Good day, and thank you for standing by. Welcome to the Abivax ABTECT Part 2 Results Webcast and Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question during the session, you will need to press star one and one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one and one again. 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. 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 data set, 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 will 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 four of this deck and can be referenced in our 6-K filing.
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 strengthen the overall profile of obefazimod in ulcerative colitis. These efficacy data reinforce the meaningful clinical benefits of obefazimod, even in a 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 for 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 de-risks 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.
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's 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 non-responders. In fact, 37.2% of 60 mg induction non-responders 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 mg 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 dosed escalated to 50 mg in Part 2. Second, the extended safety database gives us even greater confidence in the overall safety profile of obefazimod.
We are now accumulating more than 1,700 patient years of exposure across phase II and phase III. When these data are viewed in context, malignancy and non-melanoma skin cancer incidence remain within or below the expected background rates for patients with ulcerative colitis. We have also carefully evaluated individual safety events and found no evidence of a new or unexpected safety pattern. Importantly, these findings are consistent with obefazimod's unique mechanism of action. By enhancing miR-124, obefazimod helps 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 available today, they do not expect a box warning for obefazimod.
They support filing both the 25 mg and 50 mg maintenance doses to address the needs of different UC patient populations, and believe obefazimod has a clear regulatory path forward. 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 four key design features. First, Part 2 serves as a supplemental data set to the Part 1 registration of cohorts, shown on the left-hand side of the slide. Second, Part 2 includes two distinct patient populations. Part 1 relapser, who were rescued with open-label obefazimod 50 mg, and induction non-responders, who either continued their assigned obefazimod dose, or if previously on placebo, were randomized to an active dose. Together, the two 50 mg 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 conferences. This slide highlights that Part 2 patients were a more difficult to treat population. Over 55% had previously failed at least one advanced therapy, compared with approximately 38%-46% in Part 1. Despite this, 44-week completion rates remain high, ranging from about 70%-86% across the Part 2 groups. This context is important when interpreting the efficacy results because clinical benefit in induction non-responder and relapser represent a higher bar than a traditional maintenance population. It is also important to recognize that induction non-responders that entered Part 2 had only been treated for eight weeks without achieving clinical response. This means they are carrying a substantially higher inflammatory burden at the start of maintenance treatment than induction responders that entered Part 1.
This is reflected in 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 entered Part 1. While over 80% of induction responders in Part 2 have fecal calprotectin levels above the clinically meaningful threshold of 150 mcg/g , 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%-22% of the prior advanced therapy patients failed a JAK inhibitor in Part 1 and Part 2, respectively. Now, let's focus on the Part 2 induction of responders. These are patients who had not achieved clinical response after eight weeks, but continued obefazimod treatment.
This see-through design allowed us to evaluate whether longer-term therapy would provide benefit in patients who would discontinue in other phase III programs. It did not allow drug non-responders to enter maintenance or long-term expansion. By week 44 on maintenance, efficacy was observed across all exploratory endpoints, with numerically stronger results seen in the 50 mg 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 analyses are exploratory and uncontrolled, the consistency across symptomatic and objective endpoints suggest that a meaningful proportion of initial non-responders benefit from continued obefazimod treatment.
The second population we will discuss consists of patients who initially responded to obefazimod during treatment and were randomized to 25 mg in Part 1 of the maintenance study, but subsequently relapsed and received open-label rescue treatment with a higher 50 mg dose. Importantly, 45.5% of these patients who relapsed on 25 mg 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 physicians 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 mg- 50 mg can reestablish disease control in a meaningful proportion of patients. In early June, we reported that obefazimod delivered potential lasting disease endoscopic remission among induction responders.
Data show that this efficacy extends to an even more challenging population Patient will not respond after initially weeks induction period. Remarkably, the endoscopic remission rates achieving this induction non-responder 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, 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. 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 1st data release. Next, we'll review the Part 2 safety data with 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 area. 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. 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 for all approved UC treatments since Entyvio was approved in 2014. In ABTECT maintenance Part 1, there were two events, or 0.52%, placing obefazimod in the middle of the range. Both events occurred in the 50 mg arm with no events in the 25 mg 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 two 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 the 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 mg group accounted for 288 of the 420 patient years of exposure, or nearly 70%, with approximately 30% for the 25 mg, and notably, as a reminder, zero 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 mg 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 groups. TEAEs leading to study discontinuation were somewhat higher in the 25 mg group, which was partially driven by worsening of ulcerative colitis. One death occurred in the 25 mg group and was assessed by the investigator as unrelated to treatment. The suspected cause was pulmonary embolism in a patient over 65 with multiple preexisting 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 two malignancies excluding NMSCs. Both deemed unrelated to treatment by study investigators in patients with preexisting 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 mg dose in Part 2, both cases landed in the 50 mg group. NMSCs were balanced by event count, with two 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 year 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 mg 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 mg 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 in a broad UC population, including both treatment-naïve 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 three 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 three 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 three 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 two 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/uL , which remained elevated throughout the study until the diagnosis. The second case was a 55+ year-old patient diagnosed with prostate cancer who was exposed to obefazimod for just three 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 three 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 non-clinical 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 in ABTECT, with no treatment imbalance. I'll detail this on the next slide. NMSCs remained 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 six 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 mg, and 10.0 with 50 mg. 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 slide applies the same exposure-adjusted approach to NMSCs across the three 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 three 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 incidence was 0.59 per 100 patient years, which is slightly below the published UC reference range of 0.7- 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 four NMSCs reported, two for each dose. All four cases occurred in patients with multiple established risk factors, including three with advanced age, three with prior thiopurine use, two with prior history of skin cancer, and three with failure of multiple advanced therapies with an established increased risk for NMSCs.
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. I'll turn it over to Keith Fournier, our Head of Regulatory Affairs, to provide the regulatory assessment. Keith?
Thank you, Chris. Let me now turn to the feedback we received from four 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 three key areas. First, on safety and labeling, the consultants viewed 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 skin examinations and standard patient counseling around sun protection. Second, regarding dose strategy, there was strong consensus that both the 25 mg and 50 mg 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 believed 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 is to pursue a label with 50 mg for induction and both 25 mg and 50 mgs for maintenance. Both the 25 mg and 50 mg doses deliver exceptional efficacy with best-in-disease endoscopic remission rates.
The 50 mg 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. 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, demonstrated 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 seven years. The addition of the Part 2 data presented today further strengthen the benefit-risk profile of obefazimod. With this in mind, we'll meet with the FDA on July 30th for our pre-NDA meeting as we continue to work toward an NDA submission by the end of this year. Looking ahead, we are very enthusiastic about the readout of the phase II-B Crohn's program in mid 2027. Particularly in light of the remarkable efficacy in this highly refractory ulcerative colitis population. With that, I turn the program over to Chris to introduce our two 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, 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. That is to, 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.
Yeah. Thanks, Chris, thanks for the presentation. I guess from an efficacy standpoint, what stands out is that these were not easy-to-treat patients, Part 2 did include those non-responders in patients who had relapsed during maintenance. Those are precisely the types of patients who often challenge us in clinical practice. Despite that, we continue to see those meaningful rates of clinical remission, endoscopic improvement, and endoscopic remission in that more refractory population. 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 in 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. Importantly, the safety profile remains remarkably consistent with what we've seen previously. 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. To succinctly answer your question, yes, it has changed 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?
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. As was 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, there's already pathways to getting more patients into some of these higher remission rates that you demonstrated. I think that that's really important. As far as reflecting on the safety data, I'm happy to talk more about that, I think that these data also really underscore very good safety.
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 experience doing with other advanced and conventional therapies. 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. Maybe I'll follow up with a specific question for you on safety. In the new Part 2 data we presented today, we observed two malignancies, excluding non-melanoma skin cancer, both in the 50 mg arm, and then four non-melanoma skin cancers, two in each arm of the 25 mg and the 50 mg. Based on the incidence rate and the background for the individual cases, how should investors think about this?
Yeah. I think the most important considerations here, 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. Of course, within that context, which you provided really nicely, are sort of the individual case characteristics that may help us contextualize some of these findings. I think the way I really think about it is, are there red flags or are there more reassuring factors? I think there are substantially more reassuring factors from a malignancy standpoint. I mean, we're talking about very low event counts of very common, generally experienced tumor types in the general population and in particular, the IBD population. Of course, as you demonstrated in a heavily pretreated, otherwise higher-risk population.
You went through the data very nicely demonstrating there really was not an imbalance here after exposure adjustment as it compares with general data that we have from other data sets and from other phase III programs. 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, we're really not seeing anything like that. 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. Maybe one more question for Dr. Panaccione before we turn it back over to the operator for investor questions. 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? Why shouldn't investors expect these rare events to balance across treatment arms versus doing the exposure-adjusted analysis that we did?
Yeah, 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. This is entirely understandable, whether you're patient, physician, or investors alike. You're naturally more sensitive to potential harms than benefits. Really, the key is to move beyond that initial reaction and evaluate the totality of the evidence through a rigorous scientific lens. 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. What matters is not only how many events occur, but how much time patients were actually exposed to treatment. 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 two pregnancies, a good event when we think about IBD in the 50 mg group, none in the 25 mg and none in placebo. 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. Those are the exact same numbers that we were seeing for some of the malignancies.
It's really important to take into account, the methodology is appropriate, 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. 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.
Thank you. To ask a question by the telephone, please press star one and one on your telephone keypad and wait for your name to be announced. To withdraw your question, please press star one and one again. 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. Please, one question per analyst.
Thank you. Your first question comes from the line of Thomas Smith from Leerink Partners. Please go ahead.
Hey, guys. Good afternoon. Congrats on this update and thanks so much for taking our questions. For the clinicians, now that we have the Part two maintenance data, can you just comment on how you intend to use obefazimod in your clinical practice? What proportion of your advanced therapy naive patients and experienced patients would you see as ideal candidates for obefazimod? Given the balance of the efficacy and safety that we've now seen across substantial data set? Thanks so much.
I'm happy to start, Jordan, if that's okay with you.
Yeah. 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 obefazimod , is you need to ask yourself why or where wouldn't you use obefazimod? Efficacy in IBD, 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. Because I don't believe that there's a safety signal here, I think that this could easily find itself as a first-line therapy in moderate to severe ulcerative colitis. 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.
In that situation, it would also be a prime drug that we would use after the failure of a first advanced therapy. 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's very limited therapies that we have at our disposal that work in our sickest patients. There's really nice data presented here in a largely refractory population that this drug is very effective. Yeah, 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. I think that really could find a place in many segments of the population and in a particularly refractory sick group, I think that there's a great place for this drug. 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 mg and 50 mg, it also gives that flexibility that clinicians are looking for. You could rescue patients if you had 25 mg or lost response, which is another attractive attribute of the therapy.
Great. Thank you, Remo. Thank you, Jordan. Operator, let's move to the next question.
Thank you. Your next question comes from the line of Jason Butler from Citizens. Please go ahead.
Hi. Thanks for taking the question, and appreciate all of the details you guys have gone into today. Again, a question for the physicians. The company's 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 impact your view on how the drug would be used? Thank you.
Yeah. Maybe I'll take that. 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. Remember that we have a lot of experience using drugs that do have labels that have concerns about adverse events and whatnot. We already have a lot of comfort with that. 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.
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. 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. 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.
Thank you. Our next question today comes from the line of Judah Frommer from Morgan Stanley. Please go ahead.
Yeah. Hi, guys. Thanks for the update, all the data here, and thanks for taking the question. Just real quick, can you remind us what happened with the classification of the colonic dysplasia patient in Part 1? Can you help us with what role the Part 2 data play within the regulatory submission process and the pre-NDA meeting? Did that change at all, or was this always contemplated within that package? Thanks.
Maybe, we'll start with Chris, and then perhaps, Remo or Jordan, if they want to weigh in on any of those topics around the colonic dysplasias. They probably have great perspectives.
Yeah. Let me just say that the company took a look at the case and realized that it wasn't a true malignancy. We removed it from that category. It's sort of a MedDRA coding thing where it came up in the table. Yeah, I'd like to invite maybe Dr. Axelrad to comment on whether or not colonic dysplasia should be categorized as malignancy or not.
Dysplasia is a colon polyp. These are precancerous lesions that are exceptionally common in the general population. That is why patients are required to have colon cancer screening and surveillance in the general population and in those with inflammatory bowel disease. It is akin to a precancerous mole, for example. It is not a cancer. It is a finding, and it is something that is completely removed and that obviously prevents the development of cancer down the line. This is not a malignancy. It is not a cancer. It is a colon polyp that is extremely common. It really not ought to be considered a malignancy.
Great. Thank you, Jordan. Operator, let us move to the next caller.
Thank you. Our next question comes from the line of Faisal Khurshid from Jefferies. Please go ahead.
Hey, guys. Thank you for taking the question. Wanted to ask, in the phase II study that you are pooling 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?
Yeah, I can take that. Yeah. It depends on when you look at the study. For most of the study, it was different, right? We still had the AESI for skin lesions, but not for photosensitivity. The whole protocol and surveillance program was not applied to, I would say, to the majority of the phase II experience. We did apply it to the phase III experience. As you saw, the number of discovered cases went up. I'd point out that even in the phase III dataset, we're still within the reference range that we provided.
Great. Thanks, Faisal.
Great.
Operator, let's move to the next question.
Thank you. Your next question comes from the line of Yatin Suneja from Guggenheim. Please go ahead.
Hey, guys. Thank you for taking my question. Two for me, if I may. Number one, how does FDA view what do they care more about? Do they care about NMSCs? Do they care about non-NMSCs? Especially with regard to the non-NMSCs, it seems like this is a best case scenario where you're seeing these two cases. They basically came from placebo and had some sort of an underlying issue. Can you maybe just confirm about these two particular cases for non-NMSCs? They were at baseline? Thanks.
Yeah. Chris, do you want to touch on that one and then perhaps throw it over to Jordan and Remo for their perspective?
As I described in the presentation, 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 two malignancies excluding NMSCs that we saw in Part 2 in the new dataset. As I mentioned, one of them seems to be arguably preexisting with the thrombocythemia. The other one was a prostate cancer with only three months of exposure, which seems to be unlikely to be related given that short-term exposure. I think Dr. Axelrad is the expert here on this call, so maybe I can invite him to comment.
I think, of course, the FDA cares about malignancies. Non-melanoma skin cancer is definitely low on that list. Keep in mind that, for example, nationwide SEER data does not even capture non-melanoma skin cancers. 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. 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. I think that's, in my view, kind of completely unrelated.
The other two cancers are extremely common cancers in the general population, those didn't feel terribly imbalanced from what we see. I really don't think there's a signal here at all, particularly from the non-melanoma skin cancer standpoint, the FDA, certainly they care about malignancies, that's certainly lower down on the list of something that tends to be concerning.
Great. Thanks. Oh, go on. Sorry.
Specifically to the regulatory authorities, we've gone to the regulatory authorities with similar data sets in the last four or five years with phase III trials. Certainly that has not led to any language within the prescribing information. I would be shocked if any regulatory authority, whether it be the FDA or EMA looks at this any differently.
Great.
Actually, just if I could hop in one 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. Of course, this is something patients care about very deeply. Putting that context into something that is so rare overall, especially from these data, I think is just really actually reassuring.
Awesome. Thank you both. Operator, let's move to the next question.
Thank you. Your next question comes from the line of Julian Harrison from BTIG. Please go ahead.
Hi, thank you for taking the question. 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 they're in remission? Can you maybe walk us through your thought process there, and would you expect that it's generalizable to other gastroenterologists?
Yeah, I think that I don't see that everyone would need to step down to 25 mg. 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 may do better on higher doses during maintenance than lower doses. I think once we have that data, it'll probably be at the clinician and the patient's discretion on whether to go on to the 25 mg or 50 mg. As we did it before, I think that this will be driven primarily by the efficacy that you could obtain in maintenance by the 25 mg or 50 mg based on some of the baseline characteristics that the patient may have.
Great. Awesome. Thanks, Remo. Operator, we're going to take two more questions, then we'll throw it over to Marc for some closing remarks. I apologize in advance to everybody who's in the queue. We will try and make time tomorrow for follow-up calls with you.
Thank you. Your next question comes from the line of Sam Slutsky from LifeSci Capital. Please go ahead.
Thanks for taking the question, great one from today's update. I guess for the data in induction non-responders who became responders with longer treatment, is there a pattern for when they typically converted to a responder? Maybe for the two 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 for historical? Kind of curious that dynamic.
All right, Chris, you want to take the first part. I guess over to Remo and Jordan.
It's a really good question, Sam, 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 eight. It may depend, there might be some subgroup differences. We've got some analysis to do before we can make any conclusions there. What we do see is remarkable efficacy at week 44. I'll hand it over to the clinicians here to see if they have anything to add.
Jordan, 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 a call. I mean, it's an important one for context because it helps us understand when we should keep patients on drug, exactly as you're suggesting, versus turn away to an alternative. We know that from other drugs that, yes, if you can have people stay on drug till week 16, maybe even week 24, that with certain therapies, you can capture another portion of response. That data point is going to be helpful to us clinically for sure.
Yeah, just to highlight that is, we probably want to see that it's more about trajectory, so if patients are getting better. Remember when we designed these trials, we fixed the induction at endpoint semi-arbitrarily, which doesn't really connect to what we do in clinical practice. 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 eight 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. I can see patients being exposed to 16 weeks or 24 weeks before backing off.
Great. Thank you both. Operator, let's go to the last question before we go over to Marc.
Thank you. Your final question today comes from the line of Allison Bratzel from Piper Sandler. Please go ahead.
Hey, good afternoon. Thanks for fitting me in. I think I heard on the prepared remarks July 30th 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? Just help us understand dynamics there. Thank you.
Yeah. Maybe I'll throw it over to Keith, who's our Head of Regulatory.
Yeah. Thank you, Pat. Thank you, Allison, for the question. Obviously as Marc referenced in the prepared remarks, July 30th is our pre-NDA meeting with the agency. Really this is the standard stop on the way to submission, as you all well know. We have put in front of the agency really the outline and plan. The contents of the NDA, the format, the key elements, and timing, when we will be submitting, and with what data. To the question about if the concern would become evident there, we are in continuous contact with the agency through our clinical studies, through our reporting, et cetera. Just to reiterate, we have, of course, submitted all the events from our studies throughout the study periods, and throughout the history of development.
We, of course, will continue to be fully transparent with them, and continue to engage them in full discussions. Just to bottom line it, the full outline of what the NDA will contain, excuse me, 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. Yeah, Operator, I think we're going to bring it over to Marc to say a couple words.
Yeah. Thanks, Pat. Today's results significantly expand our long-term safety experience while demonstrating meaningful efficacy in one of the most difficult to treat UC populations. We believe the totality of the evidence strengthens our confidence in obefazimod's benefit 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. Thanks for participating. You may now disconnect.