ABIVAX Société Anonyme (ABVX) Earnings Call Transcript & Summary

Hello, and welcome to the ABIVAX EUR 28 million Capital Increase Call. My name is Josh, and I will be your coordinator for today's event. Please note that this conference is being recorded. [Operator Instructions] I will now hand you over to your host, Hartmut Ehrlich, to begin today's conference. Thank you.

Thank you, Josh, and good morning, good afternoon, ladies and gentlemen, wherever you are in the world. My name is Hartmut Ehrlich. I'm the CEO of ABIVAX, and it is my pleasure to welcome you to this webcast around the capital increase we accomplished last week. The ABIVAX team will first present a short slide deck. And afterwards, we will shift to the discussion mode and address your questions. But first, I would like to give you a quick introduction to the company. Regina, can we have the first slide, please, Slide #3? Okay. Most of you, I suppose, have seen the slides around the key company facts. However, as you'll see in a minute, we slightly adjusted it to include the result of last week's transaction. ABIVAX was founded at the end of 2013 by Truffle Capital with the goal to bring the company to the IPO on the Euronext Paris, which we accomplished in June of 2015 with the largest IPO in biotech at the Euronext in Paris by raising EUR 57.7 million, and this still stands as the largest biotech IPO. As you know, based on preclinical and in vitro data, in November of 2017, we moved into chronic inflammation by treating the first patient in our Phase IIa clinical trial in ulcerative colitis with a readout in September of 2018, and then we continued this study with maintenance treatment. But also, of course, importantly, in May of this year, we moved into our Phase IIb/III clinical trial in COVID. So much just for the introduction. Also here, you find the shareholder structure and the market cap, which last night was standing at EUR 261 million. Major shareholders did not change, but their percentage, Truffle Capital before the raise was at 47%, it's now at 41%. Sofinnova is the second largest shareholder due to their participation in this capital raise. They basically stayed at 11% or 12%, Board and management at 8%, and the shares out in the public increased to 39%. The portfolio of ABIVAX as depicted on the next slide, Slide #4, shows a strong and diversified pipeline, but to make it clear from the beginning, the focus of ABIVAX is really on the chronic inflammatory diseases. First of all, ulcerative colitis, where the Phase IIb is ongoing but very soon will come to a close from the recruitment point of view. We recruited, at this point in time, 214 patients out of the 232 that we were planning for this study, and it is safe to assume that the recruitment will be coming to an end during the month of December. The second disease that is listed here is sort of the other side of the coin of inflammatory bowel disease, Crohn's disease, where based on the strong suggestions from our steering committee, Severine Vermeire, Bill Sandborn, [ Bruce Sans ], we decided to, next year, go straight into a pivotal Phase IIb/III study. Also running at this point in time is our Phase IIa study in rheumatoid arthritis, which is also foreseen to complete recruitment during the December time frame, so essentially before the year is over. And then there is what I would call the [ cameo ]. You see it with the 2 colors here, COVID-19. And we brought in the 2 colors: one, the orange for antiviral activity; and in blue for the inflammatory activity of ABX464. This study, which is conducted in 6 European and 4 Latin American countries is ongoing and in the middle of the recruitment. The assumption is, of course, depending on the evolution of the pandemic that we will have the readout during Q1 of next year. The rest of the infectious disease portfolio at this point in time is de-prioritized because of the work that we are doing in inflammation. The only other program that I wanted to mention with our second compound, ABX196, which is a glycolipid, an immune enhancer that we are using together with checkpoint inhibitors for the treatment of patients with liver cancer, is in a Phase I/II study that is conducted at the Scripps clinic in San Diego and also at the MD Anderson Cancer Center, and we are expecting the -- reaching the completion of the dose escalation phase before year-end. I would like to leave it with this quick introduction before we go into the details of the science, but actually, at this point in time, wanted to hand over to Didier Blondel, our CFO, to provide you with some details around the capital increase.

Thank you, Hartmut. So we are on Slide #5, Regina. So the key message of this slide is very simple. After this transaction has been completed, we are well funded to execute on our company strategy for the foreseeable future. So what you have to have in mind, and that's on the left part of this slide, is since the beginning of 2020 and including this recent EUR 28 million private placement towards [indiscernible] of investors, we've been able to collect in total EUR 84 million. So EUR 28 million are dilutive, this is capital raised and EUR 56 million are non-dilutive, and this is degradation of the various loans or grants we've been able to collect from Bpifrance, Societe Generale and Kreos again since the beginning of this year. With this money, we have established that our cash runway is extended until Q4 2021 in order to execute on the portfolio and the plans that Hartmut has just introduced to you, ABX464 in ulcerative colitis. I would just add to what Hartmut was showing that we're also planning to start actively the preparation of Phase III as early as in H1 2021. So we obviously have incorporated the money needed for these efforts in that evaluation, and we also have added naturally the prevention work for the Crohn's disease indication for this study that will start by the end of H1 next year. So what we also have in mind is that while we have the cash runway extended until Q4 2021, we consider that the next critical plan funding milestone for the company would come after the UC Phase IIb readout with ABX464, which is planned to be happening in Q2 2021, and then we think it will be the right time for us based on what we expect to be solid and positive data to conclude a partnering. If we can go to the next slide, which is providing more details on the transaction that just happened end of last week. So what we can say is that we consider that we have performed a spotless and unique category transaction during last week and will explain you why. The first information is, naturally, this transaction has been widely oversubscribed, and it's being done at market price led by ABIVAX and Bryan, Garnier. So we have received and collected high interest coming from multiple geographies, U.S. and Europe, allowing us, so the company, to select a limited number of 12 high-quality investors. We have raised EUR 28 million, which is representing 11.7% of the share capital at the end -- after the transaction has happened. And what's also important to have in mind as we had a very strong investor allocation selection process. And here, the idea for us is while we were being oversubscribed is to be able to bring in biotech specialized and renowned investors into the company's share capital. While the demand -- and given the strong demand, we have, together with Bryan, Garnier helping us about this -- of this for a cloud deal in order to enable and foster investment of large institutions. This transaction has been subscribed at market price, no discount, 0 discount was performed on the closing price at the time of the transaction. Despite, we're all are aware of this that we're going through challenging market conditions. During the same period, the healthcare and small and mid-cap indexes fell by around 10% during this week, and we want to emphasize the point out that since 2015, ABIVAX is now acknowledged the only company in the healthcare sector in France, so known as Paris, to be able to execute the capital raise without any single share price discount. So again, we think that spotless and unique transaction. Going to the next slide, please. We wanted also to underline while we having very strong shareholders already, we've been able to enhance our shareholder structure, and we wanted to share with you how this subscription has been finally completed. In total, 12 investors, 55% coming from Europe, 45% coming from the U.S. and wanted to share with you a couple of key, let's say, investors that were able to subscribe and enter capital of ABIVAX on that occasion: Perceptive in the U.S.; Life Science Partners in the Netherlands; Invus, U.S. and France; and Sofinnova, or Hartmut already mentioned, that was also able to invest during that round. After this transaction, Truffle Capital remains the largest shareholder of the company with 40.6% of the shares, again, a very strong and robust shareholder structure. Then I think I'm taking over to Jean-Marc, which will lead us in ABX464 results and prospects. Jean-Marc?

Thank you very much, Didier, and good morning, good afternoon, everybody, on this call. So on Slide 8, just a small reminder, ABX464, as you know, it's a small molecule, which is administered as an oral capsule once a day. And it's coming from the proprietary library of compounds, which ABIVAX has created with our collaborative lab in Montpellier, which now has over 2,200 molecules, which have in common to bias or modulate the RNA biogenesis, and we are working closely with other molecules with Evotec to optimize these other molecules. But ABX464 has been very well characterized. It's a first-in-class novel mechanism of action by selectively upregulating micro RNA, which is an anti-inflammatory micro RNA, that's miR-124. That's really the cornerstone of the mode of action. So far, this molecule has been administered to more than 375 patients and volunteers. We have a very good safety profile, and I'd like to immediately pinpoint -- point out here that we never saw any severe infections. We never saw any lymphopenia, neutropenia, which are the precursors of these infections. So, so far, it seems like, indeed, the molecule seems to be extremely safe. And some patients have now been already given the drug for more than close to 3 years. And indeed, as a chronic treatment, we have not seen any other adverse events coming through. The anti-inflammatory effect was confirmed first in a preclinical model, the DSS mouse model. And after that, in the Phase II induction and maintenance study in ulcerative colitis, which I will detail in a minute. And the Phase IIb study in ulcerative colitis is ongoing in recruiting 232 patients. I will give you an update on that as well as the Phase IIa in RA, which is being recruiting 60 patients. The high medical need in inflammatory disease is really -- and especially if we talk first around IBD, I mean there are 2 major shortcomings, and that's why we are doing research and clinical development in that area. Shortcomings are, first of all, in terms of safety. And I mentioned already that a molecule has not shown any signs of severe infections or any signs of neutropenia and lymphopenia compared to existing classes of drugs, which hold this as a black box. Again, shortcomings is in terms of efficacy, where we -- and despite the fact that these large new Class A biologics, JAK inhibitors have come to the market, unfortunately, as we will see when I put the data in perspective of these large classes, they cannot give a sufficient, durable clinical remission in patients nor in the induction, nor in the maintenance. I'm going to detail that in a minute. The next slide. Slide 9 shows you the data from the Phase IIa induction part of the study, where patients were receiving for 56 days for 8 weeks that were receiving in a placebo-controlled way either our molecule for ABX464, an oral capsule, given once-a-day versus placebo with an endoscopy being performed at day 0 and at day 56. Endoscopies were centrally right to avoid any bias. And what we see in terms of endpoints, in terms of efficacy, is first of all, if you look at it globally, you see that all the endpoints go in the same direction. And that was the first comment from the PI, Professor Vermeire in where she said, "Well, look, all your endpoints go in the same direction." What you can see is that despite -- the study was not powered to show any statistical significance because it's a proof-of-concept study, small number of patients, 32 patients. However, you can see 3 endpoints targeted, thanks to the difference between active and placebo, you can -- we achieved their clinical -- statistical significance industry endpoints endoscopic improvements total and partial Mayo score. But the most important, which regulators and for patients, of course, is very important is clinical remission. A clinical remission, which can be translated in late terms as a functional cure, actually, although you never get cured of this disease, but you have no symptoms anymore and your -- that's confirmed by endoscopy. And you can see that the delta between active and placebo is there 20%, 24%. And that's what we're going to look at later on -- in when we put up in perspective that actually, if that's being confirmed in our Phase IIb, Phase III, we would be doubling, just doubling the clinical remission rate after induction, which would be a major improvement for patients, of course. Clinical response is always in the range of -- that clinical response to about 30% of decrease of your symptoms is always in the range of 2/3 of the base who showed clinical response. And the placebo as well, about 1/3 of patients showed it. Of course, importantly, miR-124, which is, as I said, the cornerstone of the mode of action, and the over-expression in rational biopsies was, of course -- was visible in patients receiving treatment and not in patients not receiving the treatment. That was for the induction phase, but of course, we know that ulcerative colitis, that this disease is a debilitating disease. And you don't -- you need a solution which goes beyond the induction phase. And that's why we did this maintenance study. So all the patients who were completing the induction phase, whether they had received active or placebo or whether they had been responding or not, were eligible to go into the maintenance study. And I think most of you remember that I already mentioned in the past that 2 countries did not grant us regulatory approval to go into maintenance. That was France because of EU. If you don't have the induction data yet, we cannot allow you for maintenance. And similar from the German regulators who said yes, but the German Ethics Committee, who came up with the same comment. So after the 23 patients who were eligible, 22 enrolled into the first year of maintenance study. And out of this 22, 19 completed the first year. Now just that number, 19 out of 22 completing a full year of treatment with oral 50-milligram ABX464 capsule, just the fact that, that number already says something. The drug must be well-tolerated, and the drug must -- yes, have sufficient efficacy so that patients continue indeed to take their treatments. And that's being shown when you look at month 12. So day 0 maintenance is the end of the induction phase. Month 12 is the 12-month maintenance phase. And where you see that not only in terms of clinical remission, you see that, indeed, based who were in remission at the beginning of the maintenance, so at the end of the induction at the beginning of the maintenance, that they remained in remission over time, which is showing that the efficacy is durable. But also, the longer you treat, the more patients you have who get to that remission state, the clinical remission state. And in terms of clinical response, it's not a surprise that you have a high percentage in decent clinical response at month 12. Otherwise, they would not -- if they would not benefit clinically from this medication, they would not stay in the study. At month 24, we added there endoscopy, which was centrally read, again, to take out any bias from the data. And what we see here is that in terms of clinical remission, we have similar stage of -- percentage of clinical remission compared to month 12, and indeed, also in terms of clinical response. So this shows us the data with this Phase IIa study that we have a drug, which shows efficacy during induction, which is durable during maintenance, but which also increases during maintenance. And that we have a drug also, which is safe, and of course, as I said, already efficacious after 2 years. Now let's put that in perspective then of other large Phase III studies. I think it's important to say it's putting them in perspective, not comparing because we are a Phase IIa, and I took here the Phase III studies on vedolizumab, tofacitinib and filgotinib. And it shows on the top right, you see the delta between active and placebo, which is at 24 points after our Phase IIa induction phase. Now if you compare that or if you look at in perspective of the other Phase III studies, you see that if these were confirmed, you would indeed double at least the numbers of patients in remission after the induction phase. So that would be a major progress for pace. But then if you look at the data on maintenance, and of course, all our patients received open-label ABX464 during maintenance, but you can see that if this were to be confirmed in Phase IIb and Phase III studies, that would be a major advance, taking also into account that the patients in Phase III of these 3 compounds were only allowed to go into maintenance if they had been successfully going through the induction phase. They needed at least clinical response to be going into the maintenance study, which -- and Bill Sandborn made a comment around that at UEGW last year during the -- when we presented the data as a late breaker. He said, basically, you can half these numbers. So again, I mean, but that shows how, indeed, there is a potential improvement in terms of efficacy for all these patients. So that's on the Phase IIa, which indeed to use the comments from the PI, Severine Vermeire, these data are very impressive. That leads us to the next slide, which is Slide 12, on the Phase IIb, and the Phase IIb is in a much larger population, where we use, again, the 50 milligram, but also we double and we halve the dose ranging, which is needed for regulators, versus placebo again. As you can see, 232 patients, 58 patients per arm. And again, central reading of endoscopies. The study has been recruiting patients in Canada, Europe and in the U.S. and we are now -- and since launch time, I know that we are at 214 (sic) [ 213 ] patients randomized. The study is really recruiting extremely well and is definitely being helped by the data after the maintenance data, which we made public after 1 year and after 2 years. So investigators really want to recruit patients in this study. And as you can see, we're now at 214 (sic) [ 213 ], which means that we should definitely be able to end the recruitment in December of this year with top line data for the induction phase, which can be expected by the second quarter of next year. The sister indication, as already mentioned by Hartmut, the Crohn's disease, where investigators, KOLs, but also regulatory experts told us, don't lose your time in a Phase IIa or a Phase IIb, go straight into a Phase IIb/III pivotal study, and that's what we are working on now to -- so that this study could start at the end of the first half of next year. In parallel, as mentioned already, we are also conducting a Phase IIa proof-of-concept study in RA in 5 European countries. Our aim is to recruit 60 patients, and we have so far recruited 54 of them. And the next is, of course, the large Phase IIb/III study in COVID, which is ongoing, which is a very large study, more than 1,000 patients. And we have now 131 patients randomized in Europe and Brazil, and that's what we're going to see in the next couple of slides. So Slide 13 shows you why did we go into COVID. Well, we knew, of course, that the drug has anti-inflammatory properties. We know that from our in vivo models, but also, of course, thanks to our UC studies, which I just highlighted to you. But next to that, we also -- and that was done in the labs of Professor [ Bruno Lina ] in New York. He showed that, indeed, the drug has anti-viral activity against COVID-19. And that was done in human respiratory epithelium cells. So we know that the lungs are the first targets of COVID-19, so it was very important to have this data as well, and these data are comparable to remdesivir. Now the third aspect is that this drug could also be useful in terms of tissue repair. We know that, that has been observed in DSS model, but also in patients in Phase II of our UC study, where we saw indeed, that the endoscopies are totally clear and that the tissue repair has happened. Now for patients with COVID-19, we know the lungs are affected by COVID-19, and so tissue repair is an important element as well. As mentioned already, we have a good safety profile. We have more than 375 patients and volunteers being treated. And as I mentioned already, some of them are already reaching the third year of treatment. And of course, if you develop a drug in that indication, you have to make sure that if the data are positive, you have the infrastructure in place for manufacturing in order to be able to supply this drug for patients who need it. Next slide, Slide 14, which shows you the pathology of COVID-19. And most patient, young patients are really on the upper side. There will have mild or moderate disease, and they will recover without any sequelae. However, patients who have -- who are either above 65 years old or who have a risk factor, such as hypertension, such as obesity, such as diabetes, they can develop unfortunately severe disease, which is characterized by initially a cytokine storm and hyperinflammation. And that's where we believe our drug could work by preventing this cytokine storm through its anti-inflammatory properties, but on top of that its antiviral activities. To prevent the cytokine storm from happening, it's hyper-inflammation. And therefore, preventing all the next steps, which unfortunately, for a number of patients, leads to the, unfortunately, to the death of the patients. So the study is called miR-AGE in high-risk patients, again, as I said, prior to respiratory distress. So these are patients who are either hospitalized or not hospitalized but not in intensive care. So -- but they have to respond to the inclusion criteria, which I just mentioned, either above 65 or below 65 but then with a risk factor, which I mentioned before. The main evaluation criteria is after 28 days of treatment with 50 milligram, 5-0, the same dose, the one we used in our UC study. We're going to evaluate the absence of high flow oxygen, assisted ventilation and/or death after these 28 days of treatment with ABX464. It's a placebo-controlled study, a very large study, more than 1,000 patients being run initially only in Europe. But then the first wave was losing steam, so we went to Latin America, and Brazil is now very actively recruiting. But we're also looking at Mexico, Peru and Chile to supplement this recruitment. We plan to do an interim analysis after the first 300 patients have been dosed for 28 days in order to make sure that our calculations, semi-calculations, et cetera, are on the right track for completion. And as you can see, Parexel has been selected -- is doing the study for us in terms of CRO, which study costs, which you see there. So a very large study, which is really starting to recruit extremely well. And we -- as I said, we're going to do the 300 patients analysis and have that analysis normally by the end of this year. I'll hand over now to Didier back for the news flow.

Thank you, Jean-Marc. So this slide is summarizing the news flow of the company until mid-2021, and you will see, and you know we have a very busy time at ABIVAX and a lot of data readouts in front of us. So the key and critical milestone and readout for us is on the second line, phase -- in UC, Phase IIb data. And we plan for the readout of this study, and you heard that we are confirming and our -- that we are securing the enrollment of this study to be completed by year-end, which means that the top line data will be available in Q2 2021. So that's the key that our readout over this period. The second one we could mention and should mention is on COVID-19. Jean-Marc was just presenting the outline of the miR-AGE study. We plan to have the results of this study to come in Q1 2021 with interim analysis to be completed before. So again, busy time with 2 critical -- 1 critical readout and the readout of COVID-19 to come in H1 2021. And our last slide is a quick presentation of our management team. You have us connected over the phone, but there is also a broader team very experienced and seasoned to be able to lead the company in this very exciting times for ABIVAX.

Thank you, Jean-Marc and Didier. This completes the ABIVAX presentation. And Josh, we are ready to proceed into the Q&A part of the webcast.

[Operator Instructions] Our first question comes from the line of Bertrand Delsuc from Biotellytics.

Yes, I have quite a lot, in fact. So I will start about the COVID-19 and the preclinical results you presented in July, if I remember well, with respect to the antiviral effect of ABX464. I would like to know in which time frame do you think you could publish some of these results to support the rationale and the findings, which were preliminary at the time you presented them. Second one, still on COVID-19, if you could comment on the dynamics of the recruitment because it seemed that was quite slow at the beginning, but that it is progressively ramping up in Brazil. And if you could comment if you -- given the uptake of the pandemic in the second wave in Europe, if you, let's say, wanted to open more sites in Europe as well. And so let's start with this one.

Okay. Thank you for the questions. With respect to the results of the antiviral investigations related to ABX464, we are here in the process of finalizing the lab work, and we are anticipating that a paper will be ready for submission before year-end. With respect to your question around the dynamics of the recruitment, and indeed, this is a very dynamic field, as you said yourself, yes, the last couple of months and especially the last 3 or 4 weeks have shown us, especially with Brazil now coming on board, that we're looking forward to complete the recruitment during early 2021, of course, dependent, as we said, on the dynamics. But if you look, especially in Brazil, where we still have the pandemic in full swing, we have approximately 1/3 of the study sites initiated. We will, in the next 2 or 3 weeks, get to a full initiation of Brazil with approximately 20 study sites. And your suggestion around Europe is right on target because here, we're seeing clearly the second wave. And with the second wave, actually more interest of study sites that would want to participate. So from that point of view, these dynamics underscore what we have been saying from the beginning. This was a difficult study. I think I need to say that to get off the ground, but I think we are where we want to be. And once by the middle or towards the end of November, when we have all the study sites up and running in this project, we believe that it will -- that the recruitment will actually complete rapidly.

Okay. I have some other follow-ons. So I don't know if I can keep asking them or if we -- or if I jump back into the queue. I don't know.

Operator, do we have other questions?

We do have another question on the line. It comes from...

So maybe we go first to the other question, and then we can go back to the gentleman who just asked.

Our next question comes from the line of Eric Le Berrigaud from Bryan Garnier.

So a few questions anyway. First, 3 on the UC data and program. First of all, last presentation from you was probably on the 2-year data. And at the time, you didn't have all the details. Maybe you can share after 2 years there is still a clear signal in terms of efficacy, whether it's in pretreated or in naive patients. Second question, a word about patients now moving probably out of the Phase IIb from induction into maintenance, maybe any data to share about the rate of people moving into maintenance. Third question, just to be clear about what we can expect from the Phase IIb in terms of data early 2021 because I guess there's 2 reading after 8 and 16 weeks. So will that be pulled all together or split between 8 and 16? And are you going to wait for the 16 to publish the data? And the fourth and final one, this time in RA. Just beyond safety, which is probably the key endpoint out of the IIa data, what kind of signal are you expecting in RA to support the drug moving forward in IIb?

Thank you, Eric. And I would love to address these questions, but I think our Chief Medical Officer is much more qualified than I am to provide you with the answers. Jean-Marc?

Thanks, Hartmut. So to your question about the Phase IIa. In terms of patients who -- as you can see, there were 11 out of 16 at month 24 who were in clinical remission. From this 11, 4 were previously treated with biologics and 7 were biologic naive. Now the -- that means if 11 were in clinical remission, 5 were not in clinical remission. And from this 5, 3 had received biologic refractory and 2 were biologic naive. So I think it's quite well-balanced. We see efficacy in both groups in terms of biologic refractory or biologic naive, which is, I think, an important aspect. Of course, one patient can move to the balance a little bit more towards the one section -- one part or the other, but I think the main message is that it works in both groups prior to biologics and after biologics. In terms of Phase IIb, the Phase IIb. So patients indeed who are passed in the Phase IIa, irrespective of what they received and irrespective of their outcome during the induction phase, are -- can go into maintenance. And so far, only 2 patients have elected not to enroll into the Phase IIb. So which is, I think, a very good sign, which means that all patients were -- have been waiting in the 16 weeks because, of course, we know that 25% of them were receiving placebo. So that's, I think, a very good sign. But all of the them has chosen to -- except 2 have chosen -- who completed, of course, the induction phase. All of them except 2 have chosen to go into maintenance so far with 50 milligram. Your last question around -- sorry, your last one around the Phase IIb, 8 and 16 weeks. Indeed, that's a change compared to the Phase IIa. We still go for a hard endpoint in terms of efficacy at 8 weeks with the change in total Mayo Score. However, what we are looking at with the experience in our Phase IIa, that for some patients, it may take a bit longer to get to that reduction in total Mayo Score. So what we do is those who have an endoscopy, which indeed did not give us a sufficient reduction in total Mayo Score at 8 weeks, well, we do another endoscopy at 16 weeks only for those in which indeed the first efficacy endpoint was not reached at 8 weeks. So we do another at 16 weeks, the study is still blinded, but at least we will be able there to most likely recuperate the number of patients who will have -- for whom a bit longer time was needed to get into that clinical remission total Mayo Score reduction objective. Now we were going to give you data on the 16 weeks -- on the 8 weeks and on the 16 weeks when we present -- when we communicate the data next year in a separate trade, 8 weeks and 16 weeks. Of course, we're going to communicate them all at once, the 8 and the 16 weeks. In terms of RA, of course, safety is the first. I mean that's always for a Phase IIa proof-of-concept study. First time the drug is being given in this indication, safety is the primary endpoint, but of course, we're looking at all the traditional efficacy endpoints from which we hope to see, indeed, a signal which would allow us to go into a larger study here. Okay. Hoping that answers your questions.

Our next question comes from Bertrand Delsuc from Biotellytics.

Just to have a follow-on questions on UC. If you could provide a bit more color because there was a question about the characteristics and if there was some activity in both biologics experience and biologics naive. But what we see in the landscape is that there are, let's say, more agents or more competition among the biologics in UC with, okay, ENTYVIO, but now also STELARA and coming [indiscernible] plus the oral JAKs as well? So with respect to the population that was enrolled into the Phase IIa, what can we expect in terms of prior exposure in the populations and well in the Phase IIb? And so if we -- if you could provide some comments on that. And also, I wanted to know on the Phase IIA, the maintenance protocol was amended again to keep the follow-up ongoing because you disclosed the previous results to 24 months, if I remember well, or the 36. So I wanted to know if there was -- if the follow-up was still going on. And finally, about the preparations for the UC Phase III. When you look at the UC Phase III programs, the various ones that have been performed, the designs because usually you have 2 studies but the designs are quite different from one to another. What is your current idea on this Phase III program? How would it would be split between biologics experienced and biologics naive? Would it be mixed? If you had some guidance about how -- what it could look like.

So let me just preface the answer that Jean-Marc will be giving you by saying we strongly believe that ABX464 is a product for both second- and third-line treatment of patients with UC and probably then also the other chronic inflammatory indications that are on the radar. I think that is important. We are not trying to position ABX464 in first-line therapy because you know that with the mesalamine, the prednisone, prednisolone and other and other drugs, these are clearly penny therapies for which we do not want to compete like the other biologics and more modern therapies as well, but this only to preface Jean-Marc, who will provide the answers to your question.

Sure. Thanks Hartmut. So indeed, I mean, if you saw our presentation, our corporate presentation also shows that during the induction phase, you see that our drug works really well, both in the biologics naive and biologic refractory. We have been looking at how a population of patients was compared -- whether it was comparable, indeed, to these large Phase III studies in terms of the number of parameters, in terms of total Mayo Score, in terms of disease duration, but also in terms of biologic naive or experienced. And indeed, we are -- compare with these other Phase III studies, where, indeed, we have similar total Mayo Score, similar disease duration and also similar percentage of patients at entry biologic naive/biologic refractory, which is about 50%. We have exactly 60%. So that's what we have in terms of induction. Now what you saw is that indeed in terms of maintenance after 1 year to 2 years, and I gave you the data after 2 years, that indeed, we have patients who have been refractory, who, after 2 years, are doing extremely well. And I'll give you an example. Two patients from the principal investigator Professor Vermeire in Leuven, who are refractory to everything. There was no solution except colectomy to be done. Colectomy which is very severe intervention. And she decided that could -- of course, they much -- it could -- she -- that they could -- they would start to study. These patients are doing fantastically well. So these 2 patients, refractory to everything for them, she said. Severine Vermeire was the one who told us, well, this has been transformative for these patients because colectomy could be avoided. So indeed, it's a very important aspect that the drug works in both, as Hartmut said, in second, but also in third line. Now in terms of follow-up, of course, we -- I mean if a drug is of benefit to patients, there's no reason why these patients should not continue receiving it. And as you said, I mean we presented the 24-month data. We -- some patients will reach very soon the third year. And indeed, we have put in a critical amendment and has been approached for -- so that they could start a fourth year of treatment, which is important so that these patients indeed have access to these medications as long as they can benefit from it, absolutely. In terms of programs for Phase III, of course, that's going to be -- I would say our next step indeed is to look at what are the, of course, also in terms of regulators. And we're going to go for scientific drives, we're going to go for end of Phase IIb meeting with FDA to see what they want us to include in terms of type of patients that there shouldn't be a big surprise there in terms of the number of studies. It should be one study in North America, one in Europe. And then in terms of patient recruitment, most likely, they will ask it for similar inclusion of refractory versus biologic naive patients. But also, of course, since the check inhibitors are now licensed, and that's what we already included in our Phase IIb. There will be also patients who are refractory to that class. So I think all of that, I think we still -- I mean looking at the data, indeed, our Phase IIa with an oral treatment, which indeed is once a day, good safety profile. I can only insist on that. So far, our safety profile is really very good compared to what we've seen in other classes. We are definitely on a good road here. Of course, that's why you need to do more studies, but at least for the time being, we are definitely on a very good path.

Okay. And perhaps a last question, which is, I think, still important. You received some funding from Bpifrance for the manufacturing and the scale-up of the manufacturing of ABX464. If you could provide some comments on the progress.

Yes. Thank you. So yes, you're absolutely right. The funding we got from Bpifrance was for COVID-19 program at large, miR-AGE study. That is a part of it, but also to help ABX464 to boost development in manufacturing and other R&D activities. For manufacturing, we are currently a network of 3 CMOs or CDMOs, which are sequenced in drug substance, platform for the drug product, a platform for packaging and distribution. All the work is progressing very well. And if the additional question is, would you be ready for potential commercialization in due time once we would know about the miR-AGE study readout? The answer is yes. That's the agreement we have with Bpifrance and that we want to naturally meet and will be ready in due time.

We have another question on the line, if you'd like to take it.

Absolutely.

It comes from Andreas Bischof from Nova Funds.