BioBoss
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Hartmut Ehrlich: CEO of Abivax
Hartmut Ehrlich, CEO of Abivax, shares his thoughts with BioBoss host John Simboli about leadership in biopharma and how Abivax is working to develop treatments modulating the body’s natural immune system to treat patients with chronic inflammatory diseases, viral infections and cancer.
Today I'm speaking with Hartmut Ehrlich, CEO of Abivax, headquartered in Paris. Welcome to BioBoss, Hartmut.
Hartmut Ehrlich:Thank you very much, John. It's a pleasure.
John Simboli:What led you to your role as CEO at Abivax?
Hartmut Ehrlich:Well, maybe I should start by saying that I spent most of my professional career and that means over 35 years, actually in large pharmaceutical companies, and before Abivax I was head of Global Research and Development at Baxter Bioscience for almost 20 years, where I managed a portfolio of over 50 programs in non-clinical and clinical development, which then, after my departure from Baxter was sold to Shire. And another year later, as you probably know, Shire was sold to Takeda. And after such a long time in big pharma, and I had been with Novartis before I had been—actually before Novartis, so it was the old Sandoz. And then I also have been with Eli Lilly, before, so I was really looking for a new challenge in a smaller company where decision making process processes are much less complex and shorter compared to large pharma. And also, of course, having responsibility for all functions within the company, if you want. So Abivax was the right opportunity at the right time and exactly what I was looking for. And the only regret I have is that I did not take this decision to go to small earlier,
John Simboli:When you had made that decision that you were at least going to consider moving to a smaller company but hadn't yet decided which one, what was that process like? Or did the process suddenly present itself in the form of a call from the founder? How did that play out?
Hartmut Ehrlich:I was ready to move. But the real move came about when I was approached by the founder of Abivax. I got the call from Paris to explore whether I would be interested in leading the company. And the answer, after looking into this with a lot of due diligence, was clearly a yes, for me.
John Simboli:So the picture you had formed of what it might be like to lead a smaller biopharma company, a growing biopharma company versus what you'd experienced at Baxter, that picture that you had, how accurate was that compared to what you experienced after you became CEO?
Hartmut Ehrlich:I think I was pretty much prepared for most of the elements that are an intrinsic part of the job. Of course, when you're working in a large company, you very often meet with biotech CEOs, etc. And from these discussions, you get a pretty good picture about what is important, how are the different views between large pharma and biotech on some of the activities. And actually the biggest difference between the two jobs, that I did not realize when I took the decision, was the constant need to be engaged with investors, which, however, is something that I must say I really enjoy because it gives me and the team members that that are participating in these meetings, a fresh perspective on the company and what the view from the outside in, through the through the investors, what is really important. And that was a learning that I really appreciated and that I still value, and you can imagine, after our successful 130 million euro capital raise. I think this is an example of the kinds of activities that are very specific for biotech companies, and are an activity that I really enjoy. The decision making process or processes, especially in a smaller company, that was something that I was really looking forward to. And it didn't catch me by surprise, because I came to the job with the expectation that one of my key tasks is to find a resolution between different opinions in a management team, and to work with the management team to sort out these differences and find the best way forward to the company.
John Simboli:When you first made that decision, you wanted to lead Abivax, were you thinking to yourself anything like maybe I can accomplish something here that I can't accomplish someplace else? Was there something in particular about Abivax that spoke to you and said, this is an unusually good fit?
Hartmut Ehrlich:Abivax caters to my preferences. We are a very small company. I mean, between employees and contractors, we are about 50 people. That also entails that there is a strong commitment from our employees. And there's also strong support from our board and our investors who all believe, actually, in the potential of obefazimod.
John Simboli:When you're working for a big pharma company, and someone says, someone you've met, perhaps socially, says, Oh, I think I understand what Hartmut does, he works, for and everybody knows the name of the company. When they don't know the name of the company and you say, This is what I do. How do you explain what it is that you do each day to someone who says what have you been up to?
Hartmut Ehrlich:I am the CEO of a small Paris-based biotech company with a very promising drug candidate in phase 3 clinical trials for the treatment of patients with ulcerative colitis. So that's essentially the bare minimum. But then of course, you typically have more time than you would normally have in an elevator speech. So as many people do not know what ulcerative colitis is, I can seize the opportunity to sensibilize them for this very, very debilitating disease. So I tell them that I'm sure that they know at least one or two people who suffer from this chronic inflammatory bowel disease, but that patients do not talk about it. As we all know, the symptoms are very cumbersome for the patient. But interestingly, once people know about ulcerative colitis or the sister disease, which is Crohn's Disease, or we can also say the other side of the coin of inflammatory bowel disease, people often find out that they have acquaintances, friends, colleagues, relatives, suffering from it, without them initially being aware that the other person indeed has this disease. So this is all part of an ongoing education about the disease and creating an understanding for the problems that people who are suffering from this disease are having.
John Simboli:After that description, do you think that, I know it varies according to the person to whom you're speaking, but do you think people picture you in a lab? Do you think they picture you in a conference room giving orders and when they try to locate you as the CEO of a biopharma company? How do you get across what it is you do each day?
Hartmut Ehrlich:The people that I'm typically talking to are usually realizing what the job of the CEO is about. And this is about bringing all the talent in the company together to strategically, essentially align the forces that we have within the company. And so they realize that this is nothing that you can do on the side, this is a full-time job, working with the team, but also working with the board, working with investors, etc, which is clearly the essential part of my job.
John Simboli:I've heard that described as storytelling, that the main job of a CEO is aligning forces, as you just described, but there's also this other component of telling the story. And I don't mean that in a fictional sense, of course, but it sounds like from what you said at the beginning, that you enjoy talking with investors and telling them that story.
Hartmut Ehrlich:Absolutely. And I think wouldn't be good in my job, if I wouldn't enjoy this. And also, as this is such a necessity for me, I think I will take this a step forward and say, if I wouldn't enjoy this, I really wouldn't be suitable to function in my role of CEO. When you are faced with bringing this story of the company, the story of the product, the story of the patients across to any kind of audience, whether these are investors, whether these physicians that are interested in participating in a clinical trial, whether this is your own team, storytelling is really critical, from my point of view, so that your audience is getting the real essentials about what you do. And this is far better accomplished, by providing examples by providing stories than just presenting the facts. For example, the mechanism of action of of ABX464, which goes into a lot of biology and biochemistry. And if you can bring this across in a way that even complex mechanisms can be understood, especially from the way of where do they lead to? What does it mean to the patients, for example? That is something from my point of view that is essential in bringing a message across.
John Simboli:In my experience, the people that I've met who have become biopharma CEOs often come from big pharma, or other places where they were in a more secure environment. And you can define secure in lots of different ways. And it occurs to me, working alongside some of these folks, that this is a very hard way to make a living, because the chances of success are not high. There's so many people trying new ideas. It's almost by definition, it's an extremely difficult task. So my question is, why? Why does one choose to do something so hard?
Hartmut Ehrlich:That's a very interesting question that I must admit, I never asked myself. For me. It has a lot to do with leadership. And I really enjoy leading a very competent group of people, experts in the field. And by the way, my mantra is that every single individual in my leadership team, for his specific area of expertise, has to be better than I am in this particular area, to play the role that I'm expecting from these individuals. So I think, for me, it's an interesting leadership challenge. It has to do with not being afraid of having to deal with complexity. And around the leadership, then again, having a personality that is actually characterized by deriving transparency in the team, and as a consequence, open discussion in order to get the best outcome for the organization. And that also means that there is an overriding principle to me that communication is absolutely critical for the success of the organization. And that means, for my own personal success. I believe, and this is something that is also important when you ask, what really counts, leading by example and being authentic is absolutely important. Because I see, the team and myself together, trying to, as I mentioned, to get to the best outcome for the company, and that can only be accomplished if I trust my team. And if I'm not afraid of really being authentic when I interact with the team, and really driving the team to full transparency, I would add to this, I think, lack of fear. I would say people who are not very optimistic, for them, there is really not much of a role in leading a company, as you said, in this space. Because if you look what the chances are for you to ever be able to participate in a successful development program, and you know that very well, I suppose, these chances are actually relatively slim. So even moreso that is a very rewarding factor in the team, driving a promising compound into the last stage of clinical development, phase 3, and then collecting the data and applying for registration. This is actually very, very motivating for the team. But if you are a person for whom the glass is half empty, that may pose a substantial hurdle in being successful in this role, because as we all know, positive energy, the ability to carry other people with you, to have them experience how can you remove obstacles, et cetera? I think this is so important in this role.
John Simboli:I know just from reading a little bit about your background, that you're a physician. Did you go through anything that was like that transition from helping an individual person in a remarkable way to potentially helping a lot of people in a remarkable way?
Hartmut Ehrlich:The idea to provide new therapies for patients who currently are basically left alone with the disease is so rewarding. And of course, I had this previously in my life. For example, when at Baxter, we introduced the first recombinant and then the second recombinant factor VIII product for patients with hemophilia. And, of course, these were products, because they were not made with any kind of human ingredients, that presented a very different level of safety for the patients. This is something that from my point of view, attracts me more than treating individual patients, providing new or improved, and improved can mean efficacy, improved can mean safety, as I as I mentioned, or improve the products to the patients. that actually take away their major fears. In the case that I just mentioned, it was clearly the fear of being infected with viral diseases. When patients were treated with plasma-derived products, as we know from the 80s, so that this evolution to then recombinant products was really beautiful to see from the point of view what it did for patients.
John Simboli:Can you recall when you were eight or nine or 10, did you have any kind of self image that you can remember now about what you wanted to be as an adult? Perhaps what you thought your parents thought you should do? And does that have anything to do with what you're doing now professionally?
Hartmut Ehrlich:I was not really following a peculiar lead at this particular age. So I can remember then, when I was 15, or 16, and in the last years of high school, that was the time when I started to seriously consider becoming a physician. This was then what I wanted to accomplish. If you allow me, I'll give you a very personal vignette here. I was always a good student in school. But I wasn't sort of the the absolute top. And so my grade point average at the time was certainly not sufficient to go directly to medical school after I received my high school diploma, therefore, I decided in the last year of high school to actually not go for the final exams, but ask to be put a year back in school. So I had another shot at my grades. And so, as it happened, I was very lucky because there was a lot of appreciation for this from my teachers. In the end, I got the great point average that I needed, and was able to go straight to medical school after my my high school diploma.
John Simboli:That squares with my image of what it takes to be a successful CEO, in some ways, in biopharma, I would call it, not intentionally referring to a religious idea, but a messianic principle, you have to believe in a long term possibility.
Hartmut Ehrlich:I fully agree with you. And I think it is also really critical at certain stages of your life to take certain risks. Nobody could guarantee to me that this would be successful, this approach to step back one year in high school. And actually, there were several people that told me why did you do it? Why did you not do what most of the people did who were in a similar situation? They graduated and then had to deal with a waiting list for medical school for about five or six years. I saw the opportunity, I figured it's entirely upon me. And of course, on my teachers. I realized that risk taking is an essential part of life. And if you are a person who is not afraid of taking risks, then this is really the right path forward. And as you could see, I ended up as a CEO,
John Simboli:When you're trying to give a very short defined, structured description of what Abivax is, how do you like to answer that when someone says, Who is Abivax? What do you say?
Hartmut Ehrlich:We are a French biotech company, founded in 2013 and listed at the Euronext Stock Exchange in Paris since 2015. We have a small but very dedicated team of roughly 50 employees and collaborators and are supported by top tier U.S. and European investors.``
John Simboli:Why is it that patients need something that you hope to be able to deliver to them? What is the gap?
Hartmut Ehrlich:The gap is based on the spectrum of current treatments. Inflammatory bowel disease, whether we talk about Crohn's or whether we talk about ulcerative colitis is a disease that massively impacts the patients. And whereas there were relatively few treatments that provided some kind of amelioration of symptoms before the advent of what we now call advanced therapies, monoclonal antibodies, JAK inhibitors, S1P inhibitors, etc. The fact is that patients with this disease, there is no cure. With what we know today, we simply cannot cure the disease. So then you ask yourself, what is the situation about the patients if they take state of the art therapies, and then you realize that treatments that have been introduced since the early 2000s, with HUMIRA and Entyvio, Stelara and others, you realize that these treatments bring something between, I would say 10 and 20% of the patients into a remission status within eight weeks of taking the product, but that only and that may be surprising that the percentages are relatively low. But this is basically sort of the initial phase of the treatment and you learn do patients respond to this treatment, even if they don't get to a remission. And therefore, the critical step is when you continue treatment, then to see that after one year, you will have as many patients in clinical remission, and clinical remission means almost complete absence of symptoms. And also a clean endoscopy. Really patients will tell you not only how well they tolerate the treatment, but also how they benefit from the efficacy, because this is something that is, of course, very important that the key symptoms. And the key symptoms are related to many, many stools that these patients have per day, and also to the blood that is often in the stools and the consequences from that. They typically get weaker and weaker. And patients that feel well on treatment, that is what we are trying to to accomplish. And so we have been seeing, and this is data that we were able to publish last year in September, in the in the Lancet, Gastroenterology and Hepatology, which is a very, very reputable journal, where we published our data that we bring essentially 66% of the patients that start long term treatment, or as we call it maintenance after eight weeks, at the end of the first year, roughly two thirds of the patients 65-66% of the patients are in clinical remission. This is not seen with most of the other drugs where you typically have remission rates after one year between 20 and 40%. And you see this with patients, if therapies don't work because then they get on the next version of advanced therapy and then maybe on a third version, but they are never really recovering from the symptoms of the disease and often the only option, treatment option, that is left for the treating physicians is actually to recommend collectomy, which as you know, then brings its own sequence of issues related to the stoma, etc etc. So, what we want to do is basically enable as many patients as possible to really enjoy their lives, having a high quality of life, because they are not basically impacted by the severe nature of the disease. The clinical data so far looks very promising. So, for us the job is now to complete the phase 3 program and see that we can get the product to the patients that need it as quickly as possible.
John Simboli:And what is it about the mechanism of action that gives you hope that you can bring this this relief?
Hartmut Ehrlich:It is a new mechanism of action. Now, that of course, is not the only thing that counts, but when patients have been treated with antibodies against the let me say tumor necrosis factor alpha, like HUMIRA or the the anti-integrin antibody, etc, when you deal with monoclonal antibodies, you're always shutting down one pathway completely. And this is very, very different for ABX464. Because, and this was not engineered by us, this was discovered while we were working through the mechanism of action. What obefazimod actually does, it leads and I save you the biochemical and biological details, although this is a very very interesting process, but it leads to the generation of a small micro RNA that is called MiR-124. And I really want to use language as simple as possible. So, what do micro RNAs do in general? And just on the side, there are more than 1000 micro RNAs known and they all have very specific function and this is determined by their structure and structure determines what molecules they are binding to. For MiR-124, for the micro RNA that is heavily upregulated in our case, micro RNAs actually bind to messenger RNAs and you know messenger RNAs are bringing the genetic information from the nucleus to the cytoplasm, where protein synthesis takes place. And this protein synthesis is impacted by micro RNAs in general. And specifically, the synthesis of a number of proteins involved in inflammatory reactions or processes is specifically inhibited by MiR-124. It binds to what we call the target gene, so, the target mRNAs, and prevents the translation from RNA into protein on the sides of the ribosomes. And this means that the effector molecules, which are responsible for the symptoms in these patients, are reduced from the point of view of them being generated. So we don't use a hammer to block one particular pathway or one molecule, we use a broader approach and we compare it with a car where actually when you break, you really better apply the brake to all four wheels, instead of just one, one or two, because the consequences can be very dangerous. So we are not reducing, like this is the case for monoclonal antibodies, we are not reducing the molecular targets by 100%. This you can accomplish with monoclonals. We are typically reducing them. And just to name a couple of examples. IL17, IL23, IL6, we are reducing them to the level that you find normally in patients, and we consider this is very, very important not only from the point of view of efficacy, but also from the point of view of safety. Because if you block a molecule to 100%, tumor necrosis factor IL6, these molecules don't only have bad consequences, these are molecules that were initially generated in the body to be helping with host defense and other processes. And we don't want to shut this down completely, because then you get to potential side effects like immuno-suppression, which then can lead to opportunistic viruses, for example, to grow. So the mechanism of action, as we see it through, I would say the moderate downregulation of several of the key cytokines that trigger chronic inflammation. This really is important for us, and we believe has a major impact on the clinical picture that we are seeing in patients. And I'm glad to say that in all the patients that we have been treating so far, which is more than 1000, out of which more than 200 for longer than one year, we have not seen any imbalances between placebo group and active group when it comes to, for example, opportunistic infections. And actually we have not seen any kind of unlimited growth of viruses or bacteria as you would expect in sepsis. So that validates, the safety finding validates our conclusions from the mechanism of action on why obefazimod is such an effective, but also relatively safe molecule.
John Simboli:How does the pipeline express your vision for Abivax?
Hartmut Ehrlich:The good news is that many of these products, and that goes for the monoclonal antibodies when they were used first in the early 2000s, but also other molecules like JAK inhibitors, and as many of the processes, the intracellular processes in patients that lead to chronic inflammation, as many of these are very similar between very different diseases like on one hand, inflammatory bowel, especially ulcerative colitis, almost exclusively impacting the bowel, whereas other chronic inflammatory processes like the ones that are taking place in the synovia in the lining of the joints leading to a number of different forms of arthritis or other chronic inflammatory diseases, they express themselves typically very differently. But because the underlying processes, as I mentioned, are very similar molecules in this space typically can treat a number of different diseases that also have different anatomic locations. I mean, if you have joint disease, that's, by definition very, very different from inflammatory bowel disease, for example. And this is exactly the interesting question around obefazimod now, because the first indication, and that was relatively clear to begin with, we explored was ulcerative colitis, it worked from the phase 2A study on. When we went into patients we saw the positive effects on the patients, but that then also led to us asking the question, of course, which other indications should we be tackling? So, of course most of the products that work in ulcerative colitis also work in Crohn's. We had planned a development plan for Crohn's that would start like we did it in ulcerative colitis with a small phase 2A study, look for some kind of evidence of efficacy and then go into a larger study. However, even the small study will cost us about a year and a half during the development. And so, our KOLs, and that's another very important point, that you are working with KOLs who are really interested in the product, and who want to help you develop this product because, as we all know, there are so many pitfalls potentially in idevelopment, but here clearly, they told us in no uncertain terms, that we should skip the 2A program for Crohn's because the mechanism of disease propagation in Crohn's is very similar to the one in ulcerative colitis. And also, because as I mentioned before, many products that work in one disease work in the other as well. But that also brings with it a certain crux, we have been doing this small study, because it was not a bowel disease study, but a rheumatoid arthritis phase 2A study, then we saw ABX464 also working. So that now, we are dealing at least with three indications that are very interesting, from our point of view, to tackle. But here we have to now focus on the realities. And focus is absolutely important during the development process of any drug. And for us, the need to focus is even more obvious, because programs. end-stage programs, so, phase 2b3 programs or phase 3 programs in these indications, because you need to treat something between 1000 and 1500 patients, they come with a substantial price tag. So, we just completed a capital raise that I mentioned. So, this will bring us much much closer to our goal. But in addition, we are also trying to acquire funds that help us looking into the other indications, not only into ulcerative colitis that we are focusing about. And so our main discussion and the main vision for the company is, by the fall, have ideas or even implemented other ideas to collect money whether this is licensing out the molecule in specific geographies for ABX464. We are thinking for example, about Japan, which would bring in revenues, but really to generate the money that we need in order not to only develop ulcerative colitis, but also at least Crohn's Disease alongside the ulcerative colitis development plan. And that's something that we want to clarify where we are and how far we can go before the year is over. What I see obefazimod can achieve is that it will put Abivax in a position where we can provide a safe and especially long-term efficient treatment to many ulcerative colitis patients in need. I'm not saying to everyone, but the numbers that I was providing before I think pretty much speak for themselves. And this is especially, in this situation, the current situation of patients is that many of them do not respond or actually stop responding after a certain amount of time to available therapies that are currently sort of part of the therapeutic armamentarium of the gastroenterologist. It is often very lengthy for these patients to find a treatment that works, if any. And this means pain, stool urgency, bloody stools, anemia, malaise, fatigue, upper gastrointestinal pain, what all goes with this. So therefore, for us to bring more patients into clinical remission, patients that then can bank on this remission to persist for a substantial amount of time. And for most of the patients that are in remission after one year, we now have data that is telling us that this outcome is very similar after two years of treatment. And then also as you go further from our 2A study, we have some very encouraging data on patients that are treated now for more than four years and who are still enjoying the benefit of Obefazimod. And this is what we want, to basically transform these patients who are suffering from a debilitating disease, by taking one pill a day, that they are relieved from the symptoms for a long, long period of time. And, in the end, hopefully will not need to go through colectomy.
John Simboli:Hartmut, thank you for taking the time to speak with me today.
Hartmut Ehrlich:You're very welcome, John.
