives me this deep satisfaction that I can contribute to a bigger societal goal together with our colleagues who share the same passion and vision.