ABIVAX Société Anonyme (ABVX) Earnings Call Transcript & Summary

Good morning, and welcome to the ABIVAX Data Call. [Operator Instructions] As a reminder, today's call is being recorded, and a replay will be made available on the ABIVAX website following the conclusion of the event. I would now like to turn the call over to your host, Professor Hartmut Ehrlich, Chief Executive Officer of ABIVAX. Please go ahead.

Thank you, Sarah, and good morning, good afternoon or evening, ladies and gentlemen. As Sarah mentioned, I'm Hartmut Ehrlich, the CEO of ABIVAX, and I would like to welcome you to the ABIVAX's webcast presentation of the top line Phase IIb results that we reported yesterday. I am particularly pleased that, again, we have a world-class KOL with us, Professor Bruce Sands, Dr. Burrill B. Crohn, Professor of Medicine at the Icahn School of Medicine at Mount Sinai, New York, and a member of the Clinical Steering Committee of ABIVAX in IBD. Together with 2 other members of the Steering Committee, Prof. Séverine Vermeire and Professor Bill Sandborn, Bruce reviewed our top line data last Saturday, and the steering committee was absolutely instrumental in providing the clinical perspective for the conclusions from the trial. Bruce will be available after the presentation to address your clinical questions. So without further ado, let's go to Slide #3. As an introduction, I would like to present a glimpse of the global market data for ulcerative colitis and Crohn's disease, which speaks to the very large commercial opportunity in this indication. Overall, the market size for UC is expected to grow from 6 billion to 11.7 billion by 2026 in the G7 countries,for the patients that we are targeting, patients with the -- that are treated with second- and third-line therapy. And similarly, Crohn's, the number is going to increase from 12 billion now to 14.7 billion in the same period. And you see this actually in the tornado slide that is on the screen. So importantly, The market assumptions are that with the current data that we are presenting today, ABIVAX should be able to achieve a 10% to 20% market share at peak sales, which is 3 to 4 years after launch for both indications. Moving away from our commercial assumptions and focusing on our lead compound, please move to Slide #4, which shows the key properties of ABX464. The molecule is coming from our proprietary compound library, which contains more than 2,200 small molecules that were designed with the bias to modulate RNA biogenesis. ABX464 is for once daily oral administration with a first-in-class mechanism of action centered around the upregulation of the anti-inflammatory microRNA, miR-124. The drug candidate has been administered to more than 850 volunteers and patients, to some of them daily for more than 3 years with a favorable safety profile. In the clinic, the strong anti-inflammatory effect was observed initially in our Phase IIa induction and maintenance study in patients with moderate-to-severe ulcerative colitis. Today, we are going to show you the top line results of the Phase IIb study, which confirmed and extended the 2A results. And ABX464 is now ready to go to Phase III in ulcerative colitis; and to Phase IIb/III in Crohn's. As you know, there's a high unmet medical need and commercial opportunity for novel, safe and efficacious drugs in a wide range of inflammatory diseases including UC and Crohn's. Let me now walk you through the detailed data and learnings from this study and start with the overall conclusions. The primary endpoint, which was the statistically significant reduction of the Mayo Score was met with once daily ABX464 in the 25-milligram, the 50-milligram and the 100-milligram cohort at week 8 in these 254 patients, randomized, double-blind and placebo-controlled clinical trial. And the p-value that we are presenting here was the original plan that we would meet this. But I show you the actual p-values in just a minute. And of course, this was in the intent to treat population. Second, all key secondary endpoints, including endoscopic improvement, clinical remission, clinical response and the reduction of fecal calprotectin as the biomarker in ulcerative colitis, showed significant differences in patients dosed with ABX464 compared to placebo. Also, ABX464 showed rapid efficacy in all patients, including those who were previously exposed to biologics and JAK inhibitors treatment and actually who were refractory to these treatments. The ABX464 was safe and well tolerated, and importantly, preliminary data from 51 patients treated with 50 milligrams of ABX464 in the open-label maintenance study showed further increased and durable clinical remission, an endoscopic improvement after 48 weeks. Let's go to the next slide, #5. And I will walk you through the detailed data and learnings from this study and start with now the primary endpoint, which was clinical remission. But before going there, I wanted to give you a quick update on the study design. The primary endpoint was after 8 weeks, as you can see in the little graph on the bottom of the slide. In total, there were 254 patients in 15 European countries in the U.S. and in Canada in a total of 130 study sites. There were 4 study arms, the 25-, the 50- and the 100-milligram once a day, the study was really planned to reduce the bias of individual clinical investigators in the trial. So we had central blinded reading of the endoscopies. Also, it is important to note that 85% to 90% of the patients received corticosteroids, immunosuppressants, and/or 5-ASA as background therapy during the study. Also important, 50% of the patients were refractory to biologics and/or JAK inhibitors as per the stratification. So the graph is now showing the additional clinical details I mentioned, the primary endpoint at week 8 and patients then continued with induction for another 8 weeks before all of them, independent of treatment assignment and therapeutic response were given the opportunity to enroll in the 48 weeks open-label maintenance study with 50-milligram ABX464 and actually 98% of the patients decided to move on from induction to maintenance. Importantly, despite not having received the final tables for baseline demographics, from our CRO from IQVIA, we were assured that the overall patient characteristics at baseline were well balanced between the groups. Slide 7 shows the results for the primary endpoint, the mean change from baseline for the modified Mayo Score. Clearly, for all patients, and also for the subpopulation of patients previously exposed to and failing on biologics and JAK inhibitors, primary was met with a p-value of 0.001. And for 1 group, the 100-milligram dose in all patients with a p-value of 0.01. Thus, we were able to confirm the efficacy of ABX464 in all patients with moderate to severe ulcerative colitis as well in the subgroup of patients that were refractory to biologics and JAKs, which is, of course, excellent news for ABX464. Can we go to Slide #8. Importantly, Slide #8 confirms the efficacy of ABX464 on the secondary endpoints for all -- again, for all and biologic and JAK inhibitor resistant patients. And I have to stress that the study was not powered to meet any of these secondary endpoints like endoscopic improvement, clinical remission, clinical response and fecal calprotectin. So I'm giving you a moment to look at the detailed data, which show that these endpoints were also largely met. Please keep in mind that 1 star indicates the p-value of smaller than 0.05; and 2 stars, a p-value of -- smaller than 0.01 versus placebo. I'm glad to let you know that our steering committee was very excited about this data as the values and specifically the deltas to placebo further confirmed the overall efficacy of ABX464 for the treatment of all patients and specifically also the subpopulation of patients exposed to and failing on biologics and JAK inhibitors. To quote Prof. Séverine Vermeire, the principal investigator of this study, she said the observed deltas in this ITT population are sitting in the higher range of the drugs recently approved in this indication. This is clearly consistent with the outcome of the Phase IIa study, which already at the time, showed similar results. And finally, as shown in Slide #9, we were also able to show again that the onset of the therapeutic efficacy was very rapid. As indicated by the reduction of the partial modified Mayo Score during the 8 weeks of induction treatment, you can see that the curves between placebo in yellow and the 3 active doses and here, I want to say that it may look like there were only 2 active doses, but please trust me that there are 3, which is due to the fact that they were actually overlapping, that these curves clearly started to separate after the first week of treatment, becoming statistically significant after only 4 weeks. And this delta was kept actually for the next 8 weeks -- for the next 4 weeks, so at 8 weeks. And indeed, it is important to mention that for patients, it is critical to be relieved quickly of the high stool frequency and also of rectal bleeds. This finding was already observed in the Phase IIa study and speaks to the substantial improvement of stool frequency and rectal bleeds after only a very short treatment period. With these excellent efficacy data after 8 weeks of treatment, we want to focus now on the good safety of ABX464 that we confirm in this study. And our CMO, Dr. Sophie Biguenet, will detail the safety results. Sophie?

Okay. So we are on Slide #10. And the data from the induction phase of this Phase IIb study demonstrates an excellent safety and tolerability profile, which is fully consistent with our previous studies and very promising for our upcoming Phase III program and our perspectives for market approval. No new safety signal has been identified and the overall safety profile of ABX464 in this study is remarkably consistent with what has been observed so far in previous studies with ABX464, representing a total of more than 850 patients. The overall dropout rate of 8.7% is low at week 8 despite COVID-19. The frequency of serious adverse events reported as related or not related to the study treatment was overall similar between the placebo on ABX464 at 50- and 100-milligram dose while less with 25 milligrams, respectively, 6.2% for the placebo, 1.6% for 25 milligrams, 6.3% for 50 milligrams and 6.2% for 100 milligrams. The frequency of severe Grade 3 or 4 treatment-emergent adverse events reported as related or unrelated to study treatment was similar between placebo and ABX464 25 milligrams, respectively, 4.7% for the placebo, 4.8% for 25 milligrams, 7.9% for 50 milligrams and 10.9% for 100 milligrams. No deaths and no malignancy were reported in the study. We observed similar low rates of infections between all ABX464 arms, namely 8.4% and the placebo with 9.4%. The dose of ABX464 did not have any impact on the frequency of infections. For the laboratory values monitored during this study, no clinically significant changes were observed in laboratory parameters like liver function test, hemoglobin or white blood cells, no lymphopenia, no neutropenia were observed. And this is important as the reduction in lymphocytes and neutrophils are biomarkers for immunosuppression. There are no imbalance across treatment groups with regards to the laboratory values, including placebo. If we move to the next slide. Here, we show the most common adverse events, which were reported by the investigators as related or not related to the [ study treatment ]. What is remarkable with this table is that we are completely consistent with what has been observed in previous studies representing more than 650 patients in addition to the 254 enrolled in this study where headache, gastrointestinal disorders and musculoskeletal disorders came in the same order as most frequently observed adverse events. These most frequently adverse events reported were mild to moderate in intensity. All were reversible in a few days and all were manageable with, and in most cases without OTC medications. There seems to be a dose effect on these events for headache. However, at 25 milligrams, we only see a delta of 13% with the placebo, which is less than what had been observed in previous studies for the 50 milligrams. The 25-milligram dose of ABX464 clearly stands out with safety profile observed in the placebo group, except for present headaches. The safety data will be very important for the dose selection of the Phase III program with ABX464. And overall, we feel that in this Phase II study, the safety profile of ABX464 really excellent. And with this, we can move to the next slide, and I need to turn off my microphone.

Okay. I hope you can hear me again because I would like to move now from the top line data to the final induction phase results, which are expected during the second half of June, and will include, as I mentioned before, the final tables for baseline demographics, also histology of the colonic biopsies, pharmacokinetics and miR-124 expression, which all will be important for final Phase III dose selection. Can we go to the next slide. So I'm also happy to present the, as I mentioned, preliminary data from the maintenance study, which show a further increase of the durable efficacy at 1 year. So these data from the first 51 patients out of a total of more than 200 that went on to maintenance. These were the ones that had completed maintenance in the middle of May. So these data for these patients enrolled and treated with once-daily 50-milligram ABX464 showed increased and durable clinical remission and endoscopic improvement after 48 weeks, in detail, there were 55 out of these 41 patients who actually completed the 1-year maintenance. And we saw in the ITT analysis, 53% of patients that presented with clinical remission at week 48 and 59% with endoscopic improvement. And we have this little footnote here that says irrespective of patient outcome at the end of the induction phase. And this is important because in many other trials, typically only patients with at least a clinical response after induction are allowed to be included in the maintenance. And as you can imagine, this leads to a selection and negative bias because what the patients that are selected to not become part of the maintenance study are these with poor prognosis, and that will artificially drive the remission and the endoscopic improved numbers up. Bottom line, very similar data as we had in the Phase IIa. And that actually gets me to my final slide, which is about this product now moving to Phase III, as we said, by the end of the year. It essentially summarizes patients receive oral dosing of ABX464. The primary endpoint was met. The secondary endpoints were largely met. There was a fast onset of action. The molecule was safe and well tolerated and the maintenance data speak for themselves. So during the discussion, we will certainly get the view of Bruce Sands of what these data mean However, we also wanted to provide the perspective of our principal investigator, Séverine Vermeire. Unfortunately, due to another long-standing commitment, she cannot be with us today, but fortunately, she was able to provide us with a video message to you all, which we are going to play now. Sarah, can you run the 2 videos, please?

Hello. My name is Séverine Vermeire. I am leading the IBD unit at University Hospitals in Leuven, Belgium and has been the PI on the Phase IIa and also on the Phase IIb study. I was part of the clinical steering committee meeting that met last Saturday, where the data of the Phase IIb study were reviewed and discussed. I think my overall perspective of the results of the Phase IIb study, having seen the primary endpoint and also the key secondary endpoints is very positive. I really think we have a drug for our patients with ulcerative colitis. And you know that there is a huge unmet need still despite the availability of a number of biologic agents. We see that many patients still are primary nonresponders to these biologics or are losing response over time. So we are in constant need of finding new drugs. When looking at the results, it's clear that there was, for me, no dose response effect. And it was also very interesting to see that even a lower dose than the dose that was studied in the Phase IIa, namely the 25 milligrams also showed good efficacy and an overall excellent safety profile. So I'm extremely excited. I also think when looking at what we call very stringent and objective outcomes such as endoscopic improvement that the results clearly show that ABX464 is an efficacious drug for patients with ulcerative colitis. Also, when looking at the delta between placebo and active compound, so the effect size -- we see an effect size, which is at least as good, but even a little better what we conventionally see with the other agents. So overall, I'm extremely positive with these results. They are consistent. They are really good. And also the benefits risk ratio with the excellent safety profile, I think justifies that this drug should go forward as soon as possible into the Phase III for ulcerative colitis. And likewise, we absolutely need to study this drug also in Crohn's disease. So with this, I hope this overall impression helps a little bit, and I'm looking forward in continuing the collaboration I'm having with ABIVAX. What I also want to mention is that one of my first patients who entered the Phase IIa study was a patient who had failed all available drugs and was counseled for colectomy when he entered the Phase IIa study with ABX464. That patient entered remission and is, at this moment, still on the drug for more than 3 years now and is in sustained remission. So a wonderful result. And with this, I also would like to express, of course, my hope that I can continue to be the principal investigator also for the Phase III program. It would be fantastic to see a compound all the way from the preclinical experiments to the first in disease towards real products on the market. That would be fantastic. Thank you.

Thank you. Okay. Thank you, Séverine, for this testimonial. And before we move into the Q&A, I actually wanted to ask Bruce, whether he can give us a quick summary of his perspective on the data.

Yes. Thank you, Hartmut. I think Séverine said it all very, very well, and I'll be repeating probably a lot of what she said. But these data, to me, are very compelling. They're very consistent with what was seen in the Phase IIa. They clearly showed the efficacy of all 3 of the doses that were studied. We see it with both patient-reported outcomes and with objective criteria such as endoscopy and fecal calprotectin. So these are very credible results. And with regard to the magnitude of effect, particularly given half the patients were bio exposed and really bio failure and even potentially tofacitinib failure patients, we're seeing really excellent remission response rates endoscopic improvement. So I think the data are very consistent, very well aligned. And as Séverine said, at least as good as what we're seeing for other classes of agents that we have or are coming along. And you combine that with both the safety profile, which looks quite good, and the convenience of oral dosing. I think that's really a very significant fact that you can see biologic-like effect with an oral agent. So I think all of these things combined to make this a very compelling study. And I absolutely agree that this must move forward into Phase III for ulcerative colitis and in Crohn's disease as well, where there are particular unmet needs for oral agents.

Thank you, Bruce. Thank you very much. So at this point in time, I think with the impression from the data review and your perspective, we can open the floor now for the Q&A, which, as in the last webcast, will be run by Chris Maggos from LifeSci.

[Operator Instructions] And then I'll turn it over to Chris Maggos from LifeSci Advisors to moderate.

Thank you, Sarah. There's a few clusters of questions, so I'll do my best to summarize them to keep from repeating them. So could you please tell us a bit more on the lack of dose response? And does this mean that you'll have to test lower doses in the Phase III that have been tested previously?

As you are referring to the Phase III studies, as we said, this is definitely under discussion, but will only be confirmed when we get the full data sets, including, as you will understand, the pharmacokinetics, the immune observations and also importantly, the measurement of miR-124. What is clear is that in the previous study with 50 milligrams, and we also have data for the 150 milligrams, we were not at the lower end of miR-124 expression, but we were seeing already very good responses So there is a proper -- we will certainly assess the 25-milligram dose. But then, as I mentioned, based on the additional data to come in, we are considering also bringing in a lower dose like 10 or 12.5 milligrams, but we are also considering the 50 milligrams. This decision is expected to be taken during the summer. But the important point is that going down from 50 where we see an eightfold increase in miR-124 expression down to 25, where we don't have the data yet. We are expecting a further drop. But considering the mechanism of action, it is important to realize that there is the possibility that actually an even lower dose could work.

Great. Thank you, Hartmut. [ Samir Devani ] added a follow-up question on this. Were there any particular biologics for the benefit in combination with ABX464 was not seen, and Samir is from Rx Securities.

Sorry, Chris, can you repeat the question? I'm not sure I understood it.

Were there any biologicals where a benefit in combination with ABX464 was not seen? So in patients that were taking concomitant treatment with biologicals. I think that's what he's saying.

Well, there is no concomitant treatment of ABX464 and biologics at this point in time. The concomitant treatment like in all studies in ulcerative colitis during the investigation of biologics or JAKs or ABX464 is clearly limited to corticosteroids at a low dose, immunosuppressants and 5-ASA. But there is no study that would have done a combination treatment of ABX464 with a biologic and to my knowledge, but Bruce is much more in the position to talk about this, but I'm actually not sure whether any studies combining biologics have been conducted. But Bruce, this is your call.

Yes. There are some ongoing studies where biologics are being explored in combination. Actually, I may have published one of the few biologic combination studies, which was Tysabri and Remicade before we knew about the risk of PML. But -- so as you pointed out, it's not standard. in Phase II and III to do combination trials of biologics. I think what the question I might be asking is whether prior treatment and failure of any particular biologic or tofacitinib had any influence on the likelihood of response. But my understanding is we don't have all the baseline data yet analyzed, and I don't think we know the answer yet.

Absolutely. We don't have this data but as you heard from -- as you all heard from Séverine, the patient that he specifically pointed out who has failed on essentially all biologics that were -- or that are there were out there at the time. This patient eventually then responded to ABX464. So this patient had gone, I believe, through 4 different biological drugs, had failed on all of them, was counseled for colectomy and then being put in the ABX464 study through which he was actually able to pass on the colectomy.

Next question. So Chris Redhead from goetzpartners asks, how similar were the background therapy and patient selection in the Phase IIb compared to the Phase IIa trial?

I think as Bruce just mentioned, we don't have these demographic data yet. What we can say is that the Phase IIb patients were certainly a more severe patient population simply because of the changes at -- the recent changes at FDA requiring now patients to be put in the trial that at least have a modified Mayo Score of 5. And as we said, the important message here is that despite the pretreatment, which we still will assess in detail. But despite the pretreatment of patients with biologics and with JAKs, the data in this patient group was really very, very good in the Phase IIb.

I would add 1 thing, which is, although I haven't seen the baseline data, and I don't think you have all of it. Just looking at the fecal calprotectin values, the mean changes in the range of 2,300, 2,200,suggests that they started out higher than that, for sure, which suggests that this was an extremely ill population of patients. Those are remarkably high numbers.

Okay. Mr. Smith from Smith & Co. asks why don't you calculate the endoscopic improvement on a per patient basis and not on an ITT basis, for PP basis?

Yes, this question -- Bruce, do you want to answer that? Because otherwise, Paul would be prepared for this question.

I'm not sure, you would have to explain that.

Okay. Paul?

Yes, good morning, good evening, everyone. So just the endoscopic improvement rates have been communicated according to the predefined Statistical Analysis Plan. As already mentioned, endoscopy were centrally reviewed by independent central readers. And per se are totally unbiased. And therefore, the endoscopic improvement rates were presented according to the number of available endoscopies at week 8 without any kind of imputation for missing data in order to stick to this fully unbiased report. Obviously, endoscopic improvement using imputation will be communicated as part of the final results.

I can add maybe a little guess, but I don't know for a fact. It could be that for some of the -- some of the procedures may not have been high quality enough so there may be missing data. But I think you'll have to wait for the final readout to understand exactly what happened there.

Absolutely.

Okay. And he wanted to ask as well, how do you explain that the best results achieved on an ITT basis were achieved at the lowest dose? I think you've already partially addressed that.

But I think that's maybe also for Bruce to come in though.

I don't think this study was statistically powered to make statements about 1 dose superior to the other. You can just get a general sense that they all performed roughly equivalently in my view.

And what I would add to this is as you know, the clinical remission is based on the endoscopy and the stool frequency and the rectal bleeds. which are also, of course, part of the modified Mayo Score reduction where you don't see any difference between those 2 parameters. And then, of course, also in the endoscopic improvement, you're also seeing no difference, essentially no difference for the 3 dose groups, which makes us believe that this really happened by chance and there were probably a few patients who just missed the clinical remission in the [ 50 group ] by a snitch.

[indiscernible] that interpretation.

Next question is from Bertrand Delsuc at Biotellytics. You reported preliminary data in the first 51 patients who completed 12 months of treatment with ABX464. Are the baseline characteristics in these patients aligned with the rest of the population enrolled in the open-label maintenance part? What was the status after the 8-week induction in these 51 patients?

This is, of course, an interesting question. But as you can imagine, at this stage, we don't have that data yet. We are expecting to have this data when we report for the entire population. For the entire population, the 1-year data which will become available during Q1 of next year. But I think it's interesting to say that these data are very consistent with the data that we saw in the Phase IIa study.

And he adds, when will the 16-week data be available?

The 16-week data was also not prioritized for the top line and will come during the next 1 or 2 months.

I think you may have said that you don't have the information yet. But do you know the percentage of patients previously exposed to anti-TNFs in each arm? Same for [ JAKs ] -- I'm sorry.

No, we don't know it for each arm at this point in time. That will also be part of the communication of the final induction results. But as this is such a large subgroup. I mean if you consider that we randomized 254 patients, 50% of the patients means that in the ITT, you have roughly around 120 patients that are subsequently then randomized into the 4 arms, placebo, 25, 50, 100. Our expectation is that they will come very close, but we will only be able to answer this once the full data set is available.

Okay. Next question on the statistics. What were the Statistical Analysis Plan specifications for the testing strategy on the primary endpoint, alpha value 1 or 2 sided correction for multiplicity with regard to the 3 doses tested or hierarchy.

Well, again, I'm forwarding to Dr. Paul Gineste, our VP for Clinical Operations.

Yes. Basically for our primary endpoint, as disclosed in our press release, we used an ANCOVA model, And basically, we apply a gatekeeping strategy. So the first testing was done placebo versus 50 milligrams. If positive, we went to placebo versus 100, and if positive, we went to placebo versus 25. So we did not apply any kind of adjustment for multiplicity. It was part of the ANCOVA model and the testing strategy.

Okay. Eric Le Berrigaud from Bryan Garnier asked I'm curious about Professor Sands perspective with regard to the efficacy being driven almost exclusively by bio pretreated patients. The effect is very limited in so-called naive patients. Why is that in your view? And what does this mean in terms of ultimate positioning for ABX464? Is there a risk to use it in advanced stages rather than early?

I'm not sure I agree with the questioner's interpretation. It seems to work for both naive and bio exposed. So I'm not sure I can answer the second part of the question because I don't agree with the premise of the question in the first place. To my way of looking at these data, It seems to work very well for both populations.

Thank you for clarifying. What are the possible explanations for the -- this is from Bertrand Delsuc at Biotellytics. What are the possible explanations for the clinical remission rate at 50 milligrams? Which subscore of the modified Mayo Score is in play in this arm with regard to the other arms? And is there an influence of the background therapy? Or is that more patients needed more time to be induced into remission?

Well, as we were saying before, clinical remission is defined by 3 parameters, endoscopy and stool frequency as well as record bleeds. We know for the endoscopic results that they are very similar across the groups. As you also see, actually, in the overall reduction of the modified Mayo Score between all treatment groups between 25, 50 and 100. So this actually for the clinical remission leads the stool frequency as the stool frequency and the rectal bleeds as sort of the potential [ culprits ] which is something that we are looking at, but people should be keeping in mind that these are patient-reported outcomes, which, of course, are less robust than the results of the endoscopy. And this was also the reason for Séverine Vermeire to focus on the endoscopic improvement. And may I ask, Bruce, what your sort of thought on this question is.

I think you said it exactly quickly -- correctly that basically, the patient-reported outcomes are subject to more noise than the endoscopic outcomes, which are essentially red, are very reproducible. And a little bit of difference either way can make a huge difference in that particular outcome of clinical remission. So I really put more stock in the objective outcomes, namely the endoscopies, the fecal calpros.

A question from Adam Evertts at LifeSci Capital. Can you talk a bit more about what may be required to choose a Phase III dose? Will you need any additional clinical or preclinical studies?

As -- I think that's a good question. Thank you, Adam. What we said before is still valid. And this is that we certainly need the final study results, especially as they refer to the miR-124 expression in the colon tissue, the pharmacokinetics but also the immuno monitory results that we are expecting to get. But without these results, it is very difficult to make any predictions, but we believe that with these results as they come in the next 4 to 6 weeks, we believe we will be able to derive the final concept for the Phase III study in which, as you can imagine in the decision, what to do there, not only our clinical steering committee will be involved, but also our regulatory advisers.

Are they testing the 25-milligram dose in the maintenance space asks Samir Devani from Rx Securities.

That is a suggestion that we also will be discussing but based on what we are seeing in the clinical trial for the induction that is certainly a potential option for us moving forward.

Mr. Smith is asking, how do you compare your results to the results of the -- I'm sorry if I can't say this right, upadacitinib which were 33% clinical remission, 44% endoscopic remission, 74% clinical remission. Your results were below the results of upadacitinib.

Let me start to say that upadacitinib recruited the majority of the patients actually as patients that were previously exposed. And this, as you can imagine, resulted in a substantial reduction of the placebo rate. And this is going to be included in our Phase III discussion where we will be deciding how high we take the rate, how many -- or what rate of patients previously exposed we are going to take. Upadacitinib had 70% of the patients with biologics in the trial, and that is something that we will be discussing, of course, with Bruce and our steering committee. And Bruce, if you want to add to this, please feel free.

Yes. I guess what I can add in addition to what you said is just to contextualize that upadacitinib while the treatment effects are very robust, it is a class of agents where there is concern about infection, potentially venous thromboembolism, herpes zoster, many potential side effects, which despite the purported JAK1 relative selectivity seem to be of all of the class of JAK inhibitors just as we see with tofacitinib. So there is concern for our patients with IBD that this could be an important consideration. So if this agent proved to be safer, then and it had slightly lesser efficacy even -- it still might have an edge and our patients place a very high value on safety of their treatments.

And I would not only say the safety because we also wanted to bring the patients in stable remission that we are testing with the maintenance. And I'm not sure whether you have been able to identify the results from the upadacitinib maintenance studies but considering that the Phase IIb actually was completed around 2 or 3 years ago because they already reported the Phase III data. We are wondering why there is no publication of the maintenance data, which may speak to what you just emphasized.

I cannot answer that. I have not seen those data for sure.

I think you don't have the information yet, but can you comment on the just discontinuation rate in each arm at this point?

Sorry, on what?

The discontinuation rate, the rate of discontinuation, dropout.

In the maintenance study, we said -- I think I mentioned it of the [ 51 ] first patients entering this study, 50 -- 45 completed this study. So that would mean a dropout rate during maintenance of roughly 10% or 12%, which is totally consistent with what we saw in the Phase IIa. And If we look, we have an overall dropout rate in patients during the first week of induction that is, let me just make up the numbers here, it's [ 6, 15, 22 ]. That is across all doses, 8.6%.

Okay. And Doug Miehm at RBC Capital Markets and a couple of others would like to basically invite you to speculate, to compare the efficacy that you're seeing here with approved biologics, JAK inhibitors, et cetera.

I think this is something that Séverine has done already in her statement. But also Bruce was referring to. So I don't want to comment anymore on this, but just leave it with the statement of the -- of our steering committee members.

Specifically, he mentioned related to onset of action under pMMS at 4 and 8 weeks.

I can take that on. This seems quite good to me. I think even if it's not statistically significant in this very tiny study, at day 8, I believe it is, you're already seeing trends and differences. I think in a larger study, you will see those differences. That's as fast as anything that we have basically.

Okay. Thank you for answering this Bruce. I really did not completely understand the question. Thank you.

I hope I did.

I think we got it. What was the overall agreement of the endoscopy reviewers?

Paul?

Yes, basically, we used some adjudication. So basically, it was a combination of central reads, local reads and in case of discrepancy, this discrepancy were reviewed by a second central -- independent central readers. So it's a state-of-the-art methodology. But for the time being, we don't have the agreement yet. So we will provide this as fast as the top line result -- as fast as the final result, sorry.

And what do the results of the fecal calprotectin look like in the bio exposed group?

I thought we were providing this.

No, we don't -- to answer that question, Hartmut, if I may. We don't have yet this information as part of the top line. Again, this will come as part of the final results.

But I just want to mention here that in the Phase IIa study, if you remember that after the end of maintenance, the mean, median values for fecal calprotectin for the patients where actually, after 1 year at 31; after 2 years at 35. Keeping in mind that everything lower than 50 basically says you have no IBD. Between 50 and 150 or in some publications, 200, you are considered to be borderline and real IBD starts beyond the 200. So you can see how low for this group of patients the numbers went. Bruce, did I cite or quote the right numbers?

Right.

Great. Then there's a couple of questions on partnering strategy. Or is that the plan with ABX464? And specifically, the type of deal milestones and royalties or other types of structure to the partner...

Here, we introduce Didier Blondel, our Chief Financial Officer.

I'll probably be a bit disappointing because our position is for interest. We are aware and very happy of the excellent efficacy and safety data of the study. Obviously, based on that, with the Board of Directors, the management of ABIVAX, we will contemplate the best options for the future of the company, taking into account creating the best shareholder value. Thank you.

Thank you, Didier. Doug has asked for some clarification. I think we might have covered this, but let's make sure. So in the 51 patients at year 1 of maintenance therapy, what were the clinical remission and endoscopic improvement levels at 8 weeks before entering the maintenance space?

That is data that we don't have at this point in time. But as I said, the important point for us is that for the maintenance, we took all comers that completed induction independent of the outcome of the induction. So the -- for the maintenance, we simply did not select patients with a better prognosis than the other patients that, of course, had not reached at least the clinical response. So -- and that is very important if you take this data and compare it with other clinical trials as our steering committee members have mentioned several times that for some of these studies, if you have a clinical response rate of 50% or 60%. Now that means you can essentially cut the number that is reported for clinical remission at the end of the first year for other products by half.

Another question -- are you -- we're up on the last 3 questions here, so we'll be done in a couple of minutes. Are you planning to report corticosteroid-free remission at a later state?

Yes, we do. We do as part of the open-label expansion study.

Great. And Professor Sands, could you tell us how common it is to switch between therapies between induction and maintenance in ulcerative colitis?

How common it is switch between therapies, normally, we would keep a patient on a therapy that they were induced with. The exception to that, of course, is steroid induction where the toxicity of long-term steroids is prohibited and also it's not effective as a maintenance agent. We have examples of other agents that are not good inductive agents that could be used for maintenance, namely immune modulators like [ diapurines ] or methotrexate. But for all the biologics and all the small molecules that are being investigated recently, it's really a modeler if you induce well with it, then you just continue it on maintenance.

Thank you Okay. Hartmut, the last question, what are the next milestones for the company?

The next milestones for the company are clearly moving forward with our plans to go into Phase III for ulcerative colitis and into Phase IIb for Crohn's disease, which will involve, of course, a number of agency meetings. The finalization of the protocol and then importantly, the initiation of the clinical trials, which we have been discussing before. That are the most critical milestones for us going forward.

Great. Well, with that, I think we've reached the end of the questions. Thank you both for taking the time to go through them. I'll leave you to close the call, Hartmut.

Well, I just wanted to thank Bruce Sands for making himself available for this webcast despite his crazy agenda, especially during DDW. And I think we should appreciate he also has an investigators meeting for a study that he is leading that he was able to slightly shift from the point of time. So thank you, Bruce, a lot for being available I also wanted to thank Séverine for her video message, and I want to thank all participants in this call for their interest, for the questions that were raised and look forward to have the next discussion when we again talk about such very relevant data readouts. Thank you very much. Also to you, Chris. And if anyone has additional questions, don't hesitate to shoot them to me, or to Didier at ABIVAX, and we will be providing the answer then via e-mail. Okay.

Thank you.

Thank you very much.