Abivax SA Aktie

Good day, and thank you for standing by. Welcome to the ABIVAX ABTECT Part 2 results webcast and conference call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Patrick Malloy, Senior Vice President, Investor Relations. Please go ahead.

Great. Thank you, operator, and good afternoon, and good evening, everyone. We hope you've had the chance to review the press release we issued after market close in the U.S. today, announcing the ABTECT maintenance Part 2 results, strengthening the Obefazimod safety dataset and demonstrating continued clinical benefit in refractory ulcerative colitis patients. Joining me on today's call are our Chief Executive Officer, Marc de Garidel; our Chief Medical Officer, Fabio Cataldi our Head of Global Medical Affairs, Chris Rabbat, and our Head of Regulatory Affairs, Keith Fournier. In a few moments, Marc will provide some opening remarks. And following that, Fabio will present the efficacy results. Chris will then present the safety review and exposure-adjusted incidence analysis with Keith providing a regulatory assessment.

Following their prepared remarks, we will hold a KOL panel where we are honored to be joined by Dr. Jordan Axelrad and Dr. Remo Panaccione, who will provide their perspectives on the totality of the Obefazimod data presented today. We'll then open the floor to a Q&A session with ABIVAX management and our KOL panel. Dr. Axelrad serves as Professor at the New York University Grossman School of Medicine and serves as the Co-Director of the Inflammatory Bowel Disease Center at NYU. Dr. Panaccione serves as Professor of Medicine and Director of the Inflammatory Bowel Disease Clinic at the University of Calgary.

Before I hand the call over to Marc, I'd like to remind you that during today's call, we will be making forward-looking statements. A summary of the forward-looking statements are included on Slide 4 of this deck and can be referenced in our 6-K filing.

Now I'd like to hand the call over to our CEO, Marc de Garidel. Marc?

Thank you, Pat. Today, we are pleased to present the ABTECT maintenance Part 2 results. which we believe further strengthens the overall profile of Obefazimod in ulcerative colitis. These efficacy data reinforce a meaningful clinical benefit of Obefazimod even in the highly refractory patient population. It has demonstrated best in disease efficacy, unmatched by the most efficacious treatments available today in a hard-to-treat population. Part 2, also expands our long-term safety experience with malignancy and non-melanoma skin cancer rates remaining within the expected background range of patients with ulcerative colitis. As a result, the larger safety database further increases our confidence in the long-term safety profile of Obefazimod, and we believe further derisks the regulatory pathway. Before we take you through the results in detail, I want to emphasize that this is a very unique data disclosure, sharing this level of detail at each phase of our development is unprecedented. However, we have chosen to accelerate this Part 2 readout because we believe it is important to be transparent and provide the market with a complete picture of Obefazimod benefit risk profile.

First, our efficacy story continues to strengthen. We continue to see best-in-disease efficacy in difficult-to-treat patients, including induction nonresponders. In fact, 37.2% of 50-milligram induction nonresponders went on to achieve clinical remission, and 34.5% achieved endoscopic remission at week 44 of maintenance. Those are remarkable results. Additionally, for patients who relapsed on 25-milligram in Part 1 of the study, we can now report that nearly half of them were able to achieve clinical remission at week 44 once they dose escalated to 50-milligram in Part 2.

Second, the expanded safety database gives us even greater confidence in the overall safety profile of Obefazimod. We have now accumulated more than 1,700 patient years of exposure across Phase II and Phase III. And when the data are viewed in context, malignancy and non-melanoma skin cancer incidents remain within or below the expected background rates for patients with ulcerative colitis. We also carefully evaluated the individual safety events and found no evidence of a new or unexpected safety pattern. Importantly, these findings are consistent with Obefazimod mechanism of action by enhancing miR-124, Obefazimod helps to rebalance a dysregulated immune system rather than broadly suppressing immune function. We believe this differentiated non-immunosuppressive mechanism contributes to the favorable safety profile observed across the clinical program.

Finally, we have independently reviewed the Part 1 and Part 2 maintenance safety data with multiple experts and regulatory consultants. Their conclusions have been consistent based on the data that's available today, they do not expect a boxed warning for Obefazimod. They support filing both the 25- and 50-milligram maintenance doses to address the needs of different UC patient population and believe Obefazimod has a clear regulatory path forward.

Now I would like to hand the call over to our Chief Medical Officer, Fabio Cataldi, who will walk through the Part 2 efficacy results in detail. Fabio?

Thank you, Marc. Before reviewing the Part 2 data, it is important to highlight 4 key design features. First, Part 2 serves as a supplemental data set to the Part 1 registrational cohort shown on the left-hand side of the slide. Second, Part 2 includes 2 distinct patient populations. Part 1 relapse, we were rescued with open label of Obefazimod 50-milligrams and induction non-responders who either continue their assigned Obefazimod dose or if previously on placebo were randomized to an active dose. Together, the two 50-milligram groups account for 447 or 633 Part 2 patients or about 71%. Third, these patients represent a more refractory and difficult to treat population either because they relapsed after response or did not respond during induction. Finally, Part 2 did not include a placebo arm. All patients received Obefazimod. So efficacy and safety results should be interpreted in that context.

Today, we will focus on the key efficacy and safety findings for Part 2, with additional analysis to be presented at upcoming congresses. This slide highlights the Part 2 patients were a more difficult to treat population. Over 55% have previously failed at least one advanced therapy compared with approximately 38% to 46% in Part 1. Despite this, 44-week completion rates remain high ranging from about 70% to 86% across the Part 2 groups. This context is important when interpreting the efficacy results because clinical benefit in induction respond and relapse represent a higher bar than a traditional maintenance population. It is also important to recognize that induction nonresponders that ended Part 2 had only been treated for 8 weeks without achieving clinical response. This means that they're carrying a substantially higher inflammatory burden of the start of maintenance treatment, than induction responsers, that entered Part 1. This is reflecting the baseline characteristics at the start of maintenance.

Mean Modified Mayo Score was more than twice as high in induction responders in Part 2 compared with induction responders that enter Part 1. While over 80% of induction nonresponders in Part 2 have fecal calprotectin levels above the clinically meaningful threshold of 150 micrograms per gram compared with approximately 50% in Part 1. As a reminder, we enrolled the highest percentage of JAK failures of any Phase III UC trial to date. 19% to 22% of the prior advanced therapy patients failed JAK inhibitor in Part 1 and Part 2 respectively.

Now let's focus on the Part 2 induction responders. These are patients would not achieve clinical response after 8 weeks but continued Obefazimod treatment. These 3-through design allowed us to evaluate whether longer-term therapy will provide benefit in patients who will discontinue in other Phase III programs, did not allow drug nonresponders to enter maintenance or long-term expansion. By week 44 of maintenance, efficacy was observed across all exploratory end points with numerically stronger results seen in the 50-milligram arm. In this group, 37% achieved clinical remission, 62% achieved clinical response and perhaps most impressively, approximately 1/3 achieved endoscopic remission, which is the most difficult and objective endpoint.

Although these analysis are exploratory and uncontrolled, the consistency across symptomatic and objective endpoints suggest that a meaningful proportion of initial responders benefit from continued Obefazimod treatment.

The second part population we will discuss consists of patients who initially responded to Obefazimod during treatment and were randomized to 25 milligrams in Part 1 of the maintenance study, but subsequently relapsed and received open-label rescue treatment with a higher 50-milligram dose.

Importantly, 45.5% of these patients who relapse on 25 milligrams were able to achieve clinical remission and 2/3 reestablished clinical response after dose escalation. We believe these findings are particularly meaningful because they mirror what physician encounter in clinical practice. Patients who lose response on maintenance dose often require treatment optimization rather than switching to an entirely new therapy. This data demonstrated increasing the dose from 25 milligrams to 50 milligrams can reestablish disease control in a meaningful proportion of patients.

In early June, we reported that Obefazimod delivered potential best-in-disease endoscopic remission among induction responders. Today, data showed that this efficacy stand to an even more challenging population. Patients will not respond after initial 8 weeks induction period. Remarkably, the endoscopic remission rates achieving this induction nonresponder are as high or even higher than rates reported for induction responders for other approved therapy, including Rinvoq. Endoscopic remission is an especially important endpoint as associated with lower relapse rates and improved long-term outcomes in ulcerative colitis.

I'll now turn it over to Chris Rabbat, our Head of Global Medical Affairs to walk through the safety review.

Thank you, Fabio. Now we will dive into contextualizing the safety results of the full Obefazimod clinical program. First, we'll provide a high-level recap of the key findings from the June 1 data release. Next, we'll review the Part 2 safety data with a particular focus on malignancies excluding non-melanoma skin cancers and separately non-melanoma skin cancers. Finally, we will put these findings into context by reviewing the exposure-adjusted incidence rates for these rare events across the Obefazimod program.

This slide provides important context from safety observed in Part 1 of maintenance. Overall, Obefazimod showed a favorable safety profile with infrequent serious treatment emergent adverse events, no signal for serious infections, low incidence of headache with strong treatment persistence.

Before we review the Part 2 safety data, I want to level set on one important point regarding the difference between malignancies excluding NMSCs and NMSCs. Malignancies, excluding NMSCs are the primary focus of regulatory and clinical safety assessments for malignancies. They have been associated with box warning language for JAK inhibitors and TNF inhibitors because they can result in significant impact on patients' well-being. NMSCs on the other hand, are typically evaluated separately. They have not been associated with box warning language in IBD therapies or other therapeutic areas and are generally managed through routine dermatologic surveillance, which is part of standard IBD clinical practice. When identified early, they are typically treated with local excision and have low impact on patients. Keeping this distinction in mind is important as we review the Part 2 safety findings and the exposure-adjusted incidence rates on the following slides.

Now let's put Part 1 malignancy, excluding NMSC findings in context with other Phase III placebo-controlled maintenance cohorts in UC. This comparison focuses only on the placebo-controlled maintenance period since that is the common registrational data set across programs. This table shows the percentage of patients in any active treatment arm who experienced a malignancy excluding NMSCs, or all approved UC treatments since Entyvio was approved in 2014. In ABTECT, Maintenance Part 1, there were 2 events or 0.52%, placing Obefazimod in the middle of the range. Both events occurred in the 50-milligram arm with no events in the 25-milligram or placebo arms. While this is a numerical imbalance for rare events, similar patterns have been seen in other UC programs, including Skyrizi, one of the most utilized agents available, which had the same number and event distribution with 2 events in the high dose and no events in the low dose or placebo. Overall, the Part 1 malignancy findings are consistent with the experience reported for approved UC therapies.

Before reviewing the Part 2 safety summary, it is important to consider the imbalance between dose groups, both in number of patients exposed to each dosing group, but also the cumulative duration of exposure. One way this is typically done is by utilizing the relative proportion of patient years of exposure for each group. In Part 2, the 50-milligram group accounted for 288 of the 420 patient years of exposure or nearly 70% with approximately 30% for the 25-milligram and notably, as a reminder, 0 on placebo since there was no placebo comparator for Part 2. Because more exposure creates more opportunity to observe safety events, especially rare events, they are more likely to be observed in the group with the largest portion of exposure. In this case, the 50-milligram arm. This context is important as we review the overall Part 2 safety on the next slide.

This slide summarizes the top line safety findings from Part 2. As a reminder, Part 2 did not include a placebo arm. So these results are descriptive and should be interpreted in the context of active Obefazimod treatment. Overall, TEAE rates were similar across dose group. TEAEs leading to study discontinuation were somewhat higher in the 25-milligram group, which was partially driven by a worsening of ulcerative colitis. One death occurred in the 25-milligram group and was assessed by the investigator as unrelated to treatment. The suspected cause was pulmonary embolism in a patient over 65 and with multiple pre-existing risk factors, including a prior pulmonary embolism, atrial fibrillation, type 2 diabetes, hypertension and recent prolonged immobility. Serious or severe infections and opportunistic infections were infrequent and did not suggest a dose-related pattern.

There were 2 malignancies excluding NMSCs both deemed unrelated to treatment by study investigators in patients with pre-existing conditions and multiple other risk factors. Importantly, both occurred in patients who were previously on placebo in Part 1 and experienced relapse. Since the protocol indicated, all Part 1 relapsers would receive the 50-milligram dose in Part 2, both cases landed in the 50-milligram group. NMSCs were balanced by event count with 2 cases in each dose group, acute pancreatitis was also reported once in each dose group, and there were no cardiac abnormalities suggestive of cardiac fibrosis.

Before we review exposure-adjusted incidence rates, it is important to look at how patient your exposure is distributed across the data sets we will analyze. For the integrated UC clinical program, which includes Phase II and Phase III, placebo represents only a small portion of total exposure, about 11%, while the 50-milligram dose accounts for the largest share at approximately 49%. As I mentioned earlier, this pattern is even more pronounced in maintenance Part 2 where there was no placebo arm and nearly 70% of exposure occurred in patients receiving the 50-milligram dose. Because exposure is not balanced across treatment groups, raw event counts can be misleading particularly for uncommon events. Groups with more patient years simply have more opportunity to observe rare safety events. For that reason, exposure-adjusted incidence rates relative to the expected background rate in the patient population being studied provide a more meaningful way to compare safety findings than across treatment groups with unequal exposures.

Before discussing the exposure-adjusted incidence rates for malignancies excluding NMSCs, I want to briefly note the source and interpretation of the published reference range used here. The reference range was selected based on a careful review of literature describing incidence of background malignancy, excluding NMSCs and a broad UC population, including both treatment naive and advanced therapy experienced patients. Other high-quality publications report higher rates, in some cases, more than 1.0 per 100 patient years, particularly in more refractory or heavily pretreated cohorts. For that reason, this reference range should be viewed as a useful benchmark for context rather than a statistical test of treatment relatedness.

This slide applies the exposure-adjusted approach to malignancies excluding NMSCs across 3 data sets, the full integrated UC clinical program, the combined maintenance population, and maintenance Part 2 alone at the bottom. The exposure-adjusted incidence rates for the combined active arms remained within the published UC reference range across all 3 analysis sets. Because malignancies excluding NMSCs are uncommon events, incidence rate estimates become more precise as cumulative exposure increases. The ABTECT maintenance data should be interpreted using the totality of the exposure-adjusted evidence, making the integrated UC clinical program analysis at the top of the slide the most relevant data set with 1,700 patient years of active drug exposure.

The results in this table demonstrate that exposure-adjusted incidence rates in each individual dose and the active combined treatment arms are consistent with the UC background reference range, which again, were based on published UC studies. This supports the interpretation that when adjusted for exposure, the observed malignancy rate, excluding NMSCs that were observed in all 3 data sets is consistent with the expected range for this patient population.

As noted on the prior slide, in Part 2 of the maintenance trial, there were 2 malignancies excluding NMSCs observed, both deemed unrelated to treatment by study investigators likely due to preexisting and confounding risk factors. The MPN patient had preexisting thrombocythemia at baseline with elevated platelets of 909,000 per microliter which remained elevated throughout the study until the diagnosis. And the second case was a 55-plus-year-old patient diagnosed with prostate cancer who was exposed to Obefazimod for just 3 months. Before discussing non-melanoma skin cancer, the key context is that this program used more intensive skin lesion surveillance than any of the UC Phase III protocols we benchmarked, which included all 3 trials completed since 2016.

Skin lesions were first identified as an adverse event of special interest based on a modest numerical imbalance in Phase II. Following a nonclinical photosensitivity finding, regulatory feedback led to photosensitivity being incorporated into the existing skin lesion AESI framework. The Phase III and Phase II OLE protocols were strengthened to include dedicated reporting, lesion photography, central dermatologist review and lesion-specific adjudication. Features not included in the benchmark protocols. That matters for interpreting NMSC findings. Before enhanced surveillance, no NMSCs had been reported in the UC program. After enhanced protocol-driven surveillance was implemented, NMSCs were detected, consistent with increased ascertainment.

Despite this intensive surveillance, exposure-adjusted incidence rates for the broader skin lesion AESI were similar between Obefazimod and placebo and ABTECT with no treatment imbalance. I'll detail this on the next slide.

NMSCs remain rare and were detected in patients with multiple risk factors, limiting ability to infer a causal relationship with treatment. In Phase III, 60% were identified within the first 6 months of exposure with no increase over longer treatment duration, a finding consistent with detection of potentially preexisting or developing lesions. Taken together, the timing and pattern of events are more consistent with enhanced detection from protocol-driven surveillance than with a cumulative exposure-related NMSC signal. Because skin lesions were monitored as an AESI, we can compare overall skin lesion occurrence across treatment groups using exposure-adjusted rates.

In the combined maintenance data set, rates were similar across groups, 10.2 per 100 patient years with placebo, 8.8 with 25 milligrams and 10.0 with 50 milligrams. So even with robust protocol-driven surveillance we did not observe an increase in overall skin lesion occurrence with Obefazimod. This provides important context for interpreting the NMSC findings on the next slide. If Obefazimod were increasing skin-related toxicity, we would expect to first see an imbalance in overall skin lesions. We simply do not observe that. This side applies the same exposure adjusted approach to NMSCs across the 3 data sets, the full integrated UC clinical program, the combined maintenance population and maintenance Part 2 alone. The exposure-adjusted incidence rates for the combined active arms remained within or slightly below the published UC reference range across all 3 analyses.

As with the prior malignancy analysis, the largest data set is the most informative because it includes the greatest amount of patient years of exposure and provides the most stable estimate for uncommon events. In the integrated UC clinical program, which again includes approximately 1,700 patient years of active drug exposure, the active combined NMSC incidents was 0.59 for 100 patient years which is slightly below the published UC reference range of 0.7 to 1.4. Overall, the NMSC rates observed with Obefazimod were within or below the range reported in published UC studies.

As discussed earlier, NMSC should be interpreted separately from non-NMSC malignancies given their different clinical and regulatory significance. In Part 2, there were 4 NMSCs reported 2 for each dose. All 4 cases occurred in patients with multiple established risk factors including 3 with advanced age, 3 with prior thiopurine use, 2 with prior history of skin cancer; and 3 with failure of multiple advanced therapies with an established increased risk for NMSC. With the addition of the Part 2 maintenance data, the observed safety database now includes more than 1,700 patient years of exposure. The key takeaway is the overall safety profile continues to remain favorable. Importantly, we continue to see low incidence of adverse events typically associated with broad immunosuppression, which is consistent with Obefazimod's mechanism of action and its role in restoring mucosal immune balance without evidence of broader immunosuppression.

We also evaluated malignancies using exposure-adjusted incidence rates. Rates for both NMSC and malignancies excluding NMSCs were consistent with expected background rates in a UC population. Taken together, the expanded maintenance data set continues to support confidence in Obefazimod's long-term safety profile.

Now I'll turn it over to Keith Fournier, our Head of Regulatory Affairs, to provide the regulatory assessment. Keith?

Thank you, Chris. So let me now turn to the feedback we received from 4 independent former FDA senior leaders who reviewed both the complete ABTECT maintenance Part 1 and Part 2 data sets. While these are independent expert opinions rather than formal FDA guidance, the feedback was remarkably consistent across 3 key areas: first, on safety and labeling, the consultants view that the overall safety profile supports advancement without major regulatory concerns. They considered it highly unlikely that a box warning would be required and did not anticipate significant additional testing or referral requirements. Importantly, they noted that potential safety considerations could be addressed through established clinical practice measures such as routine skinning examinations and standard patient counseling around sun protection.

Second, regarding dose strategy, there was strong consensus that both the 25-milligram and 50-milligram maintenance doses should be advanced. Maintaining both doses provides flexibility for physicians to tailor treatment based on individual patient needs while preserving optionality in the product label.

Third, when looking at the totality of evidence, the consultants believe that the maintenance data meaningfully strengthens the overall regulatory package. They viewed Obefazimod as having a compelling efficacy and safety profile when considering the combined Phase II and Phase III experience. They also felt that the maintenance data provide important context showing that observed adverse events remain within expected ranges and support a favorable overall benefit risk assessment.

Building on that regulatory feedback, our strategy then is to pursue a label with 50 milligrams for induction and both 25-milligram and 50-milligram for maintenance. Both the 25-milligram and 50-milligram doses deliver exceptional efficacy with best in disease endoscopic remission rates. The 50-milligram dose offers additional value for patients with more refractory severe or extensive disease, supporting our strategy to file both maintenance doses. Importantly, including both maintenance doses gives physicians the flexibility to tailor treatment based on individual patient needs.

Now I will hand it back to Marc to summarize today's presentation.

Thank you, Keith. In conclusion, we are excited to report today the remarkable efficacy of Obefazimod demonstrating in a highly refractory ulcerative colitis population. Equally important, our expanded safety database now includes more than 1,700 patient years of exposure across the Phase II and Phase III studies with patients treated for up to 7 years. The addition of the Part II data presented today, further strengthened the benefit risk profile of Obefazimod. With this in mind, we'll meet with the FDA on July 30 for our pre-NDA meeting as we continue to work towards an NDA submission by the end of this year. Looking ahead, we are very enthusiastic about the readout of the Phase IIb Crohn's program, mid '27, particularly in light of the remarkable efficacy in this highly refractory ulcerative colitis population.

With that, I'll turn the program over to Chris to introduce our 2 distinguished key opinion leaders. Chris?

Dr. Axelrad serves as an associate professor at the NYU Grossman School of Medicine and serves as the Co-Director of the Inflammatory Bowel Disease Center at NYU. Dr. Axelrad's clinical and research focus includes malignancy risk, cancer surveillance and the management of IBD patients with current or prior cancer. He will provide clinical context for interpreting the observed malignancy and NMSC findings in ABTECT relative to expected background risk in patients with ulcerative colitis.

Dr. Panaccione serves as a Professor of Medicine and Director of the Inflammatory Bowel Disease Clinic at the University of Calgary. Dr. Panaccione is an internationally recognized IBD clinical trialist with extensive experience evaluating the efficacy and safety of new therapies in ulcerative colitis and Crohn's disease. He will provide his perspective on the clinical relevance of the ABTECT maintenance Part 2 efficacy findings and the overall benefit risk profile of Obefazimod.

All right. So first, welcome to the call. I'd like to start by asking you each the same question, if you could both comment on it, that would be great. And that is, taking a step back and looking at both the safety and efficacy from the Part 2 data that we just presented, has anything changed with regards to how you view the overall benefit risk profile of Obefazimod or its potential place in the treatment paradigm? Maybe we can start with Dr. Panaccione.

Yes. Thanks, Chris, and thanks for the presentation. I guess from an efficacy standpoint, what stands out is that these were not easy to treat patients. And Part 2 did include those nonresponders in patients who had relapsed during maintenance. And those are precisely the types of patients who often challenge us in clinical practice. Yet despite that, we continue to see those meaningful rates of clinical remission endoscopic improvement and endoscopic remission in that more refractory population. And that suggests that the efficacy signal is both durable and clinically relevant beyond the original registrational data set.

I think more importantly is, in addition, if you combine this with the efficacy and the registrational data set, the proportion of patients who are benefiting from Obefazimod is amongst the highest we've ever seen in ulcerative colitis. In fact, it is the highest we've ever seen in ulcerative colitis. Having done this for over 25 years, this is the most robust efficacy data set that I've ever seen.

From a safety perspective, I think we have more than 1,700 patient years of experience across the integrated program and importantly, the safety profile remains remarkably consistent with what we've seen previously. And I think that we need to remember that the data reinforce what I think clinicians are increasingly looking for a therapy that combines deep, best-in-class -- I mean, best-in-disease efficacy with a safety profile that supports long-term use. So to succinctly answer your question, yes, it's viewed, it has changed in my view, but in a positive direction. The Part 2 data really increased my confidence in both the benefit risk profile and the potential role of Obefazimod as an important future treatment in moderate to severe ulcerative colitis.

Thank you, Dr. Panaccione. Dr. Axelrad, any additional comments on that?

Yes. Thanks, Chris. No, I agree with everything Remo said. As you know, in IBD, we're really desperate for more effective therapies, particularly for our most refractory patients. And so as underscored, this is really one of the most effective data sets we've seen and something that we're really looking forward to having access in the clinic for our sickest patients. I think what's also really important of the data set you showed is that we're still capturing a large number of delayed responders. We're still capturing patients who relapse on lower dose. And so there's already pathways to getting more patients into some of these higher remission rates that you've demonstrated. And I think that, that's really important.

As far as reflecting on the safety data, and I'm happy to talk more about that. I think that these data also really underscore very good safety. And particularly in a more refractory population where our risk tolerance changes. I feel very reassured with these data that there's not really a sacrifice of safety with a more effective drug, which we have experienced doing with other advanced and conventional therapies. So I think that this is a really nice data set and look forward to having its access in the clinic.

Thank you for that Dr. Axelrad. So maybe I'll follow up with a specific question for you on the safety. So in the new Part 2 data we presented today, we observed 2 malignancies excluding non-melanoma skin cancer, both in the 50-milligram arm. And then 4 non-melanoma skin cancers, 2 in each arm of the 25 and the 50 milligram. So based on the incidence rate and the background for the individual cases, how should investors think about this?

Yes. So I think the most important considerations here, which especially when we're talking about so few overall events is whether these exposure-adjusted incidence rates really differ from either the general IBD population or the general population of IBD patients who are exposed to other therapies. And then, of course, within the context, which you provided really nicely, the sort of the individual case characteristics that may help us contextualize some of these findings. So I think the way I really think about it is, are there red flags or are there more reassuring factors? And I think there are substantially more reassuring factors from a malignancy standpoint. I mean we're talking about very low event counts, a very common, generally experienced tumor types in the general population and in particular, the IBD population.

And then, of course, as you demonstrated in a heavily pretreated otherwise higher-risk population. And then you went through the data very nicely demonstrating there really was not an imbalance year after exposure adjustment as it compares with general data that we have from other data sets and from other Phase III programs. So I feel very confident there. Things that may make me think about a red flag, which again, just underscoring, I'm not seeing that in a handful of these cases, is that if there were high rates exceeding comparable populations or a clustering around a rare malignancy, and we're really not seeing anything like that.

And so from a cancer standpoint of which I feel really confident speaking on, there's really not something that causes concern at least from my end.

Thank you for that Dr. Axelrad. So maybe one more question for Dr. Panaccione before we turn it back over to the operator for investor questions. So today, we presented rare event data in the context of exposure-adjusted incidence rates and compared them to incidence rates from published studies to try to understand whether the overall incidence rate for patients on Obefazimod was elevated. Can you comment on whether you see this as the right methodology. So why shouldn't investors expect these rare events to balance across treatment arms versus doing the exposure adjusted analysis that we did.

Yes, I'm happy to comment on that. Maybe before I comment -- I'll make a general comment. I think first, whenever safety is discussed, the initial response is often emotional rather than analytical. And this is entirely understandable, whether you're a patient, physician or investors alike, you're naturally more sensitive to potential harms and benefits. And really, the key is to move beyond that initial reaction and evaluate the totality of the evidence through a rigorous scientific lens. And clinically, I think this is exactly the right way to look at rare events. When events are uncommon, the crude percentages can be really misleading, particularly when exposure is not balanced across the groups. And what matters is not only how many events occur, but how much time patients were actually exposed to treatment. And that is why exposure-adjusted incidence rates are so important. They allow us to take that into account by correcting for exposure.

I would also not expect rare events to balance perfectly across treatment arms in a trial of this size. By definition, those rare events occur infrequently and small numerical imbalances can happen by chance. One of the prime examples in this data set, if you go back to the registrational data set is there were 2 pregnancies, a good event when we think about IBD in the 50-milligram group, none in the 25 and none in placebo. And scientifically, we wouldn't interpret that because there's a numerical imbalance that this drug is a fertility drug or is responsible for those pregnancies. And those are the exact same numbers that we were seeing for some of the malignancies.

So it's really important to take into account. So the methodology is appropriate. And I think Jordan really summarized it beautifully is that we look for patterns. Are there events increasing over time? We can look at the Phase II? Are they above the expected background rates? Is there organ-specific clustering? None of which we see with this data set. So from my perspective, the methodology is completely appropriate and the current data support continued confidence in the overall safety profile.

Thank you so much, Dr. Panaccione and Dr. Axelrad. With that, I'm going to hand it back over to the operator.

[Operator Instructions] We will now go to the first phone question. One moment please.

Maybe before we get to the first question. We are a little bit short on time. I want to get through as many of the questions from the analysts as possible. So please one question per analyst.

Your first question comes from the line of Thomas Smith from Leerink Partners.

Congrats on this update. For the clinicians, now that we have the Part 2 maintenance data, can you just comment on how you intend to use Obe in your clinical practice? What proportion of your advanced therapy naive patients and experienced patients would you see as ideal candidates for Obe given the balance of the efficacy and safety that we've now seen across substantial data set.

I'm happy to start, Jordan, if that's okay with you.

Yes, please.

When I tend to answer this question when we have new therapies, especially with a therapy that has the efficacy that we've seen with Obe is you need to ask yourself why or where wouldn't you use Obefazimod. And so efficacy in IBD is, I always say, is always king or queen. And you can't really discount the efficacy that we've seen, especially when you look at the endoscopic remission differences compared to other existing therapies. So because the -- I don't believe that there's a safety signal here, I think that this could easily find itself as a frontline therapy in moderate to severe ulcerative colitis. But we also have the benefit that in the patient population because of drug exposure, it's shown to be very highly effective in advanced therapy exposed patients. So in that situation, it would also be a prime drug that we would use after the failure of first advanced therapy.

So I can see this being used very broadly. And if you layer on the fact that it's a once-a-day oral therapy, it's going to be a very, very attractive therapy to offer patients.

I think I'll have very little to add other than to really echo that there is very limited therapies that we have at our disposal that work in our sickest patients. And so there's really nice data presented here in a largely refractory population that this drug is very effective. And so yes, I agree with Remo that I think that there is a pathway to use in the first line and a pathway to use in our sickest most refractory patients. And that's not something that we commonly see in a data set. So I think that really could find a place in many segments of the population. And particularly refractory sick group, I think that there's a great place for this drug. But yes, I can see it being used in many segments.

The other thing that we may want to add briefly is the fact that if the drug is approved at both the 25 and 50 milligrams, it also gives that flexibility that clinicians are looking for. So you could rescue patients if you had 25 milligrams or loss of response, which is another attractive attribute of the therapy.

Great. Thank you, Remo. Thank you, Jordan. Operator, let's move to the next question.

Your next question comes from the line of Jason Butler from Citizens.

I appreciate all of the details you guys have gone into today. Again, a question for the physicians. The company has spoken to regulatory experts that suggest the malignancies and non-malignancies would not show up in meaningful warning language in the label. Do you agree with that? And to what extent would the inclusion or exclusion of that language impacts your view on how the drug will be used.

Yes. So maybe I'll take that. So I think that with a handful of very common malignancies, I don't really see that there's a clear pathway to having any sort of language around the label or restrictions. And remember that we have a lot of experience using drugs that do have labels that have concerns about adverse events and whatnot. So we already have a lot of comfort with that. So one is that at least from a malignancy standpoint of these common malignancies in a higher-risk population that don't differ from incidence rates that would be expected in the otherwise IBD population and otherwise treated IBD population. I don't really see a pathway to anything on the label.

But even if there were, I don't think that would have a major impact on our utilization, particularly from the standpoint of skin cancers, which again is the only thing really to be discussing and that's something we encounter with other drugs, and it's something that through health maintenance recommendations, our population should be receiving annual skin cancer exams anyway. So it's not really outside of our practice as it stands today.

Great. Thank you very much, Jordan. Operator, let's move to the next question.

Your next question today comes from the line of Judah Frommer from Morgan Stanley.

Thanks for the update, all the data here. Just real quick. Can you remind us what happened with the classification of the colonic dysplasia patient in Part 1? And can you help us with what role the Part 2 data play within the regulatory submission process in the pre-NDA meeting? Did that change at all? Or is this always contemplated within that package?

So maybe we'll start with Chris and then perhaps Remo or Jordan, if you want to weigh in on any of those topics around the colonic dysplasia, they probably have great perspective.

Yes. Let me just say that the company took a look at the case and realized that it wasn't a true malignancy, and we removed it from that category. It's sort of a MedDRA coding thing where it came up in the table. But yes, I'd like to invite maybe Dr. Axelrad to comment on whether or not colonic dysplasia should be categorized as malignancy or not?

Yes. So dysplasia is a colon polyp. These are precancerous lesions that are exceptionally common in the general population. That's why patients are required to have colon cancer screening and surveillance in the general population and in those with inflammatory bowel disease it's akin to a precancerous mold, for example, or it's not a cancer. It's a finding, and it's something that's completely removed and that obviously prevents the development of cancer down the line. But this is not a malignancy. It's not a cancer. It is a colon polyp that is extremely common. So really not ought to be considered a malignancy.

Great. Thank you, Jordan. And operator, let's move to the next caller.

Your next question comes from the line of Faisal Khurshid from Jefferies.

I wanted to ask, in the Phase II study that you're pulling in with the Phase III results here, was the surveillance for non-melanoma skin cancer similar to what you did in the Phase III?

Yes. Maybe, Chris, do you want to take that one?

Yes, I can take that. Yes. So it depends on when you look at the study. So for most of the study, it was different, right? So we still had the AESI for skin lesions, but not for photosensitivity. So the whole protocol and surveillance program was not applied to, I would say, the majority of the Phase II experience, but we did apply to the Phase III experience. And as you saw the number of discovered cases went up but I'd point out that even in the Phase III data set, we're still within the reference range that we provided.

Great. Thanks, Faisal. Operator, let's move to the next question.

Your next question comes from the line of Yatin Suneja from Guggenheim.

Two for me, if I may. Number one, how does FDA review the -- like what do they care more about? Do they care about NMSCs? Do they care about non-NMSCs? And especially with regard to the non-NMSCs, it seems like this is the best case scenario where you're seeing these 2 cases, they basically came from placebo and had some sort of an underlying issue. So can you maybe just confirm about these 2 particular cases for non-NMSCs -- they were at baseline?

Yes. So Chris, do you want to touch on that one and then perhaps throw it over to Jordan and Remo for their perspective.

Yes. So as I described in the presentation, some malignancies, excluding NMSCs are really evaluated differently by the agency and by clinicians because they're more serious. They have a larger impact on patients than NMSCs, which are typically resected and caught early or have a low impact on patients. In terms of the 2 malignancies, excluding NMSCs that we saw in Part 2 in the new data set, yes, I mean, as I mentioned, one of them seem to be arguably preexisting with the thrombocythemia. And the other one was a prostate cancer with only 3 months of exposure which seems to be unlikely to be related given that short-term exposure. But I think Dr. Axelrad is the expert here on this call. So maybe I can invite him to comment.

Yes. I think, of course, the FDA cares about malignancies. Nonmelanoma skin cancer is definitely low on that list. Keep in mind that, for example, nationwide SEER data does not even capture nonmelanoma skin cancers. And as far as cancers go, it's really more of an annoyance for patients when it is associated with medical treatment rather than something that is generally life-threatening or terribly concerning. Certainly, for the other malignancies that were detected here, I really think essentially nothing of them right, things like breast, prostate, these are incredibly common cancers. And it looks like based on the case characteristics that Chris provided, the patient with myeloproliferative disease really was something that predated. This is someone who had profoundly high platelet counts prior to enrollment in this trial. So I think that's, in my view, kind of completely unrelated.

And the other 2 cancers are extremely common cancers in the general population, and those didn't feel terribly imbalanced from what we see. So I really don't think there's a signal here at all and particularly from the nonmelanoma skin cancer standpoint, the FDA, certainly they care about malignancies, but that's certainly lower down on the list of something that tends to be concerning.

And specifically to the regulatory authorities, we've gone to the regulatory authorities with similar data sets in the last 4, 5 years with Phase III trials. And certainly, that has not led to any language within the prescribing information. So I would be shocked if any regulatory authority, whether it be the FDA or EMA, looks at this any differently.

And actually, just if I could follow up on 1 second is that as Remo said, we act on emotion a lot. Remember that cancer is the most concerning side effect of any drug given for anything that we do. And so of course, this is something patients care about very deeply and putting that context into something that is so rare overall, especially from these data, I think it's just really actually reassuring.

Awesome. Thank you both. Operator, let's move to the next question.

Your next question comes from the line of Julian Harrison from BTIG.

I have one for the physicians on the call. When patients now receive Obefazimod and achieve remission following induction, are you expecting a categorical recommendation for those patients to step down to 25 mg? Or is there maybe a prevailing case for some of those patients to stay on 50 mg, if there -- even if they're in remission. Can you maybe walk us through your thought process there? And do you expect that it's generalizable to other gastroenterologists.

Yes. I think that I don't see that everyone would need to step down to 25 milligrams. Certainly, we need to see more of the post-hoc analysis in things that may affect overall efficacy. I think what we tend to know from previous agents that people who've been exposed to advanced therapies made you better on higher doses during maintenance than lower doses. And so I think once we have that data, it will probably be at the clinician and the patient's discretion on whether to go on to the 25 or 50 milligrams. But as we stated before, I think that this will be driven primarily by the efficacy that you could obtain in maintenance by the 25 or 50 based on some of the baseline characteristics that the patient may have.

Right. Awesome. Thanks, Remo. Operator, we're going to take 2 more questions and then we'll throw it over to Marc for some closing remarks. And I apologize in advance to everybody who's in the queue but we will try and make time tomorrow for follow-up calls with you.

Your next question comes from the line of Sam Slutsky from LifeSci Capital.

Great work on today's update. I guess for the data in induction nonresponders who became responders with longer treatment, is there a pattern for when they typically converted to a responder? And then maybe for the 2 physicians on the line to chime in, is it possible just given that data that physicians might try to keep patients on Obefazimod longer before considering another treatment versus historical? Just kind of curious that dynamic.

All right. Chris, do you want to take the first part and then yes, over to Remo and Jordan.

Yes. It's a really good question, Sam. And we're still analyzing the data. We want to see exactly when the majority of these patients start to respond and start to feel better after week 8. And it may depend. There might be some subgroup differences. So we've got some analysis to do before we can make any conclusions there. But what we do see is remarkable efficacy at week 44. But I'll hand it over to the clinicians here to see if they have anything to add.

Jordan do you want me to take that, and you can add or do you want to take it?

Maybe I'll start with just a really quick comment that I think Remo and I asked that specific question a couple of weeks ago on the call. I mean it's an important one for context because it helps us understand when we should keep patients on drug exactly like you're suggesting versus turn away to an alternative. And we know that from other drugs that yes, if you can have people stay on drug until week 16, maybe even week 24 that with certain therapies, you can capture another proportion of response. And so that data point is going to be helpful to us clinically for sure.

Yes. And just to highlight that is we probably want to see -- it's more about trajectory. So if patients are getting better. Remember, when we design these trials, we fix the induction endpoint semi-arbitrarily, which doesn't really connect to what we do in clinical practice. So based on this Phase II data, it's very encouraging. And certainly, if you had a patient who is trending towards better but didn't respond completely as defined in the trial, you would continue that patient on therapy because we know increased time of exposure will drive patients into better outcomes as was shown in Part 2, which is quite different than somebody who has -- you have them on 8 weeks of therapy and nothing happens either symptomatically or objectively. When we look at the totality of the data set, that's why it appears that you're going to have a high response rate in these patients. So I can see patients being exposed to 16 or 24 weeks before backing off.

Great. Thank's Remo. And operator, let's go to the last question before we go over to Marc.

Your final question today comes from the line of Allison Bratzel from Piper Sandler.

I think I've heard on our prepared remarks, July 20 -- or July 30, is the date for your meeting with FDA. Could you just talk to priority for that discussion? How much you'll be willing to communicate with investors following that? If malignancies are actually going to be an issue for the agency, would it be apparent from that meeting? Or just help us understand dynamics there.

Yes. Maybe I'll throw it over to Keith, who is our Head of Regulatory.

Yes. So thank you, Pat. Thank you, Allison, for the question. So obviously, as Marc referenced in the prepared remarks, July 30 is our pre-NDA meeting with the agency and really, this is the standard stop on the way to submission, as you all well know. And we have put in front of the agency, really the outline and plan for the content of the NDA, the format, the key elements and timing when we will be submitting and with what data. So to the question about if there is a concern, would it become evident there? We are in continuous contact with the agency through our clinical studies, through our reporting, et cetera.

And just to reiterate, we have, of course, submitted all these events from our studies throughout the study periods and throughout the historic development. So we, of course, will continue to be fully transparent with them and continue to engage them in full discussions which is to bottom line at the full outline of what the NDA will contain and the questions of interest has been put in front of the FDA with the pre-NDA briefing document, and we look forward to continuing the dialogue with them.

Great. Thanks so much. And yes, operator, I think we're going to bring it over to Marc to a couple of words.

Yes. Thanks, Pat. So today's results significantly expand our long-term safety experience while demonstrating meaningful efficacy in one of the most difficult to treat patient population. So we believe the totality of the evidence strengthen our confidence on risk profile and positions us well for our planned NDA submission later this year. Thank you for your interest and good evening.

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

Good afternoon, and good evening, everyone. We hope you've had a chance to review the press release we issued after market close in the U.S. today, announcing the positive top line results of the Phase III ABTECT maintenance trial.

Joining me on today's call are our CEO, Marc de Garidel; our Chief Medical Officer, Fabio Cataldi; and our Head of Global Medical Affairs, Chris Rabbat. In a few moments, Marc will provide opening remarks, and following that, Fabio will present the top line efficacy results. Chris will then present the top line safety summary overview. Following the prepared remarks, we will open the floor for a Q&A session, where in addition to ABIVAX management, we are honored to be joined by Dr. David Rubin.

Dr. Rubin serves as the Chief of the Section of Gastroenterology, Hepatology and Nutrition and the Director of Inflammatory Bowel Diseases Center at the University of Chicago. Dr. Rubin also serves as the Chair of the International Organization for the study of inflammatory bowel diseases.

Before I hand the call over to Marc, I'd like to remind you that during today's call, we will be making forward-looking statements. A summary of these forward-looking statements are included on Slide 4 of this deck and can be referenced in our 6-K filing.

Now I'd like to hand the call over to our CEO, Marc de Garidel. Marc?

Thank you. Pat, and thank you, everyone, for joining us on today's call. Today marks an important day as we announced the landmark ABTECT maintenance clinical trial results. It is not only an exciting day for ABIVAX, but more importantly, for patients with ulcerative colitis, their family members and the health care providers that care for these patients.

Today's results firmly establish obefazimod as a potential new standard of care for the treatment of ulcerative colitis. Both the 25- and 50-milligram doses of obefazimod met the primary endpoint, demonstrated market-leading efficacy with placebo-adjusted clinical remission of 39.3% and 40.3% for the 25- and 50-milligram doses, respectively.

Additionally, both doses also met all key secondary endpoints, demonstrating robust and clinically meaningful efficacy. Importantly, obefazimod demonstrated a favorable safety profile over the 44-week period with no new safety signals identified. 580 patients were randomized in the Phase III maintenance trial, and the study achieved an incredible 10% placebo rate, the lowest reported in the Phase III UC rerandomized responder maintenance trial. This speaks to the operational excellence of the team and the study investigators.

Now I would like to hand the call over to our Chief Medical Officer, Fabio Cataldi, who will walk through the maintenance trial results in detail. Fabio?

Thank you, Marc. As a reminder, here is the overall ABTECT program design. We conducted 2 independent 8-week induction trials where active drug responders continued into a single maintenance trial. Patients that achieved clinical response to 50 milligram during induction were randomized to either remain on 50 milligram, deescalate to 25 milligram or switch to placebo. Patients that achieved clinical response to 25 milligram either stayed on 25 milligram or were switched to placebo. At the end of 44 weeks of the maintenance trial, we read out the primary endpoints of clinical remission.

These are the baseline characteristics for patients that participated in the maintenance trial. As you can see in the table, overall, the 3 cohorts are well balanced across age, induction modified-Mayo score and mean duration of disease. Maintenance patients randomized to placebo had lower induction fecal calprotectin levels as well as slightly lower corticosteroid use and maintenance baseline relative to patients randomized to 25 milligrams and 50 milligrams.

As a reminder, patients in our Phase III trial could receive oral corticosteroids only up to 50 milligrams per day and were required to begin tapering immediately upon rerandomization into the maintenance trial.

The 50-milligram cohort had a higher proportion of patients who failed prior advanced therapies at 46% compared with the 25-milligram cohort at 39% and the placebo cohort at 38%.

Finally, at the bottom of the slide, the overall completion rates are shown. The maintenance trial completion rate was approximately 80% in both the 50 milligrams and the 25-milligram scores versus only a 34% completion rate among induction responders rerandomized to placebo.

Looking at these differences in completion rates, you can already begin to see the impact of withdrawing obefazimod from patients who responded to treatment during induction.

Here, we are showing the primary endpoint of clinical remission in the maintenance trial. More than half of all patients receiving of obefazimod achieved clinical remission with 50.8% of patients in the 25-milligram arm and 40.3% in the 50-milligram arm compared with just 10.4% in the placebo arm. This translates into highly statistically significant treatment differences versus placebo of 39.3% and 40.3% for the 25-milligram and 50-milligram doses, respectively. As Marc noted, the 10.4% placebo remission rate was historically low, reflecting the high quality of the trial design and execution.

Here are the key secondary endpoints where, again, both doses achieved highly statistically significant differences versus placebo. This includes endoscopic improvement, endoscopic remission, endoscopic mucosal improvement, HEMI, corticosteroid-free clinical remission, a sustained clinical remission, which reflects the percentage of patients who achieved clinical remission at both week 8 induction and week 44 maintenance. As you can see, these are very impressive results across all endpoints, including the most objective and stringent endpoint, endoscopic remission and HEMI.

Now I'll hand it over to Chris to walk you through the safety summary.

Thank you, Fabio. Turning to the safety profile, starting at the top of the slide. Treatment-emergent adverse events occurred at a higher rate in the 50-milligram group versus placebo and at a similar rate in the 25-milligram group versus placebo. TEAEs leading to study drug discontinuation were highest in the placebo group and serious TEAEs occurred at a similar rate across the 3 groups. No deaths occurred in the trial. And serious, severe and opportunistic infections occurred at a low rate across the 3 groups, consistent with the non-immunosuppressive profile of the mechanism of action.

We observed no cases of acute pancreatitis in any group and no reports of cardiac abnormalities suggestive of cardiac fibrosis.

With regard to malignancy events, excluding non-melanoma skin cancer, in the 50-milligram group, there was 1 case of prostate cancer in a 53-year-old patient, 1 case of breast cancer in a 65-year-old patient and colonic dysplasia in a 49-year-old patient. These events occurred in different organ systems with no evidence of and all were considered unrelated by study investigators.

Looking now at non-melanoma skin cancers. In the 50-milligram group, 4 cases were observed. Two of the 4 cases were assessed by investigators as not related or unlikely to be related to treatment. Of the remaining 2 cases, 1 patient had a prior history of skin cancer. The squamous cell carcinoma case observed in a 25-milligram patient had a history of skin cancer as well as prior exposure to azathioprine, which is known to increase the risk of NMSC even after the drug is discontinued. Of note, the mean age of patients with NMSC on obefazimod was 62 years compared with 42 years in the overall study population, which is consistent with the known age-related increase in NMSC risk.

It is important to view these findings in the context of the underlying UC population. Patients with ulcerative colitis have an elevated background risk of NMSC, estimated at approximately 1 event per 100 patient years, which is why annual skin examinations are recommended in treatment guidelines. While there was a numerical difference in NMSC cases in the 50-milligram arm, importantly, the independent data monitoring committee did not consider this a safety signal. Overall, these maintenance data support a favorable safety profile, consistent with obefazimod's mechanism of action, which restores immune balance rather than broadly suppressing the immune system.

Now let's transition to discuss the rate of headache during the maintenance trial. As you may recall from our induction trials, we observed a higher rate of headache in the treatment arms versus placebo. These headaches were associated with treatment initiation, were generally short in duration and were mild to moderate in severity. In the maintenance trial, where patients had already received 8 weeks of induction treatment before randomization, we observed similar exposure-adjusted incidence rates of headache across the 3 groups. Headache also did not lead to study discontinuation in either obefazimod arm.

The time to onset of headache during maintenance does not suggest an association with ongoing drug exposure. If headaches were a recurring effect of continued treatment, we would expect them to occur in closer temporal relationship to the start of the maintenance trial. Instead, the distribution of onset of first occurrence appears random, supporting the concept that headache is primarily associated with treatment initiation early in induction rather than continued treatment in maintenance.

I'll now hand the call over to Marc to place the program results in the context of currently available therapies.

Thank you, Chris. To put the efficacy results in context, let's look at the clinical remission rates for currently available treatments. The far left of the slide shows obefazimod's new Phase III results followed by currently available oral therapies with biologics displayed on the far right. Key points of comparison are the placebo-adjusted clinical remission rates, which appear on top of the bracket for each treatment.

As you can see, obefazimod compares favorably with therapies available today. Importantly, the strong competitive profile is evident whether efficacy is assessed by placebo-adjusted treatment effect or by absolute clinical remission rates with obefazimod delivering highly competitive results on both measures.

To illustrate the strength of this efficacy in another way, this slide takes a closer look at the placebo-adjusted clinical remission results. Here, obefazimod is shown on the far left with currently available therapies grouped by mechanism of action. As you can tell, both 25-milligram and 50-milligram doses delivered placebo-adjusted clinical remission rates of approximately 40%, placing obefazimod among the highest efficacy results reported in maintenance studies to date. The only comparable results comes from the highest approved dose of a JAK inhibitor, while obefazimod substantially outperformed all S1P, IL-23s, alpha4beta7 and most JAK comparator therapies. Again, keeping in mind that this leading placebo-adjusted treatment effects were achieved alongside clinical remission rates exceeding 50%.

Finally, let's turn to endoscopic remission, one of the most clinically meaningful endpoints in ulcerative colitis. As you can see, obefazimod delivered placebo-adjusted endoscopic remission rates of 38% and 31% for the 50-milligram and 25-milligram doses, respectively. These results are clearly differentiated from every other therapy. While most therapies cluster in the 8% to 20% range, obefazimod stands alone at 31% and 38%, demonstrating a level of efficacy that is well beyond the range achieved by other treatment classes. This finding is particularly important because achieving endoscopic remission has been consistently associated with lower relapse rates and better long-term patient outcomes. Taken together with the clinical remission data we reviewed earlier, these results demonstrate that obefazimod is delivering not only strong symptomatic benefit, but also the deep and durable disease control that physicians increasingly seek for their patients.

In summary, there are 4 key takeaways from today's Phase III maintenance results. First, this was an exceptionally well-executed study, and we would like to thank the patients, investigators, study coordinators and clinical teams whose commitment made these results possible.

Second, obefazimod delivered highly compelling efficacy results. Both the 25- and 50-milligram doses achieved the primary endpoint with clinical remission rates exceeding 50% and placebo-adjusted treatment effects of approximately 40%, placing obefazimod among the top-performing therapies available today.

Third, strength of the efficacy profile extended beyond clinical remission. Obefazimod achieved best-in-class placebo-adjusted endoscopic remission rates, substantially exceeding those reported for currently available therapies and demonstrating meaningful differentiation on one of the most clinically relevant endpoints in ulcerative colitis.

Fourth, these efficacy results were achieved with a favorable safety profile through 44 weeks and are complemented by the long-term Phase IIa/IIb open-label extension data we announced in May. Notably, in that study, patients who received 50-milligram of obefazimod for 2 to 4 years and then transitioned to 25 milligram for up to an additional 3 years maintained durable clinical remission and a favorable safety profile for up to 7 years of treatment exposure.

Taken together, we believe these results validate the transformational potential of obefazimod and position us well as we advance toward our planned NDA submission in late 2026.

Before moving to Q&A, I'd like to turn the call over to Dr. David Rubin for his perspective on today's results. David?

Okay. Well, thanks, Marc, and welcome, everybody. Again, my name is David Rubin. I'm a Professor of Medicine at the University of Chicago. I also direct our Tertiary Inflammatory Bowel Disease Center here. And obviously, I work on clinical trials. I'm also the Chair of the International Organization for the study of IBD, and it's really my pleasure to address you all today. I will disclose that I am also an adviser to ABIVAX and have worked with them, although I only saw these data yesterday and, of course, have been appropriately blinded.

I want to start by saying and helping you understand, number one, that this is indeed a novel mechanism of action for patients with inflammatory bowel disease and very specific here, ulcerative colitis. And while we are coming to understand it further, the way we're thinking about it is that this is a mechanism that may provide a restoration of homeostatic balance rather than suppression of the overactive immune response. That is, I think, supported by the evidence we're seeing from both Phase II and now these very impressive Phase III results.

I have a number of comments, and then, of course, I welcome your thoughtful questions. The first thing I want to say is that this is, in fact, a very positive study, as I'm sure you can understand. But also that this was a very positive study in a group of patients with moderately to severely active UC who -- many of whom were refractory to multiple other lines of therapy. In fact, although it was a small number, this is the largest number of patients who even had been resistant to [ Janus ] kinase inhibitor therapies before they enrolled in this study. And if you look at the demographic table that was presented to you, you may have even noticed that the group that were randomized to the 50-milligram arm in maintenance actually had a more refractory population, setting the bar even higher for that group.

The delta we see over placebo is a nice way to look at the overall effect. And so on the one hand, you can emphasize that there's a very low placebo rate, which is the lowest we've seen in these types of studies. That is another way to reflect how sick these patients are and how refractory they've been. But also it sets the floor so that you understand what the ceiling is and how to interpret it. And that delta is really quite impressive. And as you already saw in the comparative lineup of other clinical trials and therapies that it exceeds all of our other therapies. The closest we have would be the Rinvoq data at 30 milligrams in maintenance. And the other way you adjust this, of course, is to go back to say, well, how many patients in those trials were resistant to 1, 2, 3 or even 4 classes of prior therapies and how refractory were they. And arguably, the data for obefazimod show that this works in the most refractory of our patients.

The other point I want to make is we didn't even look at endoscopic remission in the past. We accepted what was called endoscopic improvement, where people had Mayo endoscopic scores of 2 or 3 on entry to these studies, and we defined clinical remission as a Mayo endoscopic score of 0 or 1 collected together. When you look at a Mayo endoscopic score of 0, you have to accept that, that is essentially the bowel is completely healed and almost looks normal to us, which is why we call it endoscopic remission. And if you overlap the endoscopic remission data with the clinical remission data here, you can easily see that the majority of patients who were in clinical remission also achieved this very impressive endpoint, which, as you heard, is associated with downstream stability, which is, of course, what we want and supports indirectly that we're the mechanism that may be reinstating or sustaining homeostatic control in these patients.

And then, of course, I want to comment on safety. When you combine the safety scene in this Phase III maintenance set of data with what we've seen over the long-term follow-up in Phase II, it continues to support that there is a very nice safety profile here. There are no new signals. I will specifically comment looking for things like infection. And I do want to specifically call out that I do not think those 3 cancers that were described in colonic dysplasia, breast and prostate are related to drug nor do I think that they're related to their -- the patients otherwise. It is, of course, known that people with long-standing colitis have an increased risk for colonic dysplasia, especially people with severe colitis. So I don't find that to be worrisome in any way.

So overall, I think this is a very positive study for you all to interpret in your own ways, and I'm very happy to take questions from the group. Thank you very much.

Operator, we can now move to the question-and-answer session.

[Operator Instructions] And our first question will come from the line of Yatin Suneja from Guggenheim.

Congratulations to the transformational results. Just 2 quick ones for me. So first one for the company. Could you talk about the consistency of effect across naive and experienced patient population? What -- how would you characterize that?

And then with regard to the malignancies that you're seeing at the higher doses, could you provide a little bit more like what is the underlying or the background rate? Why are we only seeing that with the 50 because I think that's where some of the questions that we are getting from investors.

Chris, why don't you take that one?

Yes. So with regards to the ATIR, advanced treatment inactive responder yes and no data, we've held that back. We haven't released that, obviously, on the call here, and we'll be looking to present that at a future meeting. So I can't comment specifically on the maintenance results. We know that in induction, we did see a difference in those refractory patients with the higher dose versus the lower dose, and we've seen that in other treatments in this space. So I think we'll have to wait and see for the data when it comes up at a future conference.

And then your second question, Yatin.

Yes. So maybe just before we get there, I think one important, I think, element to put under context, which was, I think, already explained by David, is when you look at the malignancy and MSC rates, when you account for exposure adjustment and prior skin cancer history, obefazimod is generally in line with what we would expect to see in this ulcerative colitis patient population.

Chris, do you want to speak about specific?

Yes. So it's important to evaluate this with the totality of the evidence, right? So the observed malignancies were single events, not organ-specific and therefore, lack clustering. They occurred largely in patients with recognized risk factors, too, and were reviewed throughout the program by independent monitoring committees.

At the same time, we observed a favorable safety profile through 44 weeks in Phase III, and it's also supported by more than 440 patient years of long-term Phase II experience as well. So when we view that in the context of the total safety database, the findings observed are well within the range of what could be expected for a moderate to severely active UC population, and we remain highly confident in the overall benefit risk of obefazimod.

I'll echo that. I said it a little bit in my comments as well. This doesn't stand out to me. Patients with severe ulcerative colitis can develop dysplasia over time. That's not a surprise in any way. There's no signal. And you look back at their Phase II results, which had long-term follow-up at the 50-milligram dose even, and you don't see any signals there. So I think that this is not worrisome.

Great. Thank you, Dr. Rubin.

Our next question will come from the line of Judah Frommer from Morgan Stanley.

Congrats on the update here. Just curious about the role that you and maybe Dr. Rubin feel the 25-milligram dose could play here given the update. I would say, given the efficacy being fairly similar to where the 50-milligram is and arguably the safety being better and then also kind of rounding out with the Study 108 data and patients seeing a benefit there as well. So any initial thoughts on 25 milligram versus 50 milligram in the commercial setting?

Yes. So maybe I'll let, obviously, David respond on the side. I think when we look at the evidence, both doses demonstrated exceptional efficacy and a favorable safety profile. So we're continuing to analyze obviously the data to understand whether the meaningful difference that could exist in specific patient population. And by the way, we will report obviously more at the next congress, very likely at UET if we get accepted about more detail about that.

You will also recall that 50 milligram in the endoscopic remission was indeed better than the 25 milligram. So as of today, at least from a company standpoint, subject to see further analysis, we just got the data literally 2 days ago. Our thinking is that both doses will be very helpful for patients, and we plan to file at year-end with those 2 doses for maintenance.

So my comments on this, it's a very important question, obviously. Of course, traditionally, the agency in the U.S. has approved the lowest effective dose. But in recent years, with our IL-23 therapies and with our JAK inhibitors, they've recognized that in the ulcerative colitis space and also Crohn's that we need some dose flexibility. And in fact, there are patient populations who need the higher dose. And the mistake we made in our earlier era of therapies was when we didn't have that flexibility and we learned quickly that we were underdosing many people.

So until we have the subset analyses to give clarity on who might do best with the higher dose, we're left with understanding that the safety looks similar in both arms, which is reassuring. And our general experience overall that some people clearly need higher doses. And I do agree that there's a numerical benefit of the 50-milligram dose looking at that hard endpoint of endoscopic remission. That probably won't turn the FDA's eyes since that's not their primary endpoint there. But it's certainly of interest. And I would encourage the agency if I were advising that they approve both doses, so we have that flexibility.

Great. Thank you, Dr. Rubin.

And our next question will come from the line of Tom Smith from Leerink Partners.

Congrats on the truly amazing data here. Maybe for Dr. Rubin, just given the maintenance results here, wondering if you could elaborate a bit on how you're thinking about using obe in your clinical practice. Specifically, if you could comment on whether you're viewing this as a better agent for advanced therapy-naive patients or perhaps more refractory patients?

and then a quick question for the ABIVAX team. Just wondering if you could comment on whether this changes your outlook at all for the Crohn's data that we're expecting in the middle of next year. Obviously, very strong results here, but just wondering if this has shifted your expectations at all.

All right, Thomas, I'll start. Thank you for your question to me. And I'll say that the decision about which therapy to use for induction and maintenance requires a number of options and considerations, one of which is the presence or absence of extraintestinal manifestations, and we don't really have all that sorted yet. But then, of course, safety and efficacy and speed of onset. And here, we're certainly seeing that this therapy offers all of that and would be a reasonable drug to consider as a first-line advanced therapy if it were affordable and covered properly. And I think that, that's absolutely reasonable.

On the flip side, when you see a drug that's working in patients who have multiple lines of prior therapies with different mechanisms that didn't work and it work, it becomes the salvage therapy of interest as well. So you all know this, that the gastroenterologists who are prescribing the therapies, they fall into a bell-shaped curve of early adopters and the laggards who are waiting for more data and more experience. And I think we're going to hit it on both sides, and there'll be enthusiasm.

The narrative of the proposed mechanism is a very understandable consideration, and it has -- as an investigator and somebody who's participated in discussing this with patients, it's an easy thing to describe. So I think that, that's great. But if I had a patient, for example, with a history of plaque psoriasis as well as colitis, I'm going to lean towards an IL-23. So I think that's reasonable. And if you don't mind, I'll also comment that I fully expect this mechanism to work in Crohn's disease, and I'm enthusiastic about that study. Thank you.

Great. Maybe, Chris, do you want to add on to that?

Yes. So I think that this gives us even more confidence that the drug is going to work in Crohn's. So we're already very confident. And now when we see these results, particularly with the endoscopic remission data helps us be even stronger so.

Our next question will come from the line of Allison Bratzel from Piper Sandler.

Big congratulations from me as well. Could you just talk to how the 44-week completion rate compared to your expectations? And putting that together with the long-term Phase II data you've generated, what kind of adherence and treatment duration would you expect to see in the real world?

So we think that 82% is a very good completion rate for a trial of this design. So we're excited about that. Where we really see differentiation between the therapies that are available is in the second year of treatment. So we expect this sort of high retention or persistency rate to continue into the second year of treatment into our LTE. And that's where we will see some differentiation between our drug and some of the other drugs that have been approved.

Our next question will come from the line of Sam Slutsky from LifeSci Capital.

Congrats on the efficacy update. Two quick ones. In terms of Crohn's disease, just what have been the gating factors there in terms of enrollment and just confidence that we'll definitely get the data mid next year? And then with the cancer cases that have occurred, do you know offhand the timing that this has occurred at? And then just remind me, I don't believe there was a signal in Phase IIb. Is that correct?

Maybe we'll have Fabio take the first part of that and hand over to Chris for the second part.

Sure. So the timing update primarily reflects the increased competitive landscape in the clinical trials in Crohn's disease. At the moment, we have about 6 trials running in Phase II, 5 running in Phase III and the other in Phase IIIb. So there is really a huge competition ongoing. It's a very difficult disease to recruit historically, and I think it's just increasing the difficulty of basically recruiting patients. We are taking many measures to stay on time, maybe to even bring it in sooner than what we have announced. We are adding new geographical locations or new countries and new sites are really trying to leverage our experience with ABTECT in ulcerative colitis using some of our top recruiting sites and countries to really increase. And I think the message with the ABTECT data and the fibrosis paired with the fibrosis, I think, is going to be really a good real incentive for sites to believe even more in the drug.

I'll answer as well because I'm a clinical trial [indiscernible]. I want to explain to you that currently, for example, if you looked at the TL1As, they're trying to -- a couple of the companies are trying to recruit into Crohn's and UC simultaneously. And we don't have the Phase III results to get our arms around. So I would not underestimate the power of seeing these results in ulcerative colitis to generate enthusiasm in the investigators and potential study participants, our patients, because they're going to be excited by what they see here, and they're going to start learning more about what we think the mechanism is and what it's doing. And it's going to generate, I think, a burst of recruitment activity. So actually, I think that's a very good question given the landscape. But because of the novel mechanism, the narrative that seems to make good sense in my mind and experience and now these results, it's like -- it's going to be a burst of energy for the Crohn's recruitment. I think it's going to go well.

Chris, do you want to take the next part?

In terms of the timing of when the cases occurred, it was sort of a spattering in terms of length of exposure. There's no real consistent pattern. It seems random, which fits in with these sort of being unrelated to treatment. So that answer your question, Sam, that's what you're looking for. We're looking at like the date of when they happen.

Well, he wants to know about duration of exposure before the development of the cancer.

Yes. So there's -- I'm just looking at it here. There's no consistent pattern. It's anywhere from 49 days through 311. There's no -- and all in between.

And of course, the Phase II to answer that other part, did not show these signals at all over the long-term follow-up, there were 0.

Yes, there was 0.

Our next question will come from the line of Jason Butler from Citizens.

Congrats as well. Just one for me. Part of the trial protocol was a rerandomization of patients that were 50-milligram responders down to 25 milligram in maintenance. Anything you can say about those patients yet in terms of their maintenance of clinical remission?

Yes. We haven't released the data yet. We do have a sub-analysis of that group, which, again, we'll be looking forward to presenting at a future congress. But yes, that is an area of focus, and we're excited to show that in due time.

Our next question will come from the line of Julian Harrison from BTIG.

Let me add my congratulations on the data. First, Dr. Rubin, now that you have a comprehensive understanding of obefazimod's profile from the ABTECT trials, I'm wondering what percentage of your first, second and late-line UC patients that you envision ultimately being prescribed obefazimod?

And then I understand you believe the malignancy observations are not necessarily cause for concern. Can you maybe put those observations in context relative to other approved therapies or other approved therapies in ulcerative colitis, such as TNF and JAK inhibitors?

And then for management, on the updated guidance to Crohn's disease data, can you talk about some of the driving factors there for the update?

Okay, Julian. So for me -- and remember, I'm in a referral-based academic practice, but I do see patients almost half my time. I would consider this therapy initially to be probably 15% of my first lines, maybe 10% of my first lines, depending on the factors I mentioned earlier. I would definitely consider this to be a preferred [ third ] line in more than half of my patients based on what we're seeing here. And as we get more experience with it and as I see the subsets that you're all asking for as well, it will guide me in understanding that further.

Remember, though, I'm not in community practice, although now at this level of my career, I do have a fair number of patients sent to me earlier in their course so that I do have people who are early line choices, but that's how I would break it down.

And if you're asking me to think about the community and how they're going to do it, I think it gets back to what I said. If the drug is available and covered properly, it's oral, it offers this novel mechanism and a stable result over time with that healing of the bowel, it's a very positive message, and I think that's going to have some enthusiasm. They also have a little bit of time between them and the S1Ps and the JAKs. There was some overlap of those other drugs when they got approved and confusion among my colleagues regarding different mechanisms. So there's an opportunity here to really educate people and get things cleared up for management decisions. I'll defer to the Crohn's question perhaps to some of the folks who are from ABTECT.

Yes. Thanks, David. It's Marc. Yes, I think Fabio alluded to it, the delay linked to the Crohn's program is primarily linked to the competitive environment, which is taking place. And the reason why we are increasingly confident in our time line is due to, indeed, one, what we published in February at the ECO about the potential antifibrotic effect of obefazimod, which actually resulted in an acceleration already of recruitment. We saw that in a number of countries. But certainly now with this new very compelling efficacy in hard to treat -- including hard-to-treat patients, that would definitely accelerate the recruitment. But you have to bear in mind that, again, a year ago, this company had basically nearly no cash, and the study was basically on hold for nearly, I would say, 9 months. So we paid the price of not having cash last year, but we are picking up, and we are very confident we'll get to those time lines.

In terms of how the malignancies compare with other treatments in the space. So the overall pattern of findings we observed is well within the range of what's been reported for other advanced therapies in IBD. So that goes for STELARA, OVO, TREMFYA, Zeposia, et cetera, including the JAK inhibitors. And that just further reinforces that we think that this is sort of normal pattern that you would see in ulcerative colitis patients when you study as many patients as we did over the course of the year.

Our next question will come from the line of Sebastiaan van der Schoot from Kempen.

Congratulations on this outstanding data set. For the team, I think that prior to the maintenance results, you have a view that you would best position obefazimod in later lines. Given the results of today, how are you thinking about positioning of obefazimod in the future ulcerative colitis market?

And then for Dr. Rubin, I will be interested in your view of the use of an oral versus an injectable and whether this is a point of differentiation that truly matters in your practice.

Thanks, Sebastiaan. So in terms of the positioning, again, I'd like to remind you that more data is going to come at upcoming congresses. So you're going to get a better picture of, again, the drug's performance 25 versus 50 in different type of population. So you have to be patient on this. We will, obviously, conduct extensive market research, both with payers, but also with doctors just as we did when we had the induction results. So we'll be able to get also a better sense of with now the real data where we could be positioned. But in general, what we said is indeed probably the first few years of launch will be more in the hard-to-treat population and then expanding into first line, but pricing and access will be key. And I have next to me here, Michael Nesrallah, who is our new Chief Commercial Officer. So maybe Michael, you may want to say just one word.

Absolutely. So I'll tell you from my experience before joining the company, I was absolutely excited by the opportunity to help patients in ulcerative colitis with a transformational therapy just based on what I saw from the induction data. And based on what we're seeing now from the maintenance data, it really strengthens our results. I see an opportunity here to broaden and as Dr. Rubin said, huge opportunity to help patients in first line as well as those that are refractory, and we'll conduct some market research to sharpen our positioning over time and get a sense for where we can best position obefazimod.

Let me comment on the question regarding small molecule oral therapy compared to a monoclonal antibody protein-based therapy that's delivered as an injection or an infusion.

So this is not just about convenience. The important and unique consideration in ulcerative colitis and also in Crohn's, but for sure, ulcerative colitis, is that a moderate to severely inflamed colon leaks protein. And so, at least, in a subset of patients who don't respond to monoclonal antibodies, it's not a mechanism issue, it's an exposure issue because you leak the protein. So you basically inject or infuse and then you poop it into the toilet. Small molecules have been, in my description, a revolution for our IBD patients because of their absorption in the small bowel. They avoid that problem and you have a much more predictable PK. So aside from the fact that patients would like oral when possible and the convenience factor of that, you need to also appreciate the pharmacodynamic benefit of small molecule therapies. And because of that and as we describe this and continue to educate our colleagues, that's a specific advantage here that rheumatologists and dermatologists don't have to think about or talk about. So this is a reason why our small molecules, in general, in colitis have been so important to bring to the market, and this is no exception, obviously.

Great. Thanks, Dr. Rubin.

And next caller will be from Gregory Renza from Truist Securities.

Congratulations on the data, guys. Maybe for both the ABIVAX team and Dr. Rubin, now that we have this data set in hand, I'm curious how this helps to inform your views on the combination potential of obefazimod. What perhaps Dr. Rubin could be a rational combination partner for obe? And maybe for the company, if you could just share the latest plans on working on combinations.

Great. Thanks, Greg. Maybe we'll start with Chris, and then we'll have Dr. Rubin weigh in.

Yes. So we shared our combination strategy in the past, and I'll just reiterate here is that we think that our mechanism is so differentiated that it probably could be combined with any other MOA. For our purposes, we're most interested in combining with oral drugs to pursue a fixed-dose combination and preferably with MOAs that do not carry any sort of safety risk or labeling that we wouldn't want to inherit. And when you put things through that filter, we end up with a few of the candidates that we're running preclinical animal models on now. So namely alpha 4 beta 7, the oral, as well as the IL-23 receptor antagonist. We're also interested in PDE4. We just saw some new data at DDW on one of the PDE4 molecules, which looks impressive. And then, of course, there's also AHR, which, again, we feel is orthogonal to our mechanism and would be additive.

My comment is to say that an inflamed colon when you're inducing is different than a healed colon when you're preventing relapse. And so combo is not all or nothing. It's not combo forever. The way to think about this is in phases, perhaps more intense combination strategies for successful induction and then you leave on the safe, effective therapy and maintenance that is specific to that mechanism.

Now it remains to be proven further whether combination with obefazimod is going to do even better than we saw with the drug alone, but it's certainly reasonable to consider what Chris said. I would just say that in general, I think about a hot inflamed colon as needing general cytokine strategies to get things under control when we need them. And so the combination of something like an IL-23 that you just said, Chris, or even other options with appropriate control, anti-TNF even, but then leaving this as the maintenance or the foundational therapy that would continue in the maintenance phase. So I'm pushing for that in the other parts of what we do in our world. And I appreciate the question because that is something we'd like to understand better.

Great. Thank you, Dr. Rubin. And operator, let's move to the next question. I think we have time for 1 or 2 more.

Our next question comes from Etzer Darout from Barclays.

Congrats on the data. This is for Dr. Rubin. So beyond the clinical remission data, physicians have noted to us the importance of the magnitude of the endoscopic improvement as an endpoint, and they sort of view the 50% or better threshold as being compelling. Just wondered if you could speak to the importance of the endoscopic improvements and maybe put that into context with your ulcerative colitis patients in their experience.

Thank you. Well, endoscopic improvement refers to patients who had a Mayo endoscopic score of 3 on entry, and achieve a Mayo endoscopic score of 0 or 1. That's what endoscopic improvement means. And in the first study to actually explore this in the modern era, which included when infliximab, received its approval as REMICADE in 2005 for ulcerative colitis.

A subsequent study looked at whether there was a clinical outcome of difference in colectomy based on a Mayo score of 0 or 1. And at the time, there wasn't one, but it was a short-term follow-up with a very small number of colectomy events. So the point here, if you saw the data and you have it in front of you, was that endoscopic improvement here with the 50 milligrams was 64.1% as the secondary endpoint here and in 25 milligrams was 54.9%.

That is higher than 50%, as you mentioned, and significant and would be a very satisfactory result. And currently, it's the standard. Knowing though that endoscopic remission is achieved in 41% and 47.7% is a remarkable addition to this that we haven't seen before. And that means that those are the people who are 0. So it's really -- you can do the math.

You subtract the endoscopic improvement from the remission with a couple of exceptions, and you end up seeing that a lot of these patients got that full healing, and it's not rocket science to understand that when you're completely healed in the long term, you're less likely to have relapse loss of response and arguably, potentially downstream, even less risks of dysplasia or cancer, which we've been studying.

So you can think of all the reasons this is a good thing. It also takes one of the factors out of interpretation here because we generally accept centrally read endoscopy is superior to some of the symptoms that are based on patient recall. And so this is a very solid result, and that's how you distinguish the different ones here.

Great. Thanks, Dr. Rubin.

Our next question will come from the line of Andy Chen from Wolfe Research.

And just another question for Dr. Rubin. I think I hear you that on the physician side, there is no concern regarding the malignancies. But just curious on your speculation for how the FDA -- or how cautious the FDA would be. Do you think -- how do you think they would act? And do you think an [indiscernible] will be possible? Or is that a remote possibility here?

Thanks, Andy, for the question. Of course, the FDA is, first and foremost, looking at safety for the people and they will look at this carefully. And it remains to be seen how they choose to interpret it for subsequent labeling and ongoing evaluation. But remember that they also consider the totality of the evidence, and that includes a large Phase II trial that had similar dosing and exposure, longer exposure without signals. And so they can interpret it as they like. I don't really think a single prostate cancer or a breast cancer is going to be reflected on the drug poorly even if it happened to be at the 50-milligram dose, but I'm sure they're going to look at it.

The skin cancers, as you already heard, we see in IBD. And you do need to look at prior drug exposures, including, of course, thiopurines in those patients to know more about what else they had and what they're carrying with them and even such things these days as skin tone and risk otherwise. So there's lots of things that you can look at here, and I'm sure the FDA will do their due diligence. But I still am comfortable that they're going to be reasonable about all this. Maybe an AdCom because it's a new mechanism would be of interest. I don't know.

Great. Thanks, Dr. Rubin. And operator, it looks like we have time for about one more caller.

All right. And our last question will come from the line of Faisal Khurshid from Jefferies.

This is Anand on for Faizal. You noted 2 cases related to drug for the non-melanoma skin cancer, one of them had a medical history. Just wondering if any additional info about the second patient. And then noticed in the Crohn's trial enrollment criteria, history of non-melanoma skin cancer is an exclusion criteria, whereas it was not necessarily for ABTECT. I was just wondering if how you think about the non-melanoma skin cancer risk in Crohn's given the long-term immunosuppression there?

Chris, why don't you take that?

Yes. So for the other one, there were other confounders present in the patient other than history of skin cancer, sun exposure, age, et cetera. So even there, we think that there's reason to believe that it's due to the underlying disease and the patient's history as opposed to the treatment.

And then Fabio, maybe you could speak to the difference in the ABTECT study and the Crohn's study. Yes, relative to exclusion criteria.

Yes, of course. The differences between the APE and the Crohn's program is that the Crohn's program started after. So we were already looking for that. And in abundance of precaution, we basically excluded these patients. So that's the only reason why is that. And in reality, just to be clear, this is a history or active malignancy. So patients that have a 5-year disease-free survival are eligible. And that's pretty standard language.

Great. Thanks, Fabio. And operator, I think we'll just close with a few words.

First, I want to thank everybody for jumping on to the call today. And most importantly, thank Dr. Rubin for his time and his thoughtful input. And of course, I want to thank the patients, the investigators and the support staff for their efforts in executing the study.

With that, I wish everybody a good evening, and we'll talk to you soon.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day...

Good day, and thank you for standing by. Welcome to the ABIVAX management call to discuss late-breaking ABTECT at UEG Conference. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to your speaker today, Pat Malloy. Please go ahead.

Great. Thank you, Sandra, and good morning and good afternoon to everybody, and thank you for joining today's call to discuss the results of the late-breaking ABTECT presented at this week's UEG meeting in Berlin. Joining me on today's call are our Chief Executive Officer, Marc de Garidel; Chief Medical Officer, Fabio Cataldi; Chief Financial Officer, Didier Blondel; and Head of Medical Affairs, Chris Rabbat.

We are also fortunate to have Dr. Marla Dubinsky joining us today to provide an overview of the data presented at [ UEGW ]. Dr. Dubinsky is a Professor of Pediatrics and Medicine and Co-Director of the Susan and Leonard Feinstein IBD Clinical Center at Mount Sinai Hospital. Following Dr. Dubinsky's presentation, we'll move to a Q&A session.

Before I hand the call over to Marc to make some opening comments, I'd like to remind you that we will be making some forward-looking statements today. A summary of those forward-looking statements can be found in the slide deck.

Now I'd like to hand the call over to Marc de Garidel. Marc?

Thanks, Pat. So we are very excited to share this obefazimod data that shows its first-in-class molecule can work in induction in all type of population from naive to the most refractory population. In the next few months, we will continue to update the medical and financial community about the Phase III quality of life data, the biomarker data as well as preclinical combination data with other oral and injectable agents. We thank you for your continued interest in obefazimod, as our intent is to build a premier IBD company.

I'm going to turn our attention to Marla's presentation. Thanks, Marla.

Thank you, Marc. Thank you, everybody, and hello from Berlin, where, again, we're going to go through the ABTECT data, the Phase III program that was presented both yesterday and today, actually, and we'll review both data sets. So just as a reminder, in terms of the study design, the Phase III program you see, there were 2 induction trials and our responders in essence, would be filtered into a maintenance trial where they were rerandomized into both either the 50 or 25 milligram or placebo, which is important as we talk about today, we're going to show the week 8 data.

And Marc talked about other things that will be coming forth in terms of data. But what we're going to focus today is the types of patients that actually enrolled in this trial. Just to highlight, you can see by the green boxes, there's a reason why we're sort of highlighting and emphasizing the severity of the population. We've heard a lot about that. We've talked about even in the press release, noted that we were talking about the most refractory patient population to date just because of the timing, a lot of people had been exposed or could have been exposed to any therapies, including JAKs. And therefore, for registration Phase III induction, this is the first really looking at the severe population.

How do we as clinicians define severity? One is endoscopic severity and the first green boxes really show you the percentage of patients who had the highest endoscopy score, just as a reminder, 0 to 3. And obviously, the most severe endoscopy subscore is 3. And you could see again, you're looking at about 60% of patients overall when we pooled both the ABTECT 1 and 2.

What I do want to highlight, you can see the green box is that there was about a 10% delta between Mayo endoscopic score in ABTECT 1 and 2, just sort of looking at some subtle differences across the population as we go through the data.

Then the other green boxes are really focused on what we define second to severity is number of treatments you failed, really essentially how refractory to prior therapies have you been? And what you can see here, about 50% of patients have seen at least one advanced therapy. And therefore, you -- and then there's a group that actually received a JAK inhibitor, which is really why I wanted to highlight and note that this is the first registration trial where we're seeing this many JAK refractory, meaning failures of JAK inhibitors, which I think is very important when we think about optionality in the clinic when you have someone who today is getting what we believe to be the therapy for severe refractory ulcerative colitis, the fact that these were included, and I'll show you the data in just a minute, really as a clinician sets us up for success with our patient communication that there's hope.

Second of all, you can see 1 through 4 plus, and you can see the division of how they were divided and we'll get into clinical response across these categories of exposures in just a moment.

Let's move on to the primary outcome metric, which is at the moment, the primary endpoint, sorry, with both doses showing you pooled analysis and looking at the 25 milligram and the 50 milligram. But again, what we all look at and if you've had conversations with me before, you know I'm focused on deltas because it's not the height of the bar per se, it's really the delta between placebo and effective arms.

And what I really want to congratulate the team on is the control of the placebo rate because we know some recent press releases and what's going to be presented here at UEGW, sometimes it's hard to control for placebo rate. And what the company did by maximizing 15 milligrams, limiting certain districts, certain areas in certain countries by not overenrolling was really important for us to be able to control the placebo rate. But what you're seeing here is a delta of 16% in the 50%, I'm rounding approximately and 13% in the 25%. Next slide.

This is probably, I think, the most sort of applicable for a clinician for you all to be understanding how important this is in the clinic. Remember, on a given day, we see patients who are naive to an advanced therapy or have responded in the past that are just not on one now or they've been exposed to many, at least one. That's what happens the day a drug is approved, right? We have decision-making, and we don't want to be just deciding, oh, this drug can only be used in this population or this drug can only be used in that population as we've experienced with JAK inhibitors, for example, or even S1Ps to be fair.

So the ability to differentiate this drug really comes down to the slide and Dr. [ Gineste ] presented it today and the idea that when you look across endpoints that, yes, there is a difference in naive versus exposed, but that is every drug we have. The point being is that the more refractory you are, you really start to see better deltas between 50 and 25 actually. So that's also to note because dosing may be flexible based on where a patient is in their treatment journey, where their severity is and everyone loves dosing flexibility, just to let you know, particularly in the U.S., which is why even our IL-23s have dosing flexibility in the U.S. that they may not have in other countries.

So emphasizing that across hard endpoint, clinical remission, really understanding the deltas between and the fact that it made significance, particularly with 50 milligrams. This is a really important talking point for us as clinicians to get close to our patients who have failed every other therapy, including a JAK.

What this does also is looking at the other important endpoint, not just clinical remission, which is always the primary because a reminder everybody that clinical remission includes endo improvement as well as clinical symptoms right? So clinical remission is even a little bit of a higher bar. But the fact that you're seeing endo improvement at rates where you again see that in refractory, there's an 18% delta with for 50 milligrams in endo improvement going to a 0 or a 1 in someone who started at a 3, 60% or so started at 3, which means they had a 2-point change, possibly a 3-point change. I'm sure we'll evolve the data of Mayo 0 and 1 as we evolve over time.

But the fact that you have such significance in a very refractory patient population gives me a lot of hope when I talk to my patients about the future and where I put these drugs in my arsenal. And so when you look -- again, if you look just at clinical response because we're only focused on clinical response because just so you know, I know we're all looking at remission and endo improvement, guess what a patient cares about and what a clinician who's going to use this drug is they want to know is the patient going to be calling them in 2 weeks to tell them that they're not responding by way of symptoms. We have no endo visualization. We don't talk about endoscopy. So clinical response is really important.

And moreover, what I want you to take away from this slide is [ 011 ] looks similar. By the way, that's what S1P showed us as well. But what S1Ps didn't show us is that when you go above 1 therapy failure, there was no difference from placebo. I think it's really important that we understand the refractory nature, how this is different than S1Ps, very different in terms of refractory nature. And the good news is, as of now, you won't have to fail every biologic on the planet before you can get this drug, which is where the other small molecule, which is Rinvoq.

So it's really important that we have a good dialogue and understand the placement of this therapy and how we as clinicians on the podium because that's what really matters. What we say at an education conference helps guide treatment, but also be able to have the data to back this up. And of course, you can't talk about efficacy without talking about safety, but I do want to put the box on your radar. You see the JAK inhibitor population, right? So here, you're seeing, again, severity. And in a JAK inadequate responder, you see a delta that is -- that significant to us as clinicians, again, all looking back, I get it.

But this is what we as clinicians rely on where we're making treatment decisions. So it's important to note how we look at data in our -- when we start talking to patients about the future. All right. You can't talk about efficacy without a fair balanced safety discussion. Really, there's not much to see here, and we'll go a little bit further into the thing that everyone wants to talk about is headaches, but we'll get there in a minute.

What I wanted to show you here is across the board outside in the 50 which you see probably accounted for more by the headache difference between 25 and placebo. Otherwise, the one malignancy was prostate cancer in a male who is above the age of 50. So that, again, is not thought to be anything that is associated with OB. And so really, you're looking at across the board, very similar. And guess what we care about and what clinicians care about, serious treatment-emergent adverse events. And you could see really there's no difference between placebo and even 50 milligrams.

If we want to dive into the next slide, which goes into any AE that was at least 1% prevalence and greater than placebo. So pretty well anything that's literally like short of a scratch from stubbing my toe, it sounds like this is what you got on this table. There are no new AEs that are not on this table. So I think as you can see across the board, a hodgepodge, I'll get to the headaches in a minute, but the rest of the non-headache stuff.

What I want everyone to understand about headaches is the following. You can see that, yes, headaches are increased. Sure. We know that it was increased compared to placebo, especially in the 50. However, look at the other 2 lines under headache, meaning the second and the third. What you can see here that the average time to onset, you could see is about 1 day and so versus 7. Is that -- sorry, my glass is -- 1 day. Start on day 1 -- on day 1, so 0 to 1 in that 24-hour period is the point. So within the first 24 hours when they take OB, they will actually get a headache.

Okay. But let's look at the next line, how many actually discontinuing due to a headache. And you could see again, there's no difference across. But what I do want everyone to understand that this makes sense from a pharmacologic perspective. What happens is that is believed that the headache is really due to the parent drug. And what happens over the first 10 days and basically by day 10, there is no parent drug. Around day 2, you start to get more of the metabolite, which doesn't cross the blood-brain barrier, overlapping as the parent drug is going out. So it makes sense by day 2, that makes sense from a metabolism perspective as to the parent drug then converting over to the metabolite.

So other than that, I'll be honest, Pat, I mean I'm happy to answer questions. There really isn't something here that is different than what we see in trials. Don't meet even threshold for anything that is beyond just what we track in clinical trials, including the line.

Great. Well, thank you, Dr. Dubinsky. And operator, we can now move to the Q&A session.

[Operator Instructions] We will now take the first question. from the line of Yatin Suneja from Guggenheim.

Dr. Dubinsky, that was great. Two questions for me. First one is on positioning. I think you touched on it a little bit, but given these data, given how severe the patient population is and the efficacy across, would love to hear from you how do you envision adoption and the positioning across, I would say, the UC treatment spectrum?

And then the second one is around maintenance. Could you maybe talk about how should we think about the maintenance data? Any hint in these data that gives you comfort that the maintenance data is going to look similar to the induction or probably better?

So I'm going to take the maintenance because we don't have maintenance data, all we have is from the Phase IIb. But what I do want everyone to understand that what we're doing and what we're going into and the way we think about treatment, and we've seen it across even every drug that has come, if you have a more refractory patient, and we already started to see it in the data already at week 8, it is possible that people who have higher endo score at baseline, and we'll start to dig into the data as we start to evolve and have more data.

But endo 3, multi-refractory, we know that just based on week 8, 50 better than 25. We'll see what the maintenance is. It could be that 25 withholds anyone who went from 50 to 25 in the re-randomization. But in general, the way our mindset is, as a clinician, typically, for more severe patients, we tend to -- more is better than less. That's just the mindset we've taken with 23, we've taken with TNF. We've taken it with JAK for God's sake. That's even with the labels and the severity of side effects that people are catastrophizing around.

We say to them, you had a refractory course, you're going to need 30. And the only reason they go to 15 is if you have a side effect that you're not happy with acne, headache, whatever it will actually be. So I wanted to answer the maintenance side because maintenance is driven often by whether or not a more severe population needed to go back up to 50 if they went down to 25, that's how we evaluated Rinvoq.

I'm going to stop there because it is very similar in our mindset on maintenance decision-making. We need the data before we know whether or not 50 can be maintained on 25. If you're in deep remission at 50, you could probably stay on 25. If you're a responder but not deep remission, you may need to go to 50. It will evolve. That's how our clinical practice.

Second question about positioning, again, as I sort of hinted is that what we've been searching for is a drug that we can use first line in naive 5-ASA failure, which, by the way, what I didn't say is what is also unique about this study is 5-ASA failures were not -- they couldn't have only failed 5-ASAs. They also had to be on conventional or failed steroids, whatever the case may be, which is a unique, what we call naive population, right? So we need to already know that at baseline, we are starting with a more severe population, which we didn't talk about, but I think that's really important in Table 1 as a way to talk about severity. So for us, we thought maybe S1Ps were going to be in, I'll be honest.

Chris and I had a conversation about S1P. So he knows how my feeling is around the fact that the goal was to try and have a drug that was an oral that I can use first line, maybe in a 1 failure, but not in a 2 failure, but I had Rinvoq, right? That was sort of our mindset around small molecules. And then, of course, the idea that you need to do an AKG, a skin check, maybe an eye check within starting, no one knew, could it be before? Can I do after too complicated for a gastroenterologist who is the first line of defense who wants to give an oral but doesn't want to do a lot of work to get someone on an oral.

And for me, if all is as we evolve the story and what we've seen from Phase II and we evolve the safety and you could see it already in 8 weeks, this could fit anywhere. That's basically my take on the long term also the durability, by the way. I mean we studied every time point out to like maybe until they were 80 years old, maybe no, I'm kidding, but we are following them forever until we had this data, we were hanging on.

And so I think the durability, the fact that we were able to dose deescalate to 25 later on also gives me dosing flexibility so that if there is something that a patient that we need to reduce the dose, we know we can maintain. So I think it's really for us to take the maintenance data next, but to us as clinicians that don't represent the entire HCP community, but we are looking at this among the chitter chatting -- chit-chat amongst ourselves that this gives us a lot of flexibility on where we use these therapies in practice.

For those of us who see refractory, we're excited. For those first-line HCPs who make new diagnoses, amazing. They've been looking for a pill. I don't need to do an EKG. I think this is really a nuance that needs to be stressed.

Great. So operator, let's move to the next question.

We will now take the next question from the line of Julian Harrison from BTIG.

I have a related question on maintenance efficacy. I'm just curious if you think it's reasonable, Dr. Dubinsky, to expect a progressive trend in clinical remission rate, especially in advanced treatment inadequate responders, keeping in mind just how early maybe 8 weeks is here. And then also, I'm wondering how you think about the relative importance of induction versus maintenance efficacy when you're considering treatment options for your UC patients.

Thank you, Julian. So thanks for reminding me about the fact that every other really -- I mean, except for [indiscernible], but in the S1P and in the IL-23 world, it was a week 10 or week 12 outcome, right, 10 for ozanimod and then it was 12 for etrasimod and for all of 23.

So one thing we did see in the Phase II clinical trial program, we saw that things get better over time even. And when we chose an 8-week, obviously, you run -- you sort of endoscopy versus placebo rate. There's a lot of balance when you choose your endpoint. So here we are almost a month earlier than the current S1P and the current IL-23. So we believe, at least those of us again who are interested in this asset or thought about it or excited to see what happens next is as you follow patients, particularly refractory you need more time. I'm going to give you a historical lesson.

So with GEMINI, even vedolizumab, we look too early, 6 weeks was ridiculous, look for Crohn's patient in particular, but we learned IL-23. In Europe, for example, with miri, you could give another 12-week induction. With JAKs, the first -- with Xeljanz, the first thing that came out is refractory people need to take longer, is too early. In a refractory, you have to reinduce or give an extended induction. Same with Rinvoq for UC Crohn's, obviously, there was a safety concern about giving longer. But I can tell you, in clinical practice, many people who are refractory need more than 8 weeks to get into remission.

So I think, in general, this is not how we practice, right? We do not say, oh, you're done at 8 weeks. You're either a responder or not, particularly in a multidrug failure. So I think, Julian, the idea that we need maybe to even bake it a little bit longer in the oven, especially in a refractory, I think, will be really cool to see. Time to response will also be something everybody looks at when they're choosing induction. So we'll get that later on, which I think in a competitive UC world where time and urgency of the essence for people who are on steroids and are getting -- need to like stay on the toilet all morning because they can't get up, time to more than Crohn's is actually important. So we'll see that later on, obviously, way later on.

But Julian was asking like how do I make decision-making on drugs. And so I think for me, it's -- I can't wait to see like what happens also if you look out another 8 weeks or another 4 weeks and match it more closely to what we know as recent week 12 outcomes. And I've already commented on what makes a difference for us in maintenance, and it's all personalized to the patient severity.

Operator, we can now move to the next question.

We will now take the next question from the line of Sam Slutsky from LifeSci Capital.

Great work on the presentation. Going back to actually the kinetics of clinical response being a leading indicator for converting to clinical remission. I guess for the ABIVAX team, do you recall how likely it was for a patient to convert from clinical response and induction to clinical remission and maintenance during the Phase II study?

Yes. So yes, this is Chris. Yes, it was a little over 50% of patients that responded ended up in remission at week 48. Yes, they continue to decline from there.

Okay. And was that on top of the remission patients already?

Could you repeat that, Sam?

Yes. That 50% conversion, was that on top of patients who are already in clinical remission after induction?

Yes. Yes.

So I just want to add also what was interesting in Phase IIb is 40% of the patients who were not responding at 8 weeks did end up in remission at 1 year.

So add all together.

So -- and this is why the open-label extension, again, it was open-label extension, so some caveats to this. We ended up with 56% of the patients being in remission at 1 year, which is indeed way above where we were at 8 weeks.

100%. So that's why I think -- and especially you had a very refractory population also [indiscernible] these are naive dominant patients. So again, I think our rush to sort of not understand that severity will tell us over time that people take a little bit longer. I think hopefully, we'll show it again in the III, like what we saw in the IIb. Yes.

Sam, did you have another question?

I guess just on -- and you may have answered this, sorry if I missed this, but you that one or clinical response based on a number of prior advanced therapies. I guess just have you looked at clinical remission too or other endpoints as well as this and kind of how that look if so?

Yes. We certainly looked at it. There's just not enough room to fit all the data in one presentation. So we'll be presenting that at a later congress.

Yes. I mean, Sam is asking because the depth of the remission, can we get -- is it even more remarkable to be able to communicate to patients not just response, but there's also endo, other outcomes that we want to make decision-making just -- I noted why response is so important because that's the first thing we want to tell patients, especially refractory. But Sam is right. We've made all of our decisions on durability of these drugs based on deeper endpoints. So I think that will be important as well.

Great. Thanks, Sam. Operator, let's move to the next question.

The next question is from the line of Jason Butler from Citizens JMP.

Appreciate the detailed presentation today. I guess, Dr. Dubinsky, you talked about dose considerations in the maintenance phase. But when you think about starting this drug, can you just kind of talk us through the pushes and pulls of whether you would start a patient on 25 versus 50, given the tolerability profile and the remission data, how you think about that with the less and more advanced patients? And I guess, why would you not start all patients at the higher dose?

And then just a second question, how do you think these data translate through to the potential for the drug in Crohn's disease?

Great. So let me -- thanks for the question. The first one is really important when you say it's funny because we always say that we'll never go wrong if we use the higher dose. There's never on planning -- I mean you look at -- we don't have as much dosing optionality for induction actually. It's usually in maintenance where we have dose flexibility. There's like Rinvoq's 45. [indiscernible] is 2 milligram. It's not like I have dosing flexibility.

However, what you said is correct. We, as a community, feel more is always better, no matter what, as long as there's not a safety hit. 100% look at Rinvoq, 45 for 6, right? We went all in because we knew that you need more for refractory population. So you're right, unless headache tolerance, is different than day 1 and then gone by day 2 or 3, unless we see that differentially, that could be the only -- based on what we see today, the only reason why we would lower the dose or if someone has, I don't know, a baseline of severe migraines, would we make a -- I'm like making this up on the fly, by the way, but that's because I'm thinking about the patient tomorrow, would I ever make a decision on 25 when I see this data.

And right now, the answer would be, no, there's no need. You give more in induction, just like why combo story is why we think combo is better in induction than it is in maintenance because you want to hit them as hard as you can upfront because that makes a difference of -- if you don't get them there with induction, how do you maintain them in maintenance.

So I think you're right. I think that most of the time, it will be 50 will be where we're going to go.

[indiscernible].

I mean, listen, what I'm excited about is when you look at the MOA. So I'm not looking at the name of the drug, whether it's oral IV, the Th17 aspect today, if you look at IL-23 just for a minute to say that's within the same framework of how we impact the immune system, Th17 pathways, they're better in Crohn's than they are in [ UC ]. We can use and this -- the fact that this looks refractory in UC, I just want everyone to understand that with our 23s, we do not walk away thinking that 23 is great in refractory population for UC.

Crohn's, we can use it refractory or we can use it naive. So the fact that we are seeing a distinction here is already better than our 23 because we walk away with 23 thinking this is a naive play. This is -- I'm talking IV subcu 23 in UC. But in Crohn's, we're like whatever, bring it on. It's a great asset, and it's a great target.

So I think as we evolve the story, I think mechanistically, I would guess that it should look like other IL-23. So I'm excited to see how it evolves in Crohn's because right now, we think 23 is good for naive and refractory for Crohn's, but not for UC.

Interesting.

You learned something.

I did. All right. Thanks, Jason for your question. Operator, we can move to the next question.

The next question is from the line of Thomas Smith from Leerink Partners.

On the stellar data. First, for Dr. Dubinsky, could you just elaborate a little bit on your expectations for the maintenance data we're going to get next year? And I guess based on everything we've seen now with the Phase III induction experience, how do you expect the maintenance data to evolve relative to the Phase II? Are there reasons for thinking that it could improve or anything that you would be concerned about potential degradation, I guess, from the Phase II experience?

And then a second question, if I could, for the ABIVAX team. Could you just provide a little bit more color on the lipase increases that we were seeing at the 50-milligram dose level? I realize these were relatively low rates, but how elevated were the lipase levels? Were there any clinically relevant sequela -- and did these lead to any treatment discontinuations?

Thanks, Thomas. I'm just going to have Fabio talk to the lipase, and then I'll come back to the maintenance process.

Thank you, Marla. So if you're looking at the elevation of the pancreatic enzyme, in this case, the lipase, it's way below what we see typically in inflammatory bowel. They're more or less equivalent by group. So we feel that it's within the disease threshold, actually way below the disease threshold. We are monitoring the pancreatic enzymes, which is something we don't do typically in practice, not many physicians do that because we observe elevation of enzymes in the pancreas all the time in these patients. So it's something that we really don't do.

The important thing to note to close the -- to answer fully your question is that we don't see abdominal pain. So this elevation does not translate in acute pancreatitis. We have really just less than a handful of cases in pancreatitis, which is divided by group.

And Tom, as a follow-up, I also asked the team because not only abdominal pain, nausea, vomiting, other things, there was no pattern, meaning those are randomly irregardless of lipase levels. So we -- there's not like evidence of clinical changes that match the lipase rate bottom.

All right. So the second question on, again, when you're evaluating 8 weeks, what do you know about maintenance? I mean, again, I think the biggest question is going to be, does it get better with time? That's number one. Even people who are on 50 who dose deescalate by randomization to 25, can we maintain them? And my guess is, like every other drug that there's a certain phenotype of patients that you could deescalate after week 8 to 25 and then there's going to be a group of people who you need to stay at 50. That is a rinse and repeat for every clinical trial where we've had a rerandomized patient, particularly where you're giving them a low potential, you've got de-escalated based on randomization.

And like I said, it is usually the case that in retro, we look back and we're like, listen, Mayo endo 3, if you failed at least 2, you should be on 50 the whole way. Maybe that is different. We will see how many people needed to fall out of the 25 and go into open label for 50. That's how we knew about Rinvoq. That is exactly how we knew that someone who is refractory should stay at 30. And we don't deescalate to 15, as I noted before, unless they have acne. That is the only reason we deescalate because we know what got you to the party is what you need to stay, right, on particularly in endo 3 and refractory. And I would guess a JAK refractory patients, that's even going to be more meaningful.

So outside of being in the lack of prediction business, I would say, why would this be different? What? That would be my first question. And the only thing that's unique is the growing increase of potential people who go from responder we gave who are in remission had we extended it to week 12 or 16. That I think is going to be up for interesting investigation.

Great. Thanks, Tom. Operator, let's move to the next question.

The next question is from the line of Judah Frommer from Morgan Stanley.

Congrats on the update. Maybe one, I guess, fairly high level. Can you give us an idea of maybe improved recognition or awareness of obefazimod at this point at UEG maybe relative to prior to the top line data kind of awareness of the drug and the mechanism and how the differentiated mechanism is resonating with clinicians when compared to just the efficacy and safety data? And then maybe secondarily, any, I guess, catalyst time lines you can point us to on those additional data updates you'll be giving outside of the maintenance data over the next year?

Thank you. So I'll talk just about the enthusiasm because that's what we're in the audience. And I think, one, the [indiscernible]. So we know we ma 23s are out. We know there's somewhere down the line TL1As, and we don't have anything in between. And the idea that we're going to have an oral sooner than waiting for the next big revolution of TL1A, we need something now. So I think the excitement was around the proximity to getting the maintenance data, bringing the drug to market and having something that is oral that I can use across the spectrum of patients. And that was the sentiment after the presentation yesterday. And then when you showed the like the advanced therapy stuff, everyone is like, well, this is really exciting.

So I gave a lunch symposium today. And I could tell you that, that was a very interest -- that was a topic where people wanted to know more about this because they're like, forget 5 years from now, I want to know what -- tell me more about the way that obefazimod will be integrated into your practice. Same questions you're asking me. The audience wants to know how do the academic guys view this and where will we put it into our practice.

So that's what I can tell you on the side of the awareness here and then, of course, whatever your PR does thereafter. Marc, maybe you can comment on awareness and MOA stuff.

Yes. I mean in general, what has been, I think, fantastic for ABIVAX here is the fact that we got 2 late breakers, 2 sessions. This is extremely rare for such event. And when you heard the presentation from -- and the response to question from the top KOLs like Marla, when you hear them saying, this is incredible. This drug can work anywhere. I mean these are complements that you rarely get in the space. So you could care the enthusiasm in the room where pack, there were several hundred people in the room for ABIVAX compared to a year ago. This is a different world.

And then we met also in parallel with a number of doctors here with Fabio and the team. And I can assure you the -- whether you have been exposed to the drug or not, there is a lot of interest on obefazimod. So I think everyone is excited and looking forward to the maintenance.

But in terms of next announcement, I think the next thing on the Phase III is going to be a top line on quality of life. We have measured up to 8 different things in our PRO, including things that are very important to patients like fatigue, like bone movement in particular at night. So we are going to come up, I think, with very, very exciting data because it's important, obviously, that the medical community is excited about the compound.

But at the end of the day, the patients have to note a change in their quality of life. And I just want to remind you, this is -- these patients are diagnosed at the age of 35. In our study, they were 42 years old. So this is a working population. This is a population that has a miserable life, thanks to unfortunately to this condition.

So I think we'll deliver top line data in November. We'll release at [indiscernible]. On top of that, the richness of our Phase III will allow us to also publish more data on biomarkers for obviously [indiscernible] subsequently to DDW. And as I told you in the introduction, we want to be at ABIVAX a premier IBD company. So scientifically speaking, we are going to continue with the year of [indiscernible] and here to dominate the segment because we want to show that this drug would -- has a potential to be the reference treatment for IBD in the years to come.

Great. Thanks, Marc, and thanks, Judah, for your question. Operator, let's move to the next question.

Next question is from the line of Sebastiaan van der Schoot from Kempen.

I'm wondering whether you can talk a little bit about the growing use of advanced therapies in patients with maybe less severe disease, seeing also both presenters were suggesting positioning of obefazimod prior to advanced therapies. If so, could you maybe indicate like what type of patients with maybe less active disease you would use obefazimod for [ immunosuppress ]?

Sure. Thanks for the question, Sebastiaan. So a lot of the movement that's happening in our world is we're not quite -- we're all accepting that 5-ASAs, which are approved for mild to moderate disease, do not -- if they were tested in today's regulatory environment, may not even be approved for IBD because symptoms are not enough, right? So that was endo was the full mayo before and physician -- you're talking -- in my opinion, you're talking a different environment completely. And there are so many people that are walking around using nightly depositories because their doctor said, well, if you don't want to do these pills, I'm going to give you an IV or an injection, and they walked away saying, thank you very much. I'm not -- I'll go do my own thing. I'll change my diet and they're suffering.

And that's like [indiscernible] urgency, fecal incontinence, all the things that Marc was sort of getting at, that's a sign burden. And we are unfortunately looking at a point in time [indiscernible] people what their disease activity is. We do not take into account the burden of urgency wearing a diaper. I mean it's ridiculous. And so part of the safety fears of physicians was they didn't want to give drugs that were perceived as maybe in their own opinion were as safe as 5-ASA.

Well, if we could show that the headache rate is the same doctors of when you give Lialda, which is a 5-ASA and your patient will need to wear a diaper or use depository, you should be using this therapy. It reminds you of the safety of the 5-ASA, but has the efficacy across our portfolio.

So to me, honestly, and this is a PSA to everybody in my room and being here is to make sure that no patient is suffering necessarily when there is an oral that has a safety profile of a [indiscernible]. It is unacceptable. So hardly passionate about this question, Sebastiaan. But what I'm saying is we as a community have the responsibility of making sure people get drugs that actually feel their colon literally, not just on a commercial that says visible colon lining, but actually the burden of the disease for patients. So I think it should be applied everywhere, and that is a responsibility of all of us in this room and whoever and advocacy groups that to tell them that there's something that can help them early or late.

Now again, we're going to be approved for moderate to severe. One of the questions for the team would be, is there a mild for a later development plan, but I'm saying that we need to show that moderate, you don't have to wait until you're severe. Moderate actually straddles mild to moderate and moderate to severe. So let's focus on digging into who were the more moderate patients in the population and showing how much their lives improve.

So it is a bigger question than what you asked because our definitions are changing and our international organizations are redeveloping what is important as a target for patients, and it goes beyond what 5-ASAs have ever been able to show. So I think it's really important that the field keeps up and we start to continue to educate patients that they don't need to suffer anymore. There's no new normal you have to accept. What you have to accept is we have tools that can actually get you to work all the things that Marc was saying, you don't need to suffer.

The next question is from the line of Yale Jen from Laidlaw & Co.

Congrats on the data. Just got two here. The first one is in terms of the JAK inhibitor resistant patients, are most of those patients being treated with Rinvoq or what percentage will be treated with Rinvoq beforehand? And the second question is for Dr. Dubinsky that even we're still waiting for the maintenance data and the drugs currently have shown to be very effective in treatment-naive patients. So what was your thought or criteria for patients if you want to prescribe this drug to treatment naive or treatment without the advanced therapy patients?

Let Chris answer the JAK1 [indiscernible]. What was the dominant JAKs?

Yes. So most of the JAK failures were tofacitinib. There were a few [indiscernible], but dominantly tofacitinib.

So most were Xeljanz, very few were in both, just to give you that background on the JAK. So if I understand correctly, it was how I'm going to -- is it a dosing question you were asking for maintenance? I just want to make sure.

No, no, I'm just saying that based on the naive induction data, what kind of patient -- if you want to use it in treatment-naive patients, was there any criteria or thoughts you will put into that to make that decision?

Okay. So when we talk about treatment naive, we really talk divided into 5-ASA failures only, which is a different population than this population, which was -- they could have seen 5-ASAs, but they have to have failed steroids or immunomodulators. So this is even the next level of conventional therapy failure.

So I was just sort of going on going -- standing on my soapbox telling you that there's so many people who are seeing 5-ASA eligible only because in their minds, the patient doesn't meet the moderate criteria, which is complete nonsense, which is why I say what we view this as is for me, who doesn't -- it says conventional therapy failure. I could do whatever I believe to be conventional therapy failure. If I believe a patient needs a drug that actually has a deep remission and/or an objective endpoint and not just symptom change, I'm going to use this drug instead of a 5-ASA. That's my own clinical opinion about what -- how I will use this drug.

So as long as they're moderate to severe for people in this room from a regulatory perspective, that's what we're studying. But moderate is in the eye of the beholder. What we have to stop doing is what the regulators are asking us to do, which is define severity based on a single point in time. And so the minute my patient who may look like a Mayo 1 on endoscopy, but is wearing a diaper, do you think I'm going to say, oh, the only drug for you is 5-ASA, it doesn't -- it's illogical.

So what happens after the drug gets approved and it's on our hands the drug gets approved, we actually use it because this shows that I can use it in advanced therapy naive patients as well as even severe refractory. So to me, it gives me optionality across the spectrum of moderate to severe.

Yes. And rebounding on also Marla's thoughts, we did a market research just after the data in August. And we -- this was a U.S. only with 70 physicians. One of the -- there were 2 learnings about that market research. One is overall, there was a lot of enthusiasm from those doctors. They said 33% market share potentially in the refractory population, 15% in the naive.

But also what they said is exactly on what Marla indicated. There are some patients today who are on 5-ASA who are not necessarily doing well. But because of the current treatment landscape, physicians do not move them yet into advanced therapy. And to give you an idea, and we are going to do a more extensive market research now in the U.S. and a few European countries.

We think potentially in the U.S., this could be up to 100,000 patients in the U.S. out of the 600,000 who are on current conventional therapy. So this could expand the market considerably for obefazimod. So again, stay tuned. We're going to do market research. We'll get back to you probably by [ JPMorgan ].

Great. Thank you. Operator?

There are no further questions at this time. I would like to turn the conference back to Pat Malloy for closing remarks.

Okay. Great. Thank you, operator. Well, thank you, everybody, for joining today's call, and thank you to Dr. Dubinsky for making herself available for the call itself. Look forward to continuing to keep everybody updated. We have posted an updated corporate deck on the IR section of our website. And with that, we will close the call. Have a good day.

This concludes today's conference call. Thank you for participating. You may now disconnect.

Hello, and welcome to the ABTECT Results Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. It is now my pleasure to introduce Senior Vice President, Investor Relations, Pat Malloy.

Great. Thank you, operator, and good afternoon and good evening, everyone. I hope you've had a chance to review the press release we issued after market close in the U.S. today, announcing the positive top line results of the Phase III ABTECT induction trials.

Joining me on today's call are our Chief Executive Officer, Marc de Garidel; and our Chief Medical Officer, Dr. Fabio Cataldi. In just a few moments, Marc will provide some opening remarks. And following that, Fabio will take us through the top line results.

Following the prepared remarks, we'll move to a Q&A session, where in addition to ABIVAX's management, we are honored to be joined by Dr. David Rubin.

Dr. Rubin serves as the Chief of the Section of Gastroenterology, Hepatology and Nutrition, and the Director of the Inflammatory Bowel Disease Center at the University of Chicago.

Also, please recognize that we have only had access to this data set for a couple of days, so exhaustive secondary analysis of the data has not been completed. Also, as you will hear from both Marc and Fabio, we are preparing to submit subgroup analysis for the presentation at an upcoming International Congress, so we have held back some subgroup analysis for those purposes.

Before I hand the call over to Marc, I'd like to remind you that during today's call, we will be making forward-looking statements. A summary of the forward-looking statements are included on Slide 4 of this deck and can be referenced in our most recent 6-K filing. Now I'd like to turn the call over to our CEO, Marc de Garidel. Marc, please go ahead.

Thank you, Pat, and thank you, everyone, for joining us on today's call. Today marks an exciting day, not only for ABIVAX, but more importantly, for the patients and health care providers in the ulcerative colitis community, and we are delighted to present to you the top line results.

The ABTECT trials were truly global endeavors, enrolling 1,275 patients over 30 months across 36 countries with participation from over 600 clinical sites. The ABTECT trials included both patients who were naive to advanced therapy and those who had previously experienced an inadequate response to advanced therapy. This comprehensive approach gives us a clear picture of the therapy's effectiveness across the spectrum of disease progression.

I'd also like to highlight the fact that ABTECT is one of the largest Phase III ulcerative colitis trials ever conducted, which included the largest population of patients with inadequate response to JAK inhibitor therapy. The results of the 8-week induction trial highlight obefazimod's highly efficacious, simple and safe profile.

Finally, and perhaps most importantly, the 50-milligram dose demonstrated highly significant and clinically meaningful efficacy. We observed a pooled 16.4% placebo-corrected remission rate with no new safety signals observed throughout the trial. The statistically significant and clinically relevant outcome, coupled with a reassuring safety profile, positions this therapy as a potentially transformative option for patients. Time for Fabio to speak about the result of the trials.

Thank you, Marc. Let's start briefly with the study design. This is the overall ABTECT program consisting of two identical 8-week induction trials, starting 2 doses versus placebo, randomized 2:1:1 for 50-milligram, 25-milligram and placebo. Followed by a single 44-week maintenance trial, which is randomized 1:1:1 for 50-milligram, 25-milligram versus placebo.

I want to remind you that the endpoints for FDA and EMA were different. For FDA, the primary endpoint was clinical remission, and key secondary endpoints were endoscopic improvement, clinical response and histologic endoscopic mucosal improvement, which are referred to as HEMI moving forward. For EMA, the co-primary endpoint was endoscopic improvement and symptomatic remission. And key secondary endpoints were clinical remission, endoscopic improvement in HEMI.

We employed an innovative study design and execution element based on 3 simple but distinct pillars that we have been discussing since the beginning of the trial. First, we accelerated enrollment with clinical trial site education and expanded presence at global GI congresses. Second, we aim to minimize placebo response with the diversification of trial sites, elimination of concomitant use of immunomodulators and a lower maximum concomitant steroid dose. Third, we aim to enroll a similar patient population in Phase III as we did in Phase II in order to get similar results.

The baseline characteristics indicate a well-balanced distribution of participants with nearly 50% having prior inadequate response to advanced therapy and nearly 10% who had prior failure with a JAK inhibitor, which is the largest population of JAK failure patients in UC Phase III trials to date.

Here is the ABTECT-1 primary endpoint for FDA, which delivered high statistically significant difference in both doses relative to placebo of 21.4% and 19.3% for the 25-milligram and 50-milligram dose groups, respectively. The low placebo rate observed is a testament to the high quality of study conduct and design.

Here is the co-primary endpoint for EMA, which was met for both doses with highly statistically significant difference for symptomatic remission, endoscopic improvement. Key secondary endpoints of endoscopic improvement, HEMI and clinical response were also met with both doses with highly statistically significant p values.

In ABTECT-2, the primary endpoint for FDA of clinical remission was met for the 50-milligram dose with statistically significant difference of 13.4% relative to placebo, but was not met for the 25-milligram dose, although we do see a positive difference and a clear dose response. We will review results from the pooled population, which are positive for both doses.

Both doses met the co-primary endpoint for EMA of symptomatic remission and endoscopic improvement with highly statistical significant difference relative to placebo. The 50-milligram dose met all key secondary endpoints, including endoscopic improvement, HEMI and clinical response.

Due to testing procedures, p-values for the secondary endpoints in the 25-milligram dose are nominal. Notably, we continue to observe a clear dose response across all endpoints.

In the preplanned pooled data analysis for the FDA primary endpoint of clinical remission, we observed a clear dose response with statistically significant p-values and differences of 13.2 and 16.4 for the 25-milligram and 50-milligram doses, respectively. This clearly addresses one of the key questions from the Phase IIb regarding dose response.

We believe the clinical remission rate observed in these induction trials is very competitive, especially considering the shorter duration of the study and the number of treatments currently available. We would like to discuss a few points about the 25-milligram dose. First, as a reminder, EMA co-primary endpoint was met in both trials with highly statistically significant differences relative to placebo.

Second, the pooled analysis show a clear dose response with statistical significance for both doses. Although we have not shared baseline characteristics by treatment group at this stage, I'd like to highlight that the patient population randomized to the 25-milligram dose in ABTECT-2 was the most difficult to treat population across both ABTECT-1 and ABTECT-2 based on baseline disease characteristics. We believe this type of patient might require more than 8 weeks to achieve clinical remission as evidenced by the difference in clinical response relative to placebo.

Lastly, key secondary endpoints were met for clinical response and HEMI with statistical significance in ABTECT-1 and nominal significance in ABTECT-2.

Switching gears to safety. The final database lock will not occur until August, but is more than 95% complete. We observed an overall favorable safety profile with no new safety signals. We had low discontinuation rate due to treatment-emergent adverse events and serious TAEs, both similar to placebo. Importantly, we observed no signal for malignancy and no signal for serious, severe or opportunistic infections.

Headache was the most common TAE with lower rates of occurrence and discontinuation than observed in the Phase IIb trial. Headaches occurred at the beginning of treatment were transient and lasted a median of less than 1 week. Based on the collective clinical trial experience to date, we do not believe this will be a barrier to treatment.

Lastly, I'd like to stress, we continue to observe no safety signal indicating the need for pre-initiation testing requirements. Thank you for your attention, and now I'll pass the ball back to Marc.

Thank you, Fabio. In summary, we are very pleased to report strong Phase III induction results with our first-in-class oral miR-124 enhancer. We look forward to reporting additional analysis, including efficacy in both advanced treatment-naive and refractory patients and patients that have failed a JAK inhibitor at the future International Medical Congress.

The next significant milestone for the company is the completion of the 44-week maintenance trial, which there is no timeline risk and will be read out in Q2 of 2026.

Before we move to the Q&A, I would like to sincerely thank the patients who participated in the trials as well as the investigators and staff in approximately 600 sites in 36 countries. Without them, treatment advances like this would not be possible. Now I would like to turn the call back over to Pat.

Thank you, Marc. As we move towards the Q&A session, I'd like to remind everyone that top line data only became available to us a couple of days ago, and therefore, exhaustive secondary analysis of the data is yet to be completed. Also, as Marc pointed out, we're looking forward to presenting several subgroup analysis and complementary data sets at upcoming congresses. Before handing the call back to the operator for the Q&A session, I know that Dr. Rubin would like to say a couple of words regarding the data presented today. Dr. Rubin?

Hi, everybody. Thank you very much for letting me be here. As you heard at the introduction, I am a gastroenterologist and an inflammatory bowel disease expert at the University of Chicago, where I direct our center. And I am happy to be here to discuss these positive results and to share with you a couple of insights into the uniqueness of both the mechanism and the delivery system as well as to highlight the clinical significance of this finding for this important induction trial.

First thing I want to make sure everyone understands about obefazimod is that this is a first-in-class new mechanism for the management of moderately to severely active ulcerative colitis. We have no other therapies in our field that treat the disease the way this mechanism is believed to work. And in fact, the way I like to explain it is that rather than targeting specific active inflammation, it shuts it off at the source, resetting a balance of the immune system.

Now that may not be as important to you, but I can guarantee you that to my clinician colleagues and to our patients, it will be a very important message and something that I think will be very quickly embraced.

The second thing I want to highlight is that it is a small molecule. That means it's oral. Many of our monoclonal antibodies face a distinct challenge in ulcerative colitis because they are protein and proteins leak from active colon. That's a unique challenge we face that the dermatologists and rheumatologists do not have to deal with. So oral small molecules have a very favorable and predictable pharmacokinetic absorption and profile that avoids those challenges, and that is also a very important message about this unique therapy.

Third thing I do want to highlight is that this is a very positive study. And while it is important, as you heard, to wait for maintenance results, in general, when we see such striking and clinically and statistically significant induction results, the maintenance follow-up and if you look at their Phase II results that had long-term follow-up is something that I think is fairly predictable and will likely be equally impressive.

And lastly, of course, is understanding safety and tolerability. I think that this overall has been a very positive study from a safety point of view as well with no surprising or new concerns, and I'm very optimistic and enthusiastic about this for the people who live with ulcerative colitis and my colleagues who have to treat them. Thank you for your attention.

Great. Thank you, Dr. Rubin. And Andrew, let's proceed with the Q&A session.

[Operator Instructions] And our first question comes from the line of Allison Bratzel with Piper Sandler.

A big congratulations on this data set. Maybe just first on differences in ABTECT-1 versus 2. Could you just refresh us on differences in enrollment or baseline characteristics or geography between the 2 Phase IIIs that just might explain some of the differences across efficacy measures, just particularly for the placebo arms and the 25-mg dose group across trials?

And then just maybe bigger picture on read-through to maintenance. Could you just talk to your views on how this induction data could potentially read through to your maintenance readout in Q2 of next year as it compares to your Phase IIb experience?

Ally, thanks for your question. Good to hear from you. Maybe we'll have Fabio take that one.

Hi, Ally. So the two studies, as I said at the beginning, were two sister trials, so basically identical, very minimal differences between countries. Japan was one of the drivers.

And I think probably the most noticeable thing that we really observed in this past couple of days looking at the data when we have blinded, as I mentioned at the beginning, we have not disclosed this information, but it's the information regarding the 25-milligram group in 106 was clearly more severe than any other of the groups. And that could be maybe the reason why we see a little bit of a difference in the way that the 2 studies behave from an efficacy standpoint.

Reminder that in both studies, the 50-milligram worked right, was highly statistically significant. We met the EMA primary endpoint for both studies. So that's another good news. And of course, we are going to dive a little bit more and dissecting the data in the days to come to better understand really -- what is really -- if there is a difference between the two. We were able to keep the placebo under control in both studies. I mean it's almost unprecedented to see a 2.5 in 105, and also very, very low in 106. So clearly, they tell you that the study conduct was optimal, really an excellent execution of the trial.

And great. I think this follow-up question was a read-through to the maintenance.

Often to say always, the induction is really a prediction of what we are seeing, what we're going to see in the maintenance.

If we are looking at our maintenance data or long-term data in Phase II, right, that is still ongoing, you see really an increase in the efficacy with no impact on safety. So the safety stays really well under control in long term for what we are seeing in the Phase IIb.

And the other thing that we are expecting, which is typical what we see clinically, right, the patients with a high response, and we saw pretty high response in both studies probably will translate in remitters.

So we're probably going to see a very much higher rate of remitters in the maintenance study coming from both because the number of patients responding even in 106 in 25-milligrams is pretty high. So we're assuming to see basically to replicate probably what we have seen in the long term of the Phase IIb in the 107, which is our maintenance trial.

Our next question comes from the line of Julian Harrison with BTIG.

Congratulations on these very impressive results. First, are you able to quantitatively or qualitatively comment on the activity of obefazimod in advanced treatment experience you see? Are you seeing resilient activity in that subset consistent with studies? Second, how are you thinking about the read-through to Crohn's disease? And then finally, Dr. Rubin, I'm curious how you think the rates of headache compare to 5 ASAs in your experience?

Julian, I'll respond to the first part of the question. So as we indicated, we want to preserve the ability of the company to present at the International Congress, the split between bio-naive performance and bio-experience. However, what I would say about the bio-experience population is when you look at the combination of, let's say, clinical remission and clinical response, it gives us a lot of hope that this treatment indeed will have a great maintenance outcome for patients. So again, we'll disclose more in a few months, but it's very encouraging.

And to be sure I respond your question, you're asking what is the prediction for Crohn's based on this data?

Correct?

That was my second question, yes.

So typically, what we have observed over the years, right, that every compound, every drug that has been tested in both UC and Crohn's, typically, we see a very good effect if one indication works in the other as well, right? There's been almost every single drug studied and approved to this date. We have mainly reason to believe that the drug will work mechanistically. And we -- now that we know the doses, we believe that actually we did a good job in dosing. The study has been very well designed. It's at the beginning. So it's a bit difficult to say anything about efficacy. And obviously very, very optimistic that actually we are going to see very good results in Crohn's as well.

So I'll address the headache question, but I'm going to start by addressing the other ones as well, if that's okay. So for the experienced analysts on the call, you know that one of the challenges in managing inflammatory bowel disease and interpreting trial results is when we treat patients who have had prior treatments that didn't work or in which they were intolerant, so-called inadequate responders.

And I want to just clarify that traditionally, those were biologic inadequate responders. And I've already mentioned to you why the mechanism and delivery system of this therapy, I believe, is going to bypass some of that.

But I also want to highlight for you that we're not talking only about biologic inadequate responders with these 2 Phase III trials. It included the largest number to date of JAK inhibitor inadequate responders as well. And that's a very important point for you because as this makes its way, hopefully, to our patients, we're going to think about it in both earlier phase management as well as in patients who maybe have already been on multiple other therapies, including a JAK inhibitor. And this therapy worked well in those more resistant patients and still had statistical significance in those breakdown subanalyses. So I think that, that's very positive to understand.

My second comment about whether this may work equally well in Crohn's. Of course, we need to show that and Crohn's studies have some additional complexity. But in terms of the mechanism, there's no reason not to think it's going to work in Crohn's as well. There's nothing unique about the active immune system in UC or in Crohn's of the colon, especially and of the ilium as well that would make us think this isn't going to be something we should be actively pursuing and expect some nice results as well.

The headache is a unique point that I'm glad you brought up. It was in a small number of people, smaller than we saw with the earlier phase studies and was not durable. It lasts for a short period of time in the first few days or week of treatment and goes away. We don't see that with 5-ASA in answer to your question. But I don't anticipate that this is a therapy that's going to replace aminosalicylate in ulcerative colitis. This is a therapy that if everything goes as we hope and anticipate, would be positioned after aminosalicylates and earlier in the treatment algorithm before getting to injectable or infusible therapies. So I hope that addresses it for you. I was specifically interested in that and was pleased to see these results in that regard.

And our next question comes from the line of Thomas Smith with Leerink Partners.

Congrats on the really stellar data here. Maybe just for Dr. Rubin, I was wondering if you could just expand on your comments and how you're thinking about the induction results here relative to some of the other oral treatment options. How important is the prospect of being able to start Obe without specifically screening for ocular or cardiac issues? And can you just talk about what proportion of your moderate to advanced UC patients you think would be an ideal candidate for a drug with Obe's profile here?

Yes. So thank you for the question. I would start by just reminding the group that the S1P receptor modulators, ozanimod and etrasimod that have been available now for some time for moderate to severe UC have unfortunately carried the concern by folks that there can be cardiac arrhythmias or macular edema. And that's been somewhat misinterpreted, but sometimes perception is reality. It has to do with an asymptomatic self-limited sinus bradycardia with those S1Ps. And the S1P mechanism does have a rare event of macular edema. So that's led to people being hesitant to use them, even though they're very good treatment options and safe otherwise.

The JAK inhibitors, I'm sure that most here are familiar with the concerns as well as the fact that they had been labeled to be used after anti-TNF in the U.S. due in part to the concern about major adverse cardiovascular events and venous thromboembolic events that occurred in a Phase IV rheumatoid arthritis safety study in high-risk patients.

So this therapy does not have either of those concerns. And what I have advised the company and have been discussing is that, as my colleagues in the GI world are learning about small molecules, they need to help them understand the differences in mechanism and not lump them all together. And I think that they're going to be able to do that well and that this is going to have a clean signal when it comes to those prior concerns. We don't have to worry about that. And we want to distinguish this mechanism as unique but also safe.

Got it. That is super helpful. And maybe just a question for the company, if I could. I know you're still going through some of the subgroup analyses, but I was just wondering if you could comment either quantitatively or qualitatively about some of the differences in efficacy from a regional basis.

Was the efficacy in the North American subgroup consistent with the overall top line results? And were there -- was there any one specific region, I guess, that was driving the treatment effect there?

Thanks, Tom. Good to hear from you. Maybe we'll have Chris Rabbat, Head of Medical Affairs, take that one.

Yes. So the data is really fresh. We're still analyzing it. And today, we've shared the relevant top line data, and we'll have further disclosures at upcoming medical conferences, including looking at regional sub-analysis, but good question.

Got it. That makes sense. If I could just sneak in one last follow-up, if I could. Just -- I know you've generated some initial data in combination with an S1P. Can you just talk about how you're thinking about potential combination strategies now that you have these really strong Phase III induction data and a really clean safety profile?

So yes, Tom, maybe we'll have Marc take that, just how we're thinking about the combination given this -- the profile of the drug that we're seeing right now.

Yes. So we all know and Dr. Rubin can actually speak better about that than I can do that the future of ulcerative colitis treatment may also involve a combination therapy, just like what happened in oncology.

So 2 years ago, when we basically built our strategic plan, we really wanted to address this challenge upfront. So we are in the process of testing a number of compounds in preclinical experiments. We have to indicate that, however, those experiments are a bit hard to conduct because the technicalities of finding the right models where each individual drug works and then you can obviously test the combination is somewhat difficult given the history of some of the compounds.

But I would say more recently, we have turned our attention to obviously two compounds or that could be of interest. One of them is obviously the IL-23, which has gained obviously some momentum with our Phase IIb. And also, we are looking at the alpha4beta7. So we hope that by the end of this year, we'll be able to report preclinical outcome of this combination.

Our next question comes from the line of Sam Slutsky with LifeSci Capital.

Congrats on these great results. Got two for Dr. Rubin. I guess just one interpreting clinical trial data in ulcerative colitis. Could you just talk about the relevance of induction data versus maintenance for determining how you might think about when to use a treatment like obefazimod?

And then this next one, maybe you answered a little bit, but just as you think about new patient starts versus switches, kind of where might obefazimod play into that whole scheme based on its unique profile?

Thanks for the question, Sam. So I'll start with just thinking about induction versus maintenance. The traditional teaching and trial design that was essentially developed because of biological therapies and the absence of other options was that whatever worked in induction, we would continue into maintenance, both because the mechanism was working, the so-called sequential monotherapy approach and because we didn't really have much else.

And in biological therapies with anti-TNFs, we early on learned that if you tried using it intermittently or episodically, patients developed immunity to the drug and had hypersensitivity reactions.

With small molecules, we can challenge that assertion in that approach and think about whether a therapy could be used for induction only and then transition to something else in maintenance.

But in general, that is predicated on two things. Number one is the safety and maintenance, which is always the long-term safety considerations. And number two, it's based on understanding what else you can use with it or what you would transition to.

The idea that we can induce with a single therapy, withdraw it and then treat the patient with something else is of great interest. We do that with steroids, for example, but it's not proven. And it would be a paradigm shift in thinking about how to do these types of treatments. So the clinical trial designs are just like you see here and even the ongoing other trials similarly pursue induction and maintenance. And as you all appreciate, I'm sure, committing to maintenance therapy is also where there's more money to be made in the long term.

So that's another incentive for industry to develop these types of trials. But frankly, that's okay if it's working and again, if it's safe. Safety becomes more important when you're in stable maintenance of remission.

In regards to the second question you had, which was about where we would position it, I believe, I would say to you that it's going to be the usual story, which is that people use what they know. There are the early adopters, and then there are the people who are stuck because other treatments aren't working and they're going to throw this on as the caboose on their train of options that they've tried for a patient.

So I think it's going to remain to be seen. Whenever there's a new molecule and a new mechanism, there's a lot of the usual challenges that we face in educating people. But when you have results that are this strong, it doesn't take that long for somebody to treat one or two patients. And when that translates to their clinical practice, they become believers and then they start using it more.

So I think that we can predict that if this does what we hope in maintenance, that that's going to be the story. There will be a little bit of a lag as people learn about it, some of those who are hesitant and want to see longer-term follow-up, but we do have the Phase II long-term follow-up to lean on for now. And then you'll see people starting to adopt this as a easier drug to use and something that they want to position early in their management strategies. I hope that gets to it. I know it's a little bit of a long answer for you.

Yes. I guess just for a quick follow-up. In terms of the maintenance while we await those data, obviously, the Phase II data were strong. I guess if that's replicated, how big of a deal is that the magnitude of benefit they showed in maintenance for Phase II in terms of, again, thinking of how it might be used in practice?

Well, you can understand even if you don't have colitis and don't treat people with colitis that a once-a-day oral therapy that has a favorable safety profile and a very stable disease control would be a very attractive maintenance option.

Even if you look at mesalamine, our old standby that we use for milder disease, those patients in maintenance are on usually 2 or 4 pills a day, large pills because of how it's delivered. If you think about even our safest biological strategies, IL-23s and vedolizumab, ETYVIO, we have to rely on injections or infusions. So there is something very compelling about this. And obviously, we want to be thoughtful about what we can expect with maintenance, but I think that this will deliver something that people are anxious to have and then we'll have the opportunity to learn more about it as we move forward.

Great. Thank you, Dr. Rubin. And I know we have a few more in the queue for questions, and I want to be respectful of Dr. Rubin's time. So if you can hold your questions to just one so we can get through everybody. Operator, could we go to the next caller.

Our next question comes from the line of Jason Butler with Citizens JMP.

Let me add my congratulations on the results. Just in terms of the 2 doses, was there any hierarchical analysis included in the statistical analysis plan between the 2 doses? And given the strength of the overall data set, do you plan on pursuing approval for both doses?

Yes, this is Chris. Yes, so there was hierarchical. I know you guys have been asking that question for months now, and now I can tell you that we did test the 50-milligram dose first and all key secondary endpoints on the 50-milligram after that, and then we moved to the 25-milligram and then key secondaries after the 25-milligram. So that's for the FDA testing strategy.

And we hit both primary and all key secondaries with the 50-milligram in both trials. As you know, 25-milligram hit primary and key secondary in one trial for FDA. In the other trial, it missed on the primary for FDA, but it hit on the co-primary for EMA. So we think both doses are viable. We think both doses are important. And once you see additional data, you'll see why we think that both of these doses should be taken forward.

Great. And then if I could just squeeze in a real quick follow-up. Do you have a final at least rough estimate of enrollment in the maintenance study?

Yes. The study is fully enrolled for maintenance. So the patients are ongoing in the study, and we are on target, as we say, for midyear next year for end of results.

End of next year.

I mean I'm obviously not on the advisory committee for the FDA, and we're not at that stage yet. So I'll just make a general comment, which is that the FDA over the last number of years, with our available JAK inhibitors is a good example, but also our IL-23s that have been approved in the IBD space, have adopted the phased approach of understanding that more intense therapy seems to be better in induction, but dose flexibility is available in maintenance so that people can identify the lowest effective dose.

So we'll see what maintenance looks like, but I think that these results are strong regardless of how you decide to slice them. I would just predict that perhaps the FDA is going to be interested in making sure we don't underdose in the induction interpretations anyway.

And maybe if I can just add and perhaps clarify. So the maintenance data is on track to read out in Q2 2026, and we had 678 patients that moved on or that were eligible to go into the maintenance study.

I always say the best predictor of maintenance is successful induction. And that's my clinical message and my teaching. So I expect the same in a trial.

And our next question comes from the line of Judah Frommer with Morgan Stanley.

Let me add my congratulations to the results here. Maybe just kind of more of a planning question. Just curious how you're thinking about further funding the company with these results in hand. I'd imagine there were several scenarios you had kind of kicking around internally, but kind of funding through the maintenance trial versus kind of the combo trials that you've talked about. Any color you can provide on that front?

Hi, Judah, Didier Blondel, CFO speaking. So yes, we're still on the same line. So of course, we know we need to raise money in the short term. Our cash runway goes into Q4. Of course, we're refining our plans. So what we want to do at minimum is to be able to fund the company until the management has a read out Q2 2026 plus a bit of a buffer. And here, we're talking about around $200 million. So the rest, we'll see.

Our next question comes from the line of Yatin Suneja with Guggenheim.

Let me add my congratulations as well. And I apologize if you addressed this question earlier because I got dropped twice. So the question is on between the 50-milligram and the 25-milligram dose. So did you prospectively -- or how is the hierarchy? Was the 50-milligram predefined as the first analysis that you do?

If you have already answered that, the next question is, can you maybe help us understand what your expectation would be for effect in naive versus experience? Should we maintain -- should we expect a similar delta being maintained because generally the placebo tends to be lower for experience. So just curious how you are articulating. And maybe final question, if I squeeze in. How transient were the headaches?

Chris, do you want to take that?

Yes. Yatin, so we did answer the hierarchical question just a moment ago, and there was a hierarchy. We tested the 50-milligram first for FDA for both trials. It was positive in both trials. And for EMA, it was a co-primary and both trials were positive on both doses.

The second question, we have not disclosed that yet. We are holding some data back for some presentations at upcoming medical conferences. So I won't comment further on that.

The headaches were transient. You'll see on the slide deck that was presented. The median duration was actually less than 1 week across the board. So we do not believe that these headaches are going to be limiting for the uptake of the therapy.

Our next question comes from the line of Sebastiaan van der Schoot with Van Lanschot Kempen.

Congrats on the stellar data set. Really great execution. I was wondering whether, Dr. Rubin, maybe you could talk a little bit about the treatment adherence that we saw in the previous studies and how you will put that into context. And then I was wondering for the company, whether they could already give some qualitative statements regarding treatment adherence in the maintenance part of the Phase III study, whether you can say something qualitative about that.

So the question is about adherence. And whenever you have a patient self-administering their therapy and they're feeling well, it's a natural tendency to potentially skip doses or be nonadherent. It's a well-described phenomenon in our field. It's something we educate about to remind people that if they're in remission and they skip a dose of their medicine, they will still be in remission. That's the point of remission. But it will accumulate over time, the more that happens and then they'll have a much higher risk of relapse. So it does require education.

It also will require some better understanding later about the durability of effect if people have an interruption in treatment. All of those things are real-world considerations that we have to deal with right now with our JAK inhibitors, our S1Ps, our 5-ASAs and frankly, with our injectables. So I hear you. This is always an issue with chronic conditions. It does require education and additional information and other ways to monitor people so that we know they're taking their meds, and that's all part of a future plan, I would hope and expect.

So it's a good question, but I can't say more than that right now. In a clinical trial, of course, we're counting pills and we know what people are doing. Or we think we do, I should say.

Our next question comes from the line of Yale Jen with Laidlaw & Company.

My congratulations as well. Just two quick ones. The first one is that you guys mentioned that 25-mg and 50-mg you move forward. More specific question is that, do you anticipate both move forward to United States as well as in Europe or one or two might be -- or any differences?

Then the second question here is that in terms of this drug, given the current data, although still need to see the maintenance outcome, what percentage of patients, at least in your practice or in your understanding might immediately be benefit from this drug at this moment?

So to answer the first question, yes, we are planning as we stand today to elaborate and consider bringing both doses for approval according to the data set for induction. Of course, we need to see what happened in the maintenance. From a safety standpoint, there was a question before. The safety continues to stay very similar to what we have seen in induction in maintenance in a branded fashion.

Regarding the subpopulation, I think you were asking about that. It seems like the -- both doses of the drug works in both sides of the disease. So for both severe patients and naive. Again, we have not disclosed more information on that, but that's our preliminary answer to that question.

Thank you. I'll now hand the call back over to CEO, Marc de Garidel, for any closing remarks.

Yes. Thank you, operator. So as a conclusion, I would like to highlight that those results give us a lot of hope for patients with ulcerative colitis, but we still have to reach the next stage, which is a maintenance study. And as indicated before, this will be in Q2 of 2026.

And finally, I'd like to thank all the ABIVAX team for the fantastic execution work done also with [ IQVIA ]. 1,270 patients, 30 months to recruit. Outstanding placebo results, execution, which was challenged, I think, a few months ago. I think this team deserves a lot of credit. So thanks to them, and obviously, thanks to all the participants in the trial. Thank you very much.

Ladies and gentlemen, this does conclude today's...

And before we close, operator, I just want to thank Dr. Rubin for making himself available for today's call. I'm sure the audience found it quite valuable. And so I just didn't want to let the call go without doing that.

Thank you. Ladies and gentlemen, thank you for participating. This does conclude today's program, and you may now disconnect.