"I will always ask myself, what can I do with my knowledge in science to be able to bridge that to patients?" - Michel Detheux, co-founder and CEO of iTeos Therapeutics
"I will always ask myself, what can I do with my knowledge in science to be able to bridge that to patients?" - Michel Detheux, co-founder and CEO of iTeos Therapeutics
I will always ask myself, what can I do with my knowledge in science to be able to bridge that to patients?
John Simboli:That's the voice of Michel Detheux, co-founder and CEO of iTeos therapeutics. L isten in now to hear my conversation with Michel at the U.S. headquarters in Cambridge, Massachusetts. I'm John Simboli. You're listening to BioBoss. This afternoon I'm in Cambridge with Michel Detheux, co-founder and CEO of iTeos Therapeutics. Michel, welcome to BioBoss.
Michel Detheux:Thank you very much.
John Simboli:Michel, how'd you find yourself as co-founder and CEO at iTeos?
Michel Detheux:I would say that the story started more than 25 years ago. During my PhD, I was passionate about discovery and I found that I would be impactful if I can be in the driver's seat and develop a company for an important disease. And it took me more than 15 years to find the right science, the right partner, to start the project. And iTeos Therapeutics started in 2012.
John Simboli:And is that a decision made easily because it's clear? Or is that a decision, to make that change, that's difficult because it's hard.
Michel Detheux:It's hard, every day. But it's also what makes it impassioned. My wife told me, if it will not be hard you will never do it. And in fact I was approached by one of the directors of Ludwig Cancer Research, one of the top research Institutes in the U.S., to start this company. He gave me a call and told me, Michel, I have some data that could be the starting point for a company. Would you be interested? It took me two seconds to say yes.
John Simboli:Was there any process at that point of thinking, maybe I need to do my due diligence. I'll sift through and look at a lot of similar kinds of companies and maybe it already exists. Maybe I can build what's already there versus, no, I think I need to start something.
Michel Detheux:I was convinced that I could start as soon as I found the right science. And the Ludwig has some of the best science in the world, Then the decision, I was happy to take and I did not make a due diligence to wonder if a competitor would be more advanced or well-funded and it would be difficult. I believe that cancer is still targeting one man out of three, one woman out of four, today, will increase in the coming decade. And then it's a big commitment.
John Simboli:Can you say from your memory, can you say what your picture of what it would be like to be the co- founder and CEO, what you thought it might be like? And then, in reality, here at this point, sitting at this table here in Cambridge, what it is like?
Michel Detheux:First, co-founder? What's the difference with founder? You have two people who need to align. And it's an interesting story because rapidly it appeared that the science could be more important. And I like to use the image, and I explained, look, it's like a mother and a father raising a child. I will be the mother for the project and I'm going to deliver the project and I'm going to take care of the project every day after. And it's what I've done well. I Would say that I would never have imagined that seven years after, I would be in Cambridge managing a company of 45 people, s pl it on eac h si de of the big water. But this is something which is in teresting and yes, I still love, like the first day, what we are doing. Especially now that we are treating patients and you st art to see impact on patients and the life of the people on a daily basis.
John Simboli:As you work day-to-day to make sure everything is going absolutely right and the execution is flawless, do you still, in this cycle, do you still have time to think—I wonder what will happen, what good I can do in the world, if this project succeeds the way I hope it will?
Michel Detheux:Yes, indeed. This is a driver on a daily basis. During a downside or times when it's more difficult, we keep thinking that if we succeed, we'll cure people who are like us, father, mother. It's really something which is motivating. And it's something which is always included in our activities. I believe that I split my time 50% managing the company, 50% with external stakeholders. The contact with external stakeholders always puts you back to the fundamentals and long term. What do you plan to do? Or can you differentiate? And what are your plans in three years?
John Simboli:In this process, have you found that you have a management style that is you, that works for you, that is different from others?
Michel Detheux:I believe so. I believe that each CEO is different. I like the "P's"— passion, patience and persistence. To think about cancer patients in our care. It's not some one patient. I mean it's really hard for me to take the time or try to take the time to get things done. I'm passionate. I believe I'm also very transparent and, well, being Belgian, with a big quality—humility. And humility is not weakness. And I see that even more since I'm here in the U.S. The style is very different but can be very complementary.
John Simboli:Can you recall at age eight or nine or 10, a young man, young boy thinking "I want to grow up to be this" and having a picture of it?
Michel Detheux:I did not, at eight and nine, say, I will do that. I believe that people who are going to do really great things know in advance that they want to do something. I have one of my daughters, who told me at 10, I want to be a lawyer and she's now ready to be a lawyer. I started my university studies as a bio-chemical engineer or bio-engineer and when I started, I fell in love with chemistry. Second year I fell in love with bio-chemistry and from that I understood that I want to understand how our body works and if one day I can cure patients. And it was a starting, but that was 19, not nine.
John Simboli:That's sort of a magical thing when you find what you're in love with. But can you say what it was about biochemistry that made you say that "I love this?"
Michel Detheux:Because I thought that we are so complex and being able to understand how our body works and what we do with the food we take in every day to become human beings. Being able to interact, take care of others and do great things, do sometimes crazy things, but be able to move forward and build a world just from the basic chemistry that was present 4 billion years ago in just the water is something wonderful.
John Simboli:It sounds like it's a thing, a beautiful thing, as well as a precise thing in the way you see it.
Michel Detheux:Yes. And I believe that I really am a scientist all my life. I don't believe in "mad scientist." There are some, and there are some very good ones, under the "mad scientist." I'm not going to write a paper at 2:00 in the morning , but I will always ask myself, "What can I do with my knowledge in science to be able to bridge that to patients?" And I believe that where I'm strong is to make a bridge between science and business and operations. I'm not the best at anything. I'm interacting every day with people more expert than I am—my chief medical officer, my chief business officer, my scientists. But I believe I'm able to make the bridge and show the direction. I'm a starter. Then my role is to take the team, manage the risk and move forward and find solutions. I'm also a fixer when we have an issue or need to solve that. This is my role.
John Simboli:When people say, what do you do for a living, what do you say?
Michel Detheux:I would say that, indeed, a CEO must plan for success and be ready for the worst. And this is our daily job. I mean last year when we completed the $75 million round B, it was a true performance of the team. At the same time, the day after, it was already necessary to think about the next step and the next funding stage, Then you must be able to jump from the daily activities—what do we do today? Or do we connect the team to align the team about where we go? At the same time you have to wonder, what am I going to do to be funded in two years and be able to continue to develop the company. When I speak with the team, I tell them we are in the boat , we are rowing in the boat. I like to share information to be sure that you know where we are and where we go. And the journey is never a direct journey. You have plenty of adaptation, adjustment that can seem chaotic. At the same time, if you know where you want to go, you can keep the direction and continue to move forward. You must be adaptive. You must be pragmatic, but you have direction.
John Simboli:To my English speaker's ear, iTeos sounds like an unusual name to choose for a company. Does it have a meaning?
Michel Detheux:When you create a company you have to do big things and small things. Finding them, finding your logo is one of the most important small things that you have to complete. iT means immunotherapy, I mean learning or predicating the immune system to recognize and attack the tumor. And the Eos is the goddess of the sunrise.
John Simboli:When people say , "Who is iTeos," what do you like to say?
Michel Detheux:I like to say that it's a drug discovery company developing new treatment for people living with cancer. I mean, again, cancer is something that everywhere is close by for multiple reasons. And you don't need to speak too much—when people are not aware of the time it takes to go from a concept to a drug on the market, and you have to explain. But it's not complicated to understand that you still need new drugs because every day people are dying from cancer despite all the treatments available on the market.
John Simboli:When people who are important to you, to understand who iTeos is—whether they're investors, whether they're potential partners, employees, could be a very broad range of people—when you describe to them who iTeos is ,what iTeos is, and afterwards you test to see and maybe after a very compressed 15 minute presentation, did they understand? Sometimes they will, sometimes they won't. When they don't, what is the misunderstanding about iTeos? How do you help them say, "No, no, it's actually this?"
Michel Detheux:They don't often realize the risk management. To take an example. a few years ago I discussed with CEOs of several of the biggest companies in Belgium, but classical industry. And they were expecting to meet with a "mad scientist" doing strange things in the lab. And finally they exited the room by telling me, "It's crazy how you must manage the risk because in our classical industry, we do a plan for five years. We execute the plan. We could miss our target, but the plan is set up for five years." In a biotech company, your plan can change several times a year. Sometimes every month when you are into a more challenging period. Then I believe that people can easily understand why you do drug discovery for cancer. Sometimes it could be a challenge to explain that we are science-driven. I mean many companies have a specific platform. They develop a specific technical approach. We don't do that. We are driven by science. We are mode agnostic. We are focused . I mean we are working on, specifically, immunooncology. I got in the past, and even recently, I often get feedback of "Should we be open to other diseases or should we be broader?" I believe it's important to be focused, to be on the point. I like to compare what you are doing to sport; we are like a basketball team and we need to be all together on the ground to win the game.
John Simboli:When you get into the question of specific cancers and specific ways that you're thinking about immunooncology, do people grasp your approach? And if they don't, what do they misunderstand about the approach?
Michel Detheux:Yes. This is a very good question and this is important. While one of the challenges is to realize that when you are still in the early stage clinical trials, you haven't yet selected the indication that will give you approval in three to five years. And you are still exploring different options. Obviously, you have a scientific rationale, you have a clinical rationale. You have the competitive landscape. And for the moment we have one program at the end of phase one. Next month we still have probably a list of 10 to 15 indications and sometimes people feel that we should be already well-defined in terms of which indication we want to go first. When we speak about a given cancer, lung cancer for example, which is one of the major ones, there are multiple subtypes. Second, there are multiple treatments and the treatments which are approved today could be different from the treatment in three years. Then in addition to managing the challenge of your own program , you have to understand how to position in the market to be sure that when you arrive on the market you are not outdated compared to the progress of the competition. That is one of the misunderstandings. Today we are not focused on one specific cancer. We are still working on several options, you know, to build options. So, recently an investor asked. "Can you define the market for bladder cancer?" And we did the exercise because I had the chance to get the team, with people who are experienced, my CMO was head of oncology at Sanofi. My COO/CBO was CBO at Endocyte, the company which went very close to public, to market launch, and finally was acquired by Novartis for more than $2 billion last year. I have the experts who can answer the questions and be sure that we are at the same level as the expectation of investor. But at the same time you must keep your flexibility. And even if you believe that one indication could be the best one, you still have some data that could show you that the number two, number three, option finally becomes the number one for multiple reasons. And we must remain agile in what we are doing to be sure that during the development, even if we have a master plan, we can adapt our strategy to deliver the best drug to the best patient population. And you have some investors or some stakeholders that would be interested in two late-stage clinical development companies who know exactly in which indication they are with the time to the market. That could be one or two years where the competitive landscape is well understood. Again, we are preparing the best case scenario, three to five years to market approval. What if you take 2019, compared to 2014, there was tremendous progress in the way to treat patients. And even if some guru can predict some of them, there are still many options to build.
John Simboli:Michel, what's new at iTeos Therapeutics?
Michel Detheux:What is new? I would say in 2019 we became a clinical stage company. I know that for the external world, it doesn't mean a lot. For the team and the 45 people working at iTeos, you're already starting to treat patients and all what you have done during the years where you were at the research stage or preclinical stage where you work with different models, but you are not yet with the humans. Today we have treated a significant number of patients. This year we have learned a lot from these treatments. We're starting to see some impact on the patients. And not only have we been about to start the first program this year, our lead asset, the A2A antagonist program, but we are starting a second program in the coming weeks. Then in the last 12 months we've been able to put two programs in clinics, which is a big achievement for a company of 45 people.
John Simboli:What makes iTeos Therapeutics different from other biopharma companies or peer companies in the immunooncology space?
Michel Detheux:I would say that our difference is based on our pipeline, the science that we have developed to differentiate our assets compared to competitors and what we plan to do in the future. But we are still building our difference every day and our difference would be confirmed if one day we've reached the market and are able to cure patients.
John Simboli:What kind of partners are a good fit to iTeos?
Michel Detheux:If iTeos is, one day, successful for patients, it would be due to the stakeholders and the partners. Then, indeed, iTeos is a good example of a company with experience and leverage with different type of partners. We are a spinoff o ff of Ludwig Cancer Research, which is, again, one of the top t hree research Institutes in the U.S. We are the first spinoff of t h e L udwiig that they have directly funded in cash on top of the technology cancer. Two years after we started, we were a six person company. We did a deal with Pfizer at that time. That was number one in t he world. It was a tr ansformative d eal for iTeos and allowed me to grow the company from six to 42 people in 15 months, build the pipeline and differentiate ideas. Last year when we were ab le t o attract MP M, one of the key investor VCs in the U.S., it was another important move compared to the previous stage of the company. And attracting people who will do the job every day. At the lowest position in t h e c ompany, the junior associate to the highest one, like our CMO and COO and CBO who joined this year, will allow us to build on our success towards curing patients with cancer.
John Simboli:So as a company that's in Belgium and in Cambridge and touching people all around the world, is it possible to talk about a culture? What would be the culture at iTeos?
Michel Detheux:Science-driven and, again, patient. I mean, I love to say to the people that I'm hiring—and I hire most of the people in the company, not anymore the junior ones in Belgium but all the important functions—I want to attract you and let you grow with the company and build success together. Again, I like the analogy of the basketball team: one player can win a game but we'd never win the championship. Then, as a team, being complementar,y that we can make the difference. And I want to get people who are passionate about what they are doing. And we can get up and down, but people believe that we are shaping something together.
John Simboli:What can you tell me about the pipeline and how it helps to differentiate who iTeos is?
Michel Detheux:When we speak about cancer, there are lots of different diseases. And you have three stages in this cancer development. The first step is elimination. You, I, everyone in good health—immunocancer cells, they save our life. The second stage is equilibrium. Some cancer cells can stay forever in your body after mutation and will not become a tumor. The third stage is escaping. These cells, after additional mutation, become crazy and develop like hell and give the disease. We must realize that both in terms of a type of cancer, but also the mechanism that they use to escape, that there are multiple mechanisms. We have decided to focus on two major mechanisms in what we call the tumor microenvironment, where the cancer grows. One is what we call immunometabolism. These cancer cells can use very nasty ways to escape the immune system either by preventing the immune system to be active , or by hiding from the immune system and be invisible, or by poisoning the immune cells and preventing immune cells to be active. Then we have decided to focus on two main pathways, immunometabolism, what metabolic change prevents the immune cells from being active. And cancer cells also devoid immune cells , which are known to be immunosuppressive, to be sure that these immune cells which are devoid by the cancer cells can build a wall that will prevent the normal immune cells from attacking the cancer. And we are targeting that, too. Just as a brief example, when we started, we started on an enzyme called IDO1—that was just after we started. This mechanism has been used f orever by pregnant women to protect the fetus from the immune system. The fetus has 50% of antigens. It's a foreign b ody for the immune system but can develop like most of the pregnancies. And tumor cells hijack that enzyme, which is highly expressed in the placenta, to create this immunosuppression for the f etus. The tumor cells hijack t hat system to be invisible during the pregnancy. And you have multiple mechanisms like that. Our lead program today, an adenosine A2A receptor antagonist, is another mechanism which has been known for a decade where adenosine has played an important role, to be sure. Then when you have an immune response, inflammation in your body, you can control this inflammation to avoid any kind of autommune disease. And the tumor hijacks the system to develop an i mmunosuppressive mechanism based on t his adenosine pathway. And we have developed a tailored program, which is very w ell differentiated from our competitors, to develop a c ompound that could make a difference for that pathway and improve the treatment of multiple t ypes of cancer.
John Simboli:To what extent is the word microenvironment, that you just used, to what extent is that central to what it t is that iTeos is exploring?
Michel Detheux:This is very important. And when I told you that we were differentiated by science, all our people are working on three pillars—tumor immunology,, pharmacology in vivo, and consortium, medicine. All the other activities are outsourced to partners across the world. And the tumor microenvironment could be like probably the peak hour in New York where you can get a high level picture of even 1000 people in a small space. But what is the dynamics between the tumor cells, the immune cells, the endothelial cells and all the other cells around that, that we create a unique environment favoring the tumor growth? And having a better understanding of that is very important. It's what we did for the adenosine A2A antagonist. We have designed something that was very different based on our understanding of what is happening in the tumor microenvironment. The second program that will have in clinics next month it's an antibody. And there we compete with the biggest players—Genentech, Merck, BMS. But again, we have approached a differentiated strategy where you find Genenetech, BMS and Merck have a similar one. We still believe that we can compete with these giants by having a clinical strategy that will be different, take more risk. We have to take more risk.
John Simboli:When people ask you about the therapeutic areas that you're working in, how do you like to answer that?
Michel Detheux:We start with the basic cancer. Now you have hundreds of different cancers and even in a specific cancer you have specific subtypes ,. Today, with the fact that we are moving towards phase 1B, phase 2A, we really work on selecting specific indications and specific combinations. Then we really enter into the curve of our objectives and select the most relevant patient population to move forward and show that we are able to develop drugs that really improve their conditions. We believe that, interestingly, with immunocology you are not restricted to a type of cancer. I mean we have programs moving forward with solid tomors but we have also the same program that could be highly valuable for emetogenic cancer. Then I would say that today we have a very large menu of options and we have to select the options that would be the best , that would give the best benefit to the patients. This is our challenge. The challenge is not to be too much focused. The challenge is to select the best options among a very large bundle of possibilities. One of the differentiators of iTeos is the fact we are multi-modality agnostic. We have been able to build expertise to develop both small molecules and antibodies. We started with idea one. We have developed a best in class A2A antagonist and in 2020 TIGIT could appear to be a next generation PD1 that could make a difference.
John Simboli:How did iTeos decide to establish a presence in the U S, and why Cambridge?
Michel Detheux:When I was working on the next capital increase in 2016 and 2017, I had screened a very large mode. I've probably met more than 100 investors. And again, the U.S. is a leader in that field and I met many U.S. investors. As I told you, we did a deal with Pfizer in 2014. At the end of 2017, Pfizer decided to leave the program for strategic reasons. I always claimed that if they would do that it would be an opportunity for iTeos and, indeed, after we announced exactly two years ago, I got the attention of MPM , one of the lead investors in the U.S. , venture capital investor, and things moved very rapidly into their interest in iTeos. I believe that European companies develop science which is of similar quality to U.S. companies. They are also able to be very pragmatic. And finally , in terms of price to attract investors, European companies are less expensive.There is more and more attraction from U.S. investors. And when MPM came for the due diligence, one of the first questions was, "Are you ready to move to the U.S.?" And I knew it was a key question. And I said, yes. I believe that the U.S.is where the investors a re, including NASDAQ. The stakeholders like analyst experts, patient groups, have the most expert and the pharma biotech partners, even if they are European, will be based also in the U.S.
:Then the U.S. is the place to be. And then coming to the U.S. was something that was driven by the $75 million round B lead investor. Again, i t was an expectation from that s ide to see me moving here. Cambridge was my best choice. Even if t here a re o ther cities t hat could have been very good choices, but managing a company, with two sides distant from 5,620 kilometers is a daily challenge. And being in Boston, first, it's probably one of the most dense communities in biotech pharma. I was asked, "Why are you going to Boston?" A nd I did a comparison.There are two dozen pharma biotech companies in Europe, W estern E urope. There are 1600 companies in Massachusetts of similar size. When I was in Belgium, I was traveling one week every month in the U.S, with 5-10 meetings e very d ay.. Now I have the people visiting us in Cambridge. And there's a cost—it's clearly more expensive than you hope—but it's an opportunity also and i t's what we are building to keep the t wo l ocations and get the best of both w orlds
John Simboli:In each of those communities, in Belgium and here in Cambridge, which organizations do you find help you to get information out and to help you to take in what you need to know?
Michel Detheux:MassBio is one of the organizations which is useful. I would say that I also leverage the MPM network, which is tremendous. And this is really the five star network and being part of the MPM portfolio companies opens so many doors that I could not even dream of that before coming here.
John Simboli:I imagine being a CEO of a business can be rather isolating because your work is so intense. How do you maintain your communication?
Michel Detheux:This is the one of the other values to being here . I mean, I didn't mention, but it allows me to be connected to the best people that could help us to build the company. I had also been able to attract as a CMO, the previous head of clinical oncology at Sanofi and my CBO/COO Matt Call, is also very well connected in the U.S. I've worked with the stakeholders in the overall landscape. I mean, in the two past years I've probably met more than 100 investors in the U.S. I've built a relationship with many banks. And it's a snowball effect when you start to be visible. As visibility increases, you meet more and more people that you will be connected to. I mean, I would never be part of the club, if I can say that. I did not grow up here. I'm not connected like many people are. But at the same time, I believe that I can build the best of both worlds. I'm well connected in Belgium, even if my connections increase everyday. I forgot to mention that one of the big added values of Belgium also is being supported by institutions and government. We received more than $44 million dollars of grants from the Walloon region, the state where iTeos is based in Belgium. And I like this idea to keep the roots in Belgium, develop the tree in U.S., But build a connection on each side with my stakeholders.
John Simboli:But it's not just the CEO. My understanding is it's the people that you surround yourself with. Are they important to the success of the company?
Michel Detheux:It's what make iTeos different. Iteos is a team. We have a very good team with high expertise. I would say it's one of the differences with Boston. People are more experienced in biotech but they are less stable also. They change quite often at other companies. We have a quite stable team of 40 people who really want to make the company a success. And again, if, one day, the company is successful it would be the stakeholders, starting with the team. And from the most junior assistant to the highest expert in the company, these people are doing the job on a daily basis and I would be nowhere without that team supporting the development of the company to help patients with cancer.
John Simboli:Michel, thanks for spending time with me and talking with me today.
Michel Detheux:It was really a pleasure. Thank you John.
John Simboli:Michel 's approach to leadership begins with a fascination with biochemistry and insistence that his scientific knowledge will benefit patients. But he takes care to avoid a "smartest guy in the room" mentality and he frequently credits the experience and insights of his colleagues. One way this collegial approach takes form is Michel's love of basketball—how the game flows from one player to another. Michel says, "One player can win a game, but we'll never win the championship. As a team being complimentary, we can make a difference." This makes me think of Dean Smith, one of the greatest college basketball coaches during his tenure at the University of North Carolina. Yes, he could have run the entire UNC offense through superstar Michael Jordan, but in his book, the Carolina Way, Smith talks about teamwork, including his requirement that when one of his players scored, that player would immediately "point to the passer" to acknowledge the importance of unselfish team play. For Michel and his teammates at iTeos, this means playing together and keeping their eyes on the prize, delivering medicines to patients in need.
:I'm John Siimboli You're listening to BioBoss.