Transcription

• Speaker #0

  If you want medical advance, you need to do some bad. Three months after we read out, we are going to run out of cash. We will go bankrupt. So we win together, we lose together. The tiny little biotech can actually do better in execution of clinical trials than the giant. It's like a Hollywood movie. Three days, we went from maybe we'll go bankrupt to, you know, one of the, honestly, one of the star offers at Nasdaq. Within three hours, we raised $750 million. And we had essentially more than 3 billion in demand.

• Speaker #1

  Welcome, everyone, to this new episode. Today, I have an exceptional guest. I am with Marc de Garidel. Hello, Marc.

• Speaker #0

  Thank you for welcoming me.

• Speaker #1

  Again. Again, here, two years after. You came already here two years ago. You just... started a new position as the CEO of Abivax and long story short, this was a biotech in difficulties at this time and you started to raise 350 million to start the phase 3 you had positive results and then you just this summer raised 750 million which makes the story year Quite exceptional. And yes, I'm very happy to have you here today again to have the details of this story. It's a masterpiece, I think, in terms of leadership in biotech.

• Speaker #0

  I don't know.

• Speaker #1

  For the moment, yes. For the last two years, yes. The future will say that. I would like to start for like a chronologic thing, maybe with the beginning when you arrived at Abivax, the first days. Can you share a bit what you've seen?

• Speaker #0

  Sure. So, you know, I was actually lucky when I joined to be immediately immersed in the field of gastroenterology, because, again, my background was not in gastroenterology. So I was also learning as I went on. But my first days were actually in the U.S. at one of the largest congress called DDW, where I had the opportunity to meet, you know, with a number of the top KORs in the world. And where I could share a bit, thinking around what Abivax was going to go. But it was a very good foundation because I could understand more what essentially physicians wanted with the drug. And how potentially to lead this phase three to success. So that was also the foundation for establishing the strategy of the company. Because if you look back, you know, again, a couple of years ago, the company had been refinanced with essentially sort of a salvage program in September of 2022. Some U.S. investors and so forth, you know, partners, really refinanced the company with 50 million euros. And then they did, again, prior to my coming, another crossover round for 130 million euros. that was in basically in February of 2023. So when I came in, in April, again, I was lucky to have at least, you know, a bit of cash, but not enough to carry on the phase three. So DDW was very important to try to, you know, to meet the KORs, but also meet with my team, the new team, to figure out what would be our strategy. Again, at the time, there was no, when I asked, you know, where is the business plan? Where, you know, what are the plans? You know, this company was really built to sell initially.

• Speaker #1

  Yes.

• Speaker #0

  And it was not really planned to go to continue and to do the phase three. So, you know, we had to start a bit from scratch about, you know, what, you know, indication we wanted to pursue.

• Speaker #1

  Okay.

• Speaker #0

  You know, how we would go ahead, how we would develop ourselves, especially within the U.S. Because, you know, 70% of the market. for IBD is in the US. And again, the CDW meeting was the foundation. So then what we did, after we heard a lot of comments about what we could do or what we should do, as a team, we gathered together actually in the south of France and we established basically the foundation for the strategy, which ultimately we presented a month and a half later to the board. And that was actually the basis of what we would do a couple of months later for the IPO. Because when you do an IPO... You need to have a story. And it's not only, you know, a very short-term story. It needs to be also a long-term story of value creation and trying to fulfill, you know, a medical need for patients.

• Speaker #1

  On the market, yes. Okay, then you started with the science and then the finance and then, yes, operations, the teams and finding the right story. Okay. And do you remember which was the first decision you made? Okay, going to this Congress? And then, yes, starting a plant from scratch.

• Speaker #0

  Well, yeah. So I think, you know, part of developing a company is you need to have a long-term vision. Because otherwise, as the Americans say, if you don't have a vision, you may end up somewhere else. So what we did is we said first priority is really develop this drug in ulcerative colitis, where phase three was beginning. Two, we wanted to develop it in a second indication, which is a bit more serious, which is called Crohn's disease. Then we realized that the doctors at the DWU told us you need to develop combination therapy, a bit like in oncology where you combine different mechanism of action in order to improve efficacy while trying to maintain safety. And the fourth pillar of the strategy was try to develop a new compound for a drug. Because in the south of France, in Montpellier, where we have a small research center, we have a library of about 2,000 molecules that could be also helpful, you know, to keep the adventure going beyond the OB-FASI model. So that was really, you know, the foundation for, you know, having a strategy. Then the question was, how much is this strategy going to cost? And how much money do we need to raise? And we knew we could not get enough money in Europe. to for carrying the phase three and doing these other things that you described. So, you know, we built up essentially, you know, worked with banks, worked on the bank syndicates to try to access, you know, the NASDAQ. So we were actually at the end of July of 23, we did what we call test the water meeting with US investors. We got a lot of interest, actually, at the time. You know, the verbal commitment from U.S. investors was $1.2 billion, potentially, of interest, which was, you know, again, very encouraging. But a couple of months later, actually, shortly after our conversation in October, when we wanted to go public, then, as you know, there were the events in Gaza and, you know, in Israel. So the market started to fall apart. But nevertheless, we were able to raise that third week of October $240 million. Actually, that week there were three companies trying to go public, and we were the only one that actually did it. But we didn't get as much as we wanted compared to what we had in July, but enough to carry on and to execute. fully the phase three in the insurrective colitis.

• Speaker #1

  You talked a lot. I'm sorry. About a lot of things. I just wanted to, it's very, yes, interesting, but I wanted to go back to the decision of the indication to decide not to go to crown first. It was a decision, yes, related to science, to budget, to... Yes,

• Speaker #0

  it was mostly budget-driven. Yeah. Because, you know, the phase three in the insurrective colitis was going to cost over all $350 million. So... that alone.

• Speaker #1

  Okay.

• Speaker #0

  And this was the most advanced one.

• Speaker #1

  Yes.

• Speaker #0

  So it was to put priority as a second priority Crohn's and start later phase 2B in Crohn's.

• Speaker #1

  If I understand it well, you were disappointed to raise the first the first Well,

• Speaker #0

  everything is ready. It was nevertheless you know, the beginning I mean To put things in perspective, it was one of the 11 IPOs of 2023. So it was, you know, it was obviously the largest ever in the French market for a French company. So, I mean, there were a lot of satisfaction, if you will, to raise this amount. It was pretty spectacular.

• Speaker #1

  And it helped you to make the phase three?

• Speaker #0

  Yes. So from that sense, it was very good. But nevertheless... If you were looking a few months back, again in July of 23, we thought we could raise 300 million. So it was, you know, it is good, but not enough to what we had hoped for.

• Speaker #1

  Yes. And you talk about the momentum.

• Speaker #0

  Yeah, no,

• Speaker #1

  but I think... You cannot decide in the moment of the company? Yeah,

• Speaker #0

  but I think this was obviously very foundational, the fact that we got to the NASDAQ, then we could build up our US infrastructure, because until then, we were essentially 35 employees in France, and we basically built up another 35 people in the US. So we opened an office in Boston, in the suburbs in Waltham, actually, as I say, often very close to the the New England Journal of Medicine. So when we get hopefully positive phase three, we can bring back directly the printout to the New England. But we were able to recruit, I think, some very, very talented people, also some people who had been in the field of IBD. So we are able to attract some people from Arena Pharma, which had been sold just before to Pfizer. So we got, you know, a very good experience. Because, you know, one of the challenges in biotech, going from phase two to phase three, and certainly it was true for Abivax, is phase three is much harder to execute than phase two. And for different reasons. Number one, the scale. You know, phase three, for example, for us, was 36 countries, 600 centers, you know, two and a half year. program, $350 million program. The phase two was, you know, probably about 16 countries and 200 patients, you know, compared to 1,275. So, and the phase three is a pivotal study, while phase two, you can, you know, the FDA and the EMA are less regarding on how you conduct phase two. So, you know, the level of expectation. Level of demand, level of quality needs to rise significantly from phase two and phase three. And the team we had in France, although it was a good team, you know, was not really experienced to do a phase three program.

• Speaker #1

  Yes, developers, it was... Well,

• Speaker #0

  it was a clinical team. And again, there were some of the research people in the south of France.

• Speaker #1

  Yes, but clinical team for phase two. And then in the US, you... Yeah,

• Speaker #0

  so we build up, you know, the chief medical officer came from the US. We had a head of clinical operation that ultimately was in the US. So we really reinforced the head of statistics. So, you know, we really built up truly an execution machine. Yes,

• Speaker #1

  your phase three team was built in the US. Yeah,

• Speaker #0

  yeah, exactly.

• Speaker #1

  And for you, it was, yes, not a choice to try to split or to make, you had to focus on the US market. Well,

• Speaker #0

  we had to focus on the US again. partly because of the size of the market and the importance of the U.S. market in general. But the skill set, you know, there are not too many, you know, employees who have phase 3 IBD, who had the phase 3 IBD experience in Europe, unfortunately. It tended to be, you know, U.S. employees.

• Speaker #1

  Yes, it's related to the numbers of studies conducted from the U.S.?

• Speaker #0

  Yeah, I think it's also part of the fact that the big leaders in the field of IBD historically have been US-based companies. You have Gen J, you have AbbVie, for example, you have Lilly, you have Pfizer. Some of the key players are already in the US, so you need to attract some of these talents into a smaller biotech.

• Speaker #1

  Okay. And then you raised this money and you had to execute this plan?

• Speaker #0

  Yes. And then things started to get a bit complicated.

• Speaker #1

  Again?

• Speaker #0

  Again. You know, because again, the execution of...

• Speaker #1

  It seems an easy story from the outside. Yeah. Looking at you.

• Speaker #0

  Yeah, yeah. But part of, again, part of the dilemma when you are in a biotech is you are pressed, you know, to execute fast. because you run out of cash. In our case, we knew that with the $250 million we had raised, we would run out of cash actually essentially by the end of 2025. So we had only two, roughly two years of cash. So the pressure was, need to finish this study as fast as possible. That's one side. But then the other one, or has the importance of the quality of the study. And please bear in mind, this study was the second largest ever to be conducted in the field of ulcerative colitis ever. Two, what we wanted to show is that our drug, Obifazimod, was not working potentially well in what we call naive patients, so patients who are put first time on an advanced therapy treatment, but also patients who had been exposed to multiple therapies before and were failing, just as a reference. In the U.S., when you look at the U.S. patients, after three years of treatment, only 5% are on the same drug. So the unmet medical need is huge for having a drug that can help patients that have been already on an advanced treatment, but will fail quickly. This was a valuable position of Obifazima. So what we tried was not only to get these naive patients who are relatively easy to find. for execution, but also this advanced patience. And this is where, you know, the challenge was, this is where why we didn't go as fast as we thought because those patients are hard to get. But ultimately, they proved to be the winning proposition and why, you know, a few months ago, everyone was so impressed by the drug because we were able to essentially include the half of this sir. hard-to-treat or refractory population into our study.

• Speaker #1

  Oh, okay. And this is, yes, the beginning of the long-term strategy to have something really well-built for the future?

• Speaker #0

  Yeah.

• Speaker #1

  To be able to write a big story?

• Speaker #0

  Yeah, but I think the fundamental thing is you need to develop a good drug for patients. That's the foundation of everything. Yes,

• Speaker #1

  but it will get approved.

• Speaker #0

  Yes, clearly. But the differentiation... When you are in a biotech, actually as a CEO, this is one of the first questions you have to ask yourself, is are your drugs going to be differentiated with the rest of the pack? And in ulcerative colitis, there are many drugs that have been approved. But as I was mentioning just before, those drugs are essentially immunoblockers. So what they do, they work very well, very short term. but then, over time, either are. patients develop resistance. So, you know, the human body find a way to develop the inflammation across that, you know, around that pathway. That was one. Or the side effects, because they block the immune system, they create, you know, their own set of issues, like, you know, patients develop opportunistic infection, you know, they have pneumonia, they're hospitalized, and sometimes they could have even, you know, malignancy. You know, to get back to you is at the end. What you really want, you want to develop a drug that is highly differentiated and that will have this sort of nice combination between efficacy and safety.

• Speaker #1

  And you got that from the beginning and you knew it could be your winning point.

• Speaker #0

  Well, at least in the phase two, we had indication that we could get there. But what was very unique in the phase three, and I'm sure we're going to talk about that, is our phase three got... you know, even better than phase two. We had greater efficacy and safety profile was actually, to some extent, slightly better, which is very unique. And then that goes, you know, about the learning of when you design a study, when you design a phase three, you need to learn about, you know, what happened in the phase two.

• Speaker #1

  Yes, the differentiation of the phase two.

• Speaker #0

  Exactly. And to try to, you know, improve. What didn't go as well in the phase two, we try to, you know, change some of the criteria so that you have better chance of success for the phase three. Because, again, the phase three is a large investment. So, you know, again, 350 million.

• Speaker #1

  Yes. OK.

• Speaker #0

  And it's part of, you know, it's part of drug development. The secret sauce is how do you make sure that when you spend so much amount of money. You work with the experts to try to optimize the outcome, but the differentiation of the drug so that ultimately it is seen as a medical advance and not a me too of other drugs.

• Speaker #1

  OK. It's also a bet. You need also to...

• Speaker #0

  When you have a new mechanism of action like ours, indeed, it's a bet for sure. But you need to bet. Well, again, if you want medical advance, you need to do some bet. part of, again, of the art is to try to mitigate the risk of that bet. Because when you go into a new mechanism of action, for sure, you don't know, you can be 100% sure that, for example, your drug is going to be as safe as others, because this is the first time you try this new pathway. But part of the art and working with the KORs is to design a study in such a way that you try to mitigate those risks. But there is, again, no guarantee. This is part of what is wonderful in this industry, is you take risks. Sometimes it works, sometimes it doesn't. But when it works, in general, it's because you thought through what could go wrong and you try to design the study in such a way that chances of going wrong are less than maybe...

• Speaker #1

  Can you explain a bit how you worked? I don't know if you can, but... How you worked on this to transform the phase two story into a better phase three story then?

• Speaker #0

  No, I mean, the part of, you know, the recipe is to listen well to the KOLs. You know, and for example, in our case, I think what was very good in the design of the phase three is the fact that those patients. tend to receive concomitant corticosteroid treatments. So what we did is, from the phase 2 to the phase 3, we decided to reduce the use of corticosteroids from 20 mg per day to 15. So that was one. Yeah, well, to reduce, to allow... the drug efficacy to speak more by itself rather than using drugs that are efficacious, but long-term corticosteroids are not good for you. So these are the example of how you can, you know, you learn from your phase two and then you adapt it for your phase three. So that was an example. Another one where, you know, immunomodulators that were in the phase 2b which could be used like the cyoperins and we removed them from in the phase three in the phase three and what we saw in the phase three the one of the reason why people were so excited about our phase three is that when the reason when the results came out in in july late july our placebo response was the lowest ever in a phase three program so A tiny little biotech like Abivax was able to execute a study better than anybody in the history of the ulcerative colitis. So, you know, it's an interesting lesson, which goes also from the learning of the phase two, but also the focus. I think that was one of my bigger mantra, you know, what I've learned over the years.

• Speaker #1

  That's what we want.

• Speaker #0

  It is. Focus, focus, focus. I think you do a much better job when you spend 100% of your time on something versus, you know, working on 30% on three things. I think this is a, you know, the Abivax example is a fantastic one because it shows that a tiny little biotech that came out of nowhere, you know, can actually do better in execution of clinical trials than the giant, which has demonstrated it. And that's why. All the KORs, when they saw this data in July, were not only impressed by the drug's ability to function and to do good for patients after eight weeks of treatment, but also the execution of the trial was, you know, again, 36 centuries, 1,300 patients. It was a massive undertaking, even though... Coming back to one of your remarks before, it took us more time, it took us six months more than what we thought originally. So we were late compared to our original IPO plan. But at the end of the day, what counts is ultimately the quality and the results.

• Speaker #1

  Okay, yes, you have to leverage also the time and to have a bit of time if you need.

• Speaker #0

  Yeah, the only thing is the clock was ticking because, you know, three months after we read out, we were going to run out of cash and we would go bankrupt. So it was a fairly binary event for us.

• Speaker #1

  Yes, and you knew it was, yes, you didn't have choice, but you knew it was a good decision also to be able to finish this way. Yes, that's where.

• Speaker #0

  Yeah, because again...

• Speaker #1

  You knew the result could be interesting? Yes.

• Speaker #0

  Yes?

• Speaker #1

  Yeah.

• Speaker #0

  Well, we had...

• Speaker #1

  It was a result.

• Speaker #0

  Well, we had some anecdotal reports, feedback from the physicians in the various countries. They told us, you know, even though it was blinded, they said, you know, we see some patients who are very severe doing much better, you know. And that couldn't be unplaceable for sure. Right. So I think we had some confidence as to that something was going on. Now what you don't know is how good. Yes, yes.

• Speaker #1

  And you cannot change the plan in the middle. Right. Exactly. Yeah.

• Speaker #0

  Yeah. And if the results had not been good, we would have been bankrupt. So three months you said. Yes. Yeah. So, you know, it shows that, you know. What we do is meaningful, but sometimes it doesn't end well. But we are lucky to be on the good side.

• Speaker #1

  Yes, yes, yes. And yes, one thing I would like to understand also is why you decided to be such ambitious for the phase three.

• Speaker #0

  Well, I think it goes back again to differentiation, to competition. If you develop a drug... That doesn't have much value. Why do you spend 300 million to develop a Me Too? I mean, in my view, it's not very attractive. And I think, you know, one of the reasons I was attracted to Abivax is I felt, also speaking with the KRLs, this was a very different mechanism of action. This was a very different approach. It was not an immunoblocker. This could make, you know, sort of a leap. for treatment. So the excitement for, you know, every day is a life. Also for our employees is when you know you work for something which is meaningful. Yeah, that can obviously fail. But if it's successful, it can be wonderful. And this is where at least we are now.

• Speaker #1

  In the middle, yeah.

• Speaker #0

  We have only eight weeks of treatment. Our study needs to continue to, you know, to essentially a year. So we cannot say, you know, we cannot claim victory yet. But. the odds that existed before, six months ago, where a lot of people were skeptical as to whether this drug would work this way. Obviously, we've passed a big hurdle. We were in Berlin at the big congress called UEG. So we had two late breakers for us, two independent sessions, the first presentations. 700 people, so the room was full. It couldn't be, you know, when you saw the... Yes, the presence, yeah. We presented especially the detail on how drug does on various type of patients. You know, everyone has been really impressed. And this is only after eight weeks of treatment. So, you know, the feeling of accomplishing something a bit special was there. So ambition goes, you know. You need ambition in life. It's more exciting. But it's part of also the character you need to have. You need to accept that also the wish level is high and that you can fail. That's part of the adventure.

• Speaker #1

  Yes, you were the good person to be able to also get this confidence to be able to execute this.

• Speaker #0

  Well, I think the advantage I have had is that, you know, since I've been CEO for a number of years, you know, I've developed drugs before, phase three, I've done phase two. I've seen, you know, success, I've seen failures. You know, you learn also a lot through your failures. So I think, yeah, I was probably more attentive to certain things that some other people may not look at and that contributed to this. But, you know, it's not that easy. It's not an easy adventure. And, you know, there are times where you are, you know, you wonder whether you're going to make it or not. But at the end, you need to be persistent. And, yeah, have a meaningful mission, I think, fundamentally.

• Speaker #1

  Yes, but here it was making this with a really small biotech, like just starting to, yeah, starting. And it's also, yes, a risk. And you were able to make this because you add also the... the confidence, the skills, the experience.

• Speaker #0

  Yeah, and you get people around you. I mean, I think they, you know. Yes, yes,

• Speaker #1

  you knew how to execute this, yes, large kind of thing.

• Speaker #0

  Yeah, and to find the people who are able to execute. And some of the people, you know, also I brought from Syncore, were absolutely key to the success because, you know, I knew them. They trusted me. I trusted them. You know. Because in all this execution mode, What you want is to resolve the issues, you know, as fast as they come. What you don't want is to have a culture of company where people hide things because they are worried that if they do mistakes.

• Speaker #1

  Yeah.

• Speaker #0

  So, and I think...

• Speaker #1

  Every day counts, yeah.

• Speaker #0

  Yeah, so every day counts. And then you can correct. Because in these large clinical trials, again, I assure you, there are many, you know, clinical trials, we know, we face some issues, you know, on a daily basis. And, you know... how you resolve them, how you characterize them. Also, you have to differentiate what you think is sort of a systemic problem versus a very punctual problem. But if it's a systemic problem, you've got to address it very seriously and take the time for it because otherwise, you know, this can contribute to...

• Speaker #1

  Do you have an example like this? Well,

• Speaker #0

  for example, we had an issue with our IRT system. obviously you know the system that basically delivers the the the investigator drug to patients. And, you know, we had, you know, for a little while, we started to discover that some of the drug were not going to the right patients. And we, thanks God, we picked it up very quickly after one day. But, you know, we had to retrieve some of the... Yeah, some of the logistic. Yeah, and do some logistical correction. If we had not picked up... that very fast, you could potentially lose your patience. The authorities would have said this is not acceptable. So there are examples of things that happen in these large studies. That's why you need a culture of transparency,

• Speaker #1

  a culture of responsibility.

• Speaker #0

  I say often we win together, we lose together, you know. It's not, you know, it's, you know, it's, you know, this feeling we're in a special adventure together. And, you know, we're going to do a few things wrong, but let's correct them quickly and let's move on. And let's not, you know, be aggravated all the time about, you know, the mistakes we've done.

• Speaker #1

  Yes, that's part of your, yes, that's definitely part of the success. Yeah, sure. Yes, and maybe the differentiation also.

• Speaker #0

  I think that's one of the difficulties. I think, for example, in large companies, they become so political. People don't want to take risks because they think that their career is going to be affected. So there is much less, I think, agility and also, to some extent, modesty. So you need to be, I think, when you develop drugs, you need to be very modest because this is a very difficult undertaking. And, you know, the egos need to be lowered. And I think it would be much better.

• Speaker #1

  But yes, we talk about a bit of leadership, but when you arrived, you, yes, you create this, you took the person like this and you wanted to, yes, to have this mood.

• Speaker #0

  Yeah, because I was fundamentally convinced that this drug could be a really good drug. But what was evident from the past is this company was run on a very short-term basis. And when you have too much of a short-term horizon, you're not going to make the best decisions. Because again, ultimately what you want to do is to develop a good drug for patients in the long term. But this is the fruit of experience, you know. Yes, yes.

• Speaker #1

  But what I'm seeking is, you need also a good leverage, a good balance between the long term and short term. Because if you just have this choice, you need also to focus on this choice and you don't have the possibility to work on another project. No, no, no, of course.

• Speaker #0

  And I have the credibility, for example, for raising money because I had been successful before. So it is clear that... Yes,

• Speaker #1

  to explain the story, to explain the story.

• Speaker #0

  To get the trust also of investors that, you know, that, you know, I do what I say, I say what I do. So that contributed to it. But again, the role of a leader is to, you know, is to lift up the ambition. But again, and to have the ability to work, you know, to think about the long term, but for sure also. on a daily basis to address all the issues that are coming. And it's sort of constant, sort of going up and down from long term to short term. But I think if you are too short term oriented, it's not...

• Speaker #1

  What is long term for you? Like, having the drug on the market or a few years after?

• Speaker #0

  Yeah, sure.

• Speaker #1

  Of the life of the drug?

• Speaker #0

  Well, for us, it's then the life cycle.

• Speaker #1

  The life of a product.

• Speaker #0

  Yeah. Beyond the psoriasis colitis, developing the Crohn's indication, looking at the combination therapy. So, yeah, it's part of a journey.

• Speaker #1

  Okay. Can we go back to this day when you, yes, you had the readout. Yes. You discovered what it makes of the patients.

• Speaker #0

  Yes. Yeah, well, it was really a special day. So I was in the US. You know, obviously, I was, you know, my statistical team had essentially, you know, blinded the data the day before. And I had told my head of statistics to send me a message when I could come into the office to know the result. But, you know, it was actually a Saturday morning. And I said, you know, please text me when I need to come in. And so he texted me. And on the text, there was actually nothing except, you know, sunshine. So I thought that's probably a good sign. That means at least we made a statistical significant, you know, outcome. But what I didn't know is how shiny would be the sun. And so when I came in, you know, he showed me with the team, you know, these results. And what, again, was amazing is our placebo-corrected effect was 16% in those two studies compared to 12% in the phase 2b. So in other words, we had a more efficacious drug, you know, in phase 3 than in phase 2. And the history of drug development. That happens very, very rarely. So, you know, I don't have the statistics, but it's extremely rare. So the level of surprise was, you know, beyond expectation because I thought, you know, the best case was 12% to be pretty much at the same level of the phase as it has to be because that was part of, you know, the changes we made in the design of the phase three. But we had over, you know, basically overpassed any expectation. So it was fantastic. And then on the safety side, it didn't seem to have, you know, really material. adverse events that would, yeah, pretty much the same as a family. We saw, you know, some headaches, you know, early on the first week, but the last, you know, couple of days, you take Tylenol and you're all good. And the rest was, there was no incidence of really any major manifestation of side effects on anything. So, I mean, there are obviously some one-off patients that develop certain conditions, but... there were no signals of anything. So it was just an absolutely incredible time. And then as a result, so I called my CFO, I called my head of IR, I said, initially we had planned to take a week to review the data, you know, to prepare, you know, the thing and do basically the financial communication the following weekend. And what we did is we accelerated everything. I said, we need to have a board meeting, you know, on Sunday night. So, you know, so within a day we had to put all the slides together. So people were literally day and night. And we did the communication on, you know, essentially on Monday night. And on Tuesday, the stock was traded. We actually blocked respectively for 45 minutes the Euronext, our quotation on Euronext because it was too much demand. And then when the NASDAQ opened, the same thing happened for nearly, I think it was a bit less, 30 minutes. You know, there was too much demand on the stock and the stock went up that day by 600%. And 600%, you know, no stock on the NASDAQ has ever done that. I mean, for us, it was like, you know, it's like a Hollywood movie, you know. Is it true? You know, what happens is just beyond expectation. So within, I would say, you know, three days. We went from maybe we'll go bankrupt if the study doesn't work to, you know, one of the, honestly, one of the star of the NASDAQ list for the year. So that was the situation. And then on Tuesday night, because since we were listed on the French market, we could not raise, you know, what we wanted to do our follow on the same day, the first day of quotation. So we had to wait basically 24 hours per year regulation in the euro next. But that night, so we had, you know, with our syndicate of banks, we started a process to raise money. So we said, you know, we want to raise, initially we thought 200, then we said, well, probably 400 given the stock price reaction. And then what was another sort of extraordinary set of events, within three hours, we raised $750 million. And we had, you know, essentially more than $3 billion in demand. So we had to, my team actually spent more time that night to allocate the amount of money that the funds, you know, wanted to. Obviously, we were not able to meet. Well, you know, we had basically, you know, from three points. I think it was actually 3.5, ultimately to 750. So we had to divide pretty much everything by four or by five, you know, to allocate to... So they spend, you know, my CFO, my head of AR, with the banks, worked probably until 2 o'clock in the morning to allocate, you know, what could be given, you know, out of the 750 million to all these big funds. Some funds, just to give you an idea, wanted to invest 300 million. So, I mean, this was just a massive event for us and like a kind of a dream. And the good thing is we got the money and now we can carry on and execute again the maintenance, finish this essentially one year study. I would say restart the Crohn's program because Crohn's, we put it a bit on the side because again, we put all our money on Apptech. We're focused on Apptech because we knew if Apptech doesn't doesn't this v3 in uc didn't work you know would be would be dead right so so now clones and now we are doing also preclinical experiments in uh with combination therapy with other drugs so we'll report them uh early uh next year and also we are trying to figure out you know how to develop a next generation compound so yeah yes crazy week it was a crazy week yes yes

• Speaker #1

  No sleep?

• Speaker #0

  No sleep for a while. Actually, even the following two weeks, we had a lot of demand. And it's still today. I mean, it's just incredible the level of interest we have. But not only from investors. The day before yesterday, I was with the University of California, and they already want to prepare the launch for 4 million patients. their doctors, when they saw the data we presented in Berlin, are so interested. They said this drug could become the standard of care in striatum colitis. So a year and a half before launch, they really want to work with us to prepare everything. So it's obviously pretty spectacular.

• Speaker #1

  You need to get used to the normal. that's what I think let's do this okay and I think, yes, talking about this week, I think there is kind of also good communication drive. Why did you decide to present it so rapidly during the night? Is it a matter of, I don't know?

• Speaker #0

  No, it's a materiality. I think the risk was that given the quality of the data, you know, you have obviously to make sure because we are a publicly traded company. we didn't want to have any leak.

• Speaker #1

  Okay, someone to invest in.

• Speaker #0

  Someone that would get a bit overly excited, who could speak to someone to say, oh, by the way, they get great data. So it was really driven by compliance.

• Speaker #1

  Ethics. Well, compliance.

• Speaker #0

  So you need to... Compliance,

• Speaker #1

  you cannot wait to...

• Speaker #0

  No, because you have two days max by the time you get... very material information. You have two days to communicate it to the market when you're a public company. So we were kind of, but the decision, obviously, to convoke the board was to address that point because I was afraid that my team would be so excited that they would start to speak.

• Speaker #1

  And you knew, what did you expect instead of what happened?

• Speaker #0

  What did I expect in terms of...

• Speaker #1

  Yes, of, I don't know, of a reaction, of, yes, amount or reactions.

• Speaker #0

  Well, yeah, I think it surpassed our expectations because, you know, for example, in terms of fundraising...

• Speaker #1

  You let the market decide.

• Speaker #0

  Yes, sure. But we thought we could raise, again, you know, the week before, we thought we would raise 200 million. When we saw the data, we looked, we thought we will raise 400 million. And then when actually we went, it was nearly double that and we could have raised more. But then there is also a question of dilution as well. And the board had set basically sort of a max to raise. But 750 million was, you know, obviously fantastic, you know, in the history of Nasdaq, on biotech, it's in the top 10.

• Speaker #1

  Yes, ah, yes.

• Speaker #0

  It's in the history. And everything in France, it's larger. So, you know, this was just already a pretty spectacular fundraise.

• Speaker #1

  Yes, and the limitation is, yes, it's related to, you said, the board didn't want more, it's a matter of dilution, but it's also a matter of, yeah. Can you explain?

• Speaker #0

  Well, it's a good question. You know, that we thought we needed to have until the U.S. launch. The banks told us, you want to get finance until the U.S. launch, because this is the next big material event for the company. So we said 750 is what we need. And that was the end of the day, the conclusion.

• Speaker #1

  Okay, and then it means, okay, you talk about the US, launch in the US, and launch in Europe would be after?

• Speaker #0

  So because the study was done in so many countries, we can file in various different markets. So the US would be number one, then EMA would be the next one. And then we plan in 27. to go to China, to go to Japan, to go to Korea, I mean, to most of the countries, Canada and Switzerland, all the rest of the world, gradually speaking. But our view is from a corporate development standpoint is that it would be very hard for us to execute a launch, you know, everywhere. We think in the US, we need about 300 people to launch the drug. That's our current estimate. I mean, if we have to build up in every country, it would be a massive undertaking. So the execution risk, notwithstanding also the money will require to build up infrastructure in every country, our strategy is to try to find a partner outside of the US. So one company, ideally, if not, would have to split to do the product launch. But the U.S. launch is planned currently around Q3 2027. In other countries, probably, you know, in the following month.

• Speaker #1

  Okay. Then Abibax is a U.S. company?

• Speaker #0

  No, it's a French company, but it is publicly listed both in Euronext Paris and in the NASDAQ. And, you know, our operations, you know, will move gradually. We'll keep, obviously, the French operation. But the US is going to take a predominant weight as time goes.

• Speaker #1

  Yes.

• Speaker #0

  Because we need to build up, for example, the launch infrastructure. So in the US, to launch, we are again 70 people. By the end of the year, I think it would be at least 100. But we need to probably to high 200 people by the end of 27. And that would be mostly in the US because of the US.

• Speaker #1

  The headquarters are in Boston now?

• Speaker #0

  Yes. in Waltham. It's on the west side of Boston. We have a lot of biotechs. Actually, we are in a building where it's only a biotech building. So you have plenty of other startups around.

• Speaker #1

  Yes, yes. And yeah, the question is how you then, it's a normal decision, obvious decision to start, yes, with the US to have two years in advance, the drug in the US and then for clinical trials abroad. And yeah.

• Speaker #0

  Well, the U.S. market is 70% of the, you know, one of the difficulties, as you know, in our industry is the U.S. pricing is a multiple of Europe or other geographies. So what happens is in IB, in the inflammatory bowel market, the ratio, which tends to be 1 to 3 in general for drugs, in IBD is more 1 to 6. So the price in the U.S. is six times higher than in Europe. So, you know, as a biotech, you have to go where it's already complicated to develop, you know, yourself. And you need to reward investors for the work you do. So you go to the U.S. first.

• Speaker #1

  Okay. And in terms of how you were seen in the landscape of these drugs, you were seen as a biotech and now you're seen as a serious? biotech and from big pharma who are already existing in this?

• Speaker #0

  Well,

• Speaker #1

  you know,

• Speaker #0

  I think certainly there has been a mutation of how the company has been perceived. I mean, for us in Berlin, it was what was astonishing is, again, we did the two plenaries, two separate plenaries, the number one presentation on both. So we had 700 people. When our presentations from KORs were finished, half of the room got emptied because it showed that actually people only showed up for our presentation, given the level of interest. And yet we had a booth, which was, you know, I would say a third of this studio. Yeah, because when we, you know, we were running out of cash. So it's a... So when we came to Berlin, we didn't know. So we had a very little booth. Fair enough. No, but it was an amazing contrast. So on the podiums, you know, we were seen as the story of Berlin. I think that's a fact. And yet we are this tiny little, you know, company with a pretty ridiculous booth. But again, my team was wonderful. We had, I think...

• Speaker #1

  You've made the job.

• Speaker #0

  Yeah, and a lot of people came to see us.

• Speaker #1

  Yes, and yes, I'm curious also about the conversations that these big pharma can have with you, because they must be curious about how you manage this.

• Speaker #0

  Yeah, obviously, they are watching us for sure. They are certainly intrigued. I think initially the mechanism of action caused some concern on their side. Now we got this pretty brilliant data. We did, by the way, market research in the U.S. in the month that followed, so basically in August. And so we had about 70 physicians from academic centers, all of our community gastroenterologists, and they all said this drug will actually probably garner a third of the market in the advanced population, the refractory population, and about 15% in the first line. which would make it the leading drug in the future of IBD. So I think they all confirmed our intuition, which the result in July, that the results are really, you know, such that this could become, you know, the number one drug in IBD. Now, again, we need to wait for the maintenance data. Because we still have a few months to go. But that is based upon this eight-week. Yeah, the profile of the drug is seen. So I think for Big Pharma, they are going to watch us. And, you know, I have no clue what they will do ultimately. But if I were them, at least some of them, I would be very worried. Yeah. Thank you.

• Speaker #1

  But it's a... I come back to the... Yes, we will slowly... Yes, finish. I come back to the... Beginning when you decided to take this project, you knew you had in hands a lot of differentiation like this. Yes, to be able to say, OK, I could drive something which is something really different. Or what did you add in mind? You cannot imagine this, like to have one of the biggest trucks.

• Speaker #0

  I go back to the idea. The phase two was intriguing.

• Speaker #1

  OK. The way they built it and the results.

• Speaker #0

  Yeah. But the results were a bit affected, I think, because of an execution issue. And also it was during COVID where there were some questions not only on the mechanism of action, but on the dose response. So some physicians and some big pharma were concerned that when you don't have a clear dose response in a trial, that may mean that your drug has something a bit, something strange. But what I was able to find out is this question of those was mostly an issue related to the execution. Because we had done, you know, part of the sites that were involved in that phase two were in Ukraine. And in particular, there was one site, you know, again, we cannot look back with precision. because we didn't do a significant audit and things like this. But it turns out that one site really skewed the data in such a way that this dose response was sort of inversed. But again, so that was one of the noise in the phase two that you had to put a bit on the side to say what is truly the drug. versus the execution of the trial. And, you know, again, and then the bet, you know, I had made. But again, thanks to, you know, the discussion we have had with, for example, Sofinova, you know, partners, who's been very critical in that period of time. Also talking with KOLs. I became convinced that this could be noise, even though at the time I was not 100% sure. But then we, you know, thanks to my team and thanks to further work, we got clear that it was more noise and that actually there would be some dose response in the phase three trial, which we kind of saw. Yeah, so, you know, but again, at the end of the day, it's a bet, right? you have to to uh You have to say, you know, what are the plus of this drug? What are the minuses? You know, what are the risks that exist with the profile after you see the phase two? How do you mitigate those risks in phase three? And then you say, yeah, I go or I don't go. If we have not done the mitigation in phase three, you know, again, this phase three could have blown up. So even though it's a good drug. So it reminds ourselves that execution is an integral part of the success of a company. And that's why, you know, when you come back to leadership of biotech, you know, I am convinced that after the end of phase one, you know, it's very important to bring leaders who have experience in drug development phase two and phase threes. Because again, the technicality of developing a drug until phase one are very different from phase two and phase threes. And I think that's one of the challenges when you have had, for example, a founder who has done a terrific job discovering a drug and bringing it to early human clinical trials. Very often, those people are not the right ones. to continue the story simply because that's not their skill set. And that's, I think, one of the big considerations in drug development, especially when you run these very large, chronic clinical trials.

• Speaker #1

  Yes, to be able to see the risk, the balance of risk. Exactly.

• Speaker #0

  And then to figure out how to have a good team.

• Speaker #1

  Long-term opportunities. Yeah.

• Speaker #0

  And to have a good team that can develop it. Because again, at the end of the day, it's my team. I am the chief of the orchestra. I know when the music doesn't sound right, but the people who play the music is a team.

• Speaker #1

  And it's a team that makes the company successful. Yes, and you know.

• Speaker #0

  It's a team.

• Speaker #1

  Yes, yes. Thank you, Marc. I think, yes, I've had so many incredible stories in one hour. Do you have other things we missed? Other stories?

• Speaker #0

  No. Watch what's next. We'll see what happens. Yes.

• Speaker #1

  Wait. You have two years, you say now? Yeah, I have two years. See you in two years, Marc. Okay. For the conclusion of the story. Thank you, Marc. Bye-bye.

• Speaker #0

  Bye-bye.

• Speaker #1

  Thank you for listening to this episode. It was great to share this story about connection, inspiration, and creating a... positive legacy. Don't forget to subscribe to stay updated on future episodes and talk to you soon.