AgomAb Therapeutics NV (AGMB) Earnings Call Transcript & Summary

Good morning, everyone, and welcome to the Agomab Therapeutics Virtual management and KOL event. [Operator Instructions] As a reminder, this webinar is being recorded, and a replay will be made available on the Agomab website following the conclusion of the event. Before we begin, we would like to remind everyone that today's presentation contains forward-looking statements. These statements are subject to risks and uncertainties that may cause actual results to differ materially. Please refer to Agamab's SEC filings for a discussion of these risks. I'd now like to turn the call over to Tim onerous, Chief Executive Officer at Agomag Therapeutics. Please go ahead, Tim.

Thank you so much, Sarah, and thank you all for joining today's webcast to discuss the open-label extension results of the Phase IIa STERNOVA study in patients with fibrosinosin Crohn's disease. Let me introduce our speakers for today. Very glad we are joined by Dr. Reeder from the Cleveland Clinic, who is also Chair of the Star consortium. On the company side, I'm joined by Chief Medical Officer, Flip Bissell; and Chief Financial Officer, Pierre Kaul. I'm Tim ones, and thank you so much for joining today. Today, we'd like to spend a little bit of time on background to educate on the fibrosinosin Crohn's disease, but soon thereafter, would like to dive straight into the Senova Part B, which is the open-label extension study of the Phase IIa. Thereafter, we will spend sufficient time on next steps and potential Q&A. At Okuma, we focus on fibro-inflammatory indications, and our clinical pipeline consists of assets. The lead compound, ontinisatib, is a gut-restricted ALK5 inhibitor in development for patients with fibrosinosin Crohn's disease. Earlier, we reported on the positive results of Part A of the STANOVAstudy with a favorable safety profile and intriguing signals on endoscopy and radiological parameters. Today, we're absolutely thrilled to discuss the open-label extension part. The second asset in development is a longer strict ALK5 inhibitor, which targets the same pathway, the transforming growth factor pathway, but is a distinct compound from the lead asset. The second asset is an inhaled small molecule designed to penetrate the plan. Recently, we reported on the positive Phase Ib data in a smoke hort of patients with idiopathic pulmonary fibrosis. For today, however, we will focus on the lead compound on initiative. Crohn's disease is a fibroinflammatory indication, where progression of disease is driven by both inflammation and fibrosis. Whilst the inflammatory part is recently well addressed by the currently approved therapies, Turner is simply not designed to address the fibrotic part of the disease. As a result, Crohn's patients over time develop fibrotic strictures and develop towards surgery. This is why we target the TGF pathway via an ALK5 inhibitor to develop a direct antifibrotic drug. Our aim is to offer patients a first pharmacological treatment option for patients with fibrosinosin Crohn's disease. So let's zoom in on fibrosing Crohn's disease. Fibrosis leads to expansion of the exceller matrix, thickening of the bowel, stricter formation and narrowing of the intestine, especially in the terminal ileum. As a result of the narrowing or obstruction, patients develop symptoms, especially pain after meal, they apply extensive coping mechanisms, for example, changing their diet, splitting their meals or meshing or blending their food. But over time, symptoms worse than most patients progress towards surgery despite being on anti-inflammatory background treatment. Parbosinosin Crohn's disease is therefore considered the highest unmet medical need in inflammatory bowel diseases. And these difficult-to-treat patients are not a small subgroup of patients. Actually, 46% of all Crohn's patients have fibrosinosin chronic disease. And this is a group that also drives IBD-related health care costs with significantly more procedures and hospital visits that the patient -- than the patients without strictures. What these patients really want is indicated in the middle can. They want to live a normal life without severe symptoms, especially pain. They want to eat normally with a higher quality of life. But most importantly, they want to avoid further progression of disease, especially towards surgery. And to achieve this, what we need to develop is a pharmacological approach that directly targets the fibrotic drivers of disease progression, probably with a compound that is safe, convenient to use and compatible with current standard of care. This has been the starting point of optimist. And this is also the reason why we're so excited with the over-label extension data that we present today. But trebling a new field and today is yet another incredibly important step in that journey. With that, I would like to hand it over to my colleague. Philippe the honor of presenting the data is yours.

Thanks, Tim, and hello, everyone. It is my pleasure to present the results of the Steven label study. And the reminder, Senova was a Phase IIa study designed to assess the safety and pharmacokinetics of antirust in patients with Crohn's disease and symptomatic structures. Patients were required to have well-characterized Iliastructurs according to contract criteria developed by the Stainsortium. Patients were also required to have obstructive symptoms at baseline as defined by the minimus core 2 for the severity domain of the SPR questionnaire. The Taste included Part A, which was a double-blind placebo-controlled study, where patients were allowed to continue their backound of care and then receive either placebo, a low dose once a day or high dose tied. Patients received de drug for weeks, after which they were invited to enter a pole extension, during which all patients receive twice a day for an additional weeks. DA was initiated once we obtained positive interim results in Part A, at which time roughly half or the patients have completed the study and were not eligible for the ore, of those who are eligible, 94% accepted, enter early. This results in the 4 patients, which are part of this analysis. The primary objective of DLA was to assess the extended safety profile of not -- this was not trivial since we are targeting the TGF-beta pathway, which is a major pilomorpic pathway, demonstrating a favorable safety profile for up to 60 weeks was, therefore, our key objective. The second objective was to assess whether the efficient gut-restricted profile of antinicotib was maintained after extended treatment. Besides these primary and security objectives, we plan to explore efficacy signals focused on the incidence of surgery, aldoscopic binarization, strict hematology assets by radiology and patient-reported outcomes. Here, I'd like to highlight the limitations of DOA, primarily the lack of a placebo control, but also relatively small sapsize. We believe that we see in treating signals, but we should take these results with caution. Let's start with patient disposition. As indicated, 4 patients entered the open-label extension. A total of 37 patients were able to complete the additional 48 weeks of treatment, reaching up to 60 weeks of treatment for patients already receiving anticatab in Part A. While patients dropped out. This defines 25% in the part rate, which is what 1 will expect for year to the period. There was no specific pattern in terms of cost or timing for these discontinuations. Of note, only of the 12 discontinuations occurred in patients already receiving the high dose in Part A. So we did not see a higher incidence of discontinuations in patients with the longest exposure at the highest dose. First, wanted to make sure that the population entered the Opel extension was similar to the overall Senova population at baseline to ensure that there was no selection bias. This was -- this is what we show here based on baseline demographics and disease characteristics as we see the 2 populations are very similar. Patients have a long study of con disease, averaging 15 to 17 years. All patients have ill disease, either isolated or elocoloic disease. We know that patients with our disease tend to be refractory to treatment. Approximately 40% of patients had at least 1 prior structure resection surgery highlighting disease severity in these patients as well as the recurrent nature of industrial structures. It's also important to keep in mind that prior sectorization surgery is known to be the most important predictor of further structure reaction side. Importantly, 75% of patients were a stable dose of antipartbiologics. These background treatments seem to work well because the luminal impactor burden was relatively low with an average CDI around 150, meaning that roughly 50% of patients were in clinical remission and mostly mild disease activity at the start of the study. CRP was low as well, confirming the low level of inflamed burden. High-rates patients at symptomatic structure despite relatively good cultural information. This is in line with the evidence showing that antibater treatments have limited efficacy on structures, if any. As far the safety profile, intercity, starting with the serious adverse events. During the AA, a total of 5 SAEs were reported in 4 patients. These patients included a patient who presented with 2 SAs perforated abilities and small bowel obstruction. A patient with close is worsening a patient with a risk structure and the patient with kidney stone. Overall, a low incident services without pattern Arkansas. Beyond SAEs, we assessed the more gel safety profile of intensity during the open-label extension, looking at adverse events to understand whether we would see any new signal or changes in the intensity, nature or severity of adverse events up to 60 weeks of treatment. This was not the case. No septic signal was detected, looking at AEs, we also proactively assess specific signals, including color injury inflammatory effect or science of vasculitis based on signals reported for systemic limiters or signals which may be related to TTR inhibition. So did not detect signals there. The 2 organs that the active parent molecules are the gut and the liver, we did not detect any signs of drug-induced liver injury with no elevations in liver and times. There was also no increase or change in the nature or intensity of GI advanced events of an extended treatment period. Furthermore, we did not detect any safety signal when reviewing the lab results, physical examination or ECG recordings. Importantly, the DSMB indicated after each and bind data review meeting that they had not identified safety signals and had no conscience. They recommended every time that the study continues as per protocol. We can conclude that oral untrust continues to show favorable safety profile with no safety glass detected after extended treatment. This favorable city profile can be readily understood when looking at the PK profile, Antti remains efficiently got restricted with very low systemic exposure. We are looking here at the exposure profile based on SPAPKdata collected in both A and B of the study. At the very bottom, we see the levels of antisatib in plasma at steady state, showing very low levels in both parts A and B, which are super in both here. Average levels are very far from the IC, as you can see. We also see the profile for the inactive metabolite, MT5, which is generated in the liver once untreatabort. We see the profiles in light and dark gray corresponding to Part A and Part B. These profiles are almost superimposed indicating that the gut restructure mechanism is maintained over time. In conclusion, the study met its primary and security objectives, demonstrating a sustained favorable safety profile and efficient pet-restricted PK profile over up to 60 weeks of heat. Beyond the primary and secondary objective of the study, we explored potential efficacy signals during extended treatment with entrust 20-milligram twice a day. Keeping in mind the limitation of an open label study, we believe that we see intriguing signals. Let's start with the event rate, which is an endpoint based on hard clinical outcomes. Even Trade is defined as the occurrence of surgery or endoscopic balloon dilation. The event rate was calculated for patients receiving 12 milligrams twice a day during Part A and/or B. The Cat Americas was enva is shown here on the single endoscopic balloon dilation which supported and locate the stricter resection surgery. While they are not far directly contare placebo-controlled trials in this population, there are 3 recently published retrospective studies by the stock consortium that help us provide some context for the very low event rate observed in tinea. The same including protease used to define stricter severity, namely the constrict criteria developed by the stock consortia. The capital layer cut published for these reference studies for a highly -- a significantly higher incidence events compared to no. Here, we showed how these Kaplan may clouds translate into event rates, 3% for Senova compared to the analyzed EBrades of 26% and 35% reported in the reference studies, while again, we should be cautious with the comparing trials, inventory reporting for Cnova is clearly significantly below these publish studies. It is also important to remember that patients included in the state of a trial presented multiple risk factors for events, including ELL disease for all patients, epistructure resection strictures approximately 40% of patients obstructive symptoms in all patients at baseline as well as severe structures meeting the construct criteria and which include features known to be associated with surgery. It is very important to see a reduction in the event rate for several reasons. First, it is very meaningful for patients because the factors driving surgery or balindalation are to a great extent what defines a disease bad and this include sustained or worsening symptoms concerts, invasive or burdens and imaging procedures and eventually hospitalization, surgery or EDD. These are all things that patients would like to avoid. Events are also important to regulators, a reduction in the event rate could potentially constitute a robust registration end point. And finally, it is important to pay us because these events are a key driver of health care costs. Peters for patients with structuring disease amount to ATM per year compared to patients with uncomplicated care disease, and these pore primarily related to increased consults, imaging, hospiciation, surgery and BD. Altogether, the low event rate is an encouraging finding and would be a key letup for our upcoming Phase IIb trial. I would like to now turn to aging. Here, we should be cautious not to over interpret the data, not only because it lacks the placebo controlled, but also because we have limited information about what changes are quickly meaningful. Let go through the MRE data, which was used to assess strict term apology. We are presenting 3 MRE barometers that we already presented for the placebo-controlled Part A of the state of our study and which have been previously published has been clinically meaningful leading to a stricter length, power thickness and the diameter of the associated preset dilation. Here, we show changes from baseline in millimeters, each graph shows changes in Part A, where patients receive different treatments, including placebo or one of the intercity doses and then changes during the open-label extension, where all patients were switched to Tata. In the graphs, the black dot line shows the average change for all patients included in the Ole and showing a general trend for Orlaco. We also included lines according to our patients received in Part A because it is interesting to observe MRA changes once patients switching from placebo to the high dose of anticitib. As reported previously, patients in placebo tended to worsen from stricter length and bialthickness in Part A, during the OLA when patients are antirust, these patients stop worsening. In fact, they tend to stabilize and catch up with the patients already on entrectinPartA. Overall, when looking at the profile for all patients, so the black line, we see trends of improvement for bowel thickness and maximum diameter of the prestabilization. For stricture length, the diastole significant viability and less consistent profile, especially with. We explore the reasons for this variability and identify changes in patients with short structures are the main source of variability. Here, we show the same 3 parameters in patients with short structures on the left and with launch pictures on the right. The cutoff is 5 centimeters, which is generally used to qualify short structures. Not only data sets, 2/3 of the patients had longer structure, so greater than 5 centimeters. We clearly see that in patients with thatetures, shown on the left, there is mostly noise with significant variability and inconsistent profiles. In contrast, underwrite, in patients with longer structures, we see what looks like clinical data with limited variability and coherent profiles. On this slide, we zoom on the 2/3 of patients with longer structures, we now see even more clearly that for all 3 parameters, patients on placebo were not doing as well as patients receiving entity bring Part A. Once they switch to the high dose in the OLA, they stop worsing and tend to catch up with patients previously on enticed. On structure lent, we see great live variability and a pattern which indicates radiological stabilization over time. The switch effect for all -- seen for all 3 parameters is very suggestive of a drug effect in DRA. We think that the MR results are very encouraging, especially given the consistent trends for stabilization and improvement over time across the 3 different parameters. This positive MRE data in keeping with the low Entre. Felasco, we entry do not have sufficient data sets to draw meaningful conclusion. Ensco was option at we 48 and the vast majority of patients declined the procedure while dropped out. As shown here, there were 79 patients with on basaltictures and these are the patients where we wanted to assess long-term passive. This group of patients was reduced to only 13 patients are 48, results obtaining 13 patients in a novelistudy providing sufficient information to draw the conclusion in the 13 patients or homelescopy was available 4, 2 had a passable structure and 11 had non-passing structures. This data is anecdotical and enroll 2 additional patients with passable or on path structures could ease to see the pitas positive or negative and it would be likely missed either way. We prefer to rely a bit obtain on endoscopic possibility in the larger sample size and placebo-controlled part A of the study, which showed substantially higher passivity rates in the 200-milligram twice a day arm compared to the placebo of the loads. Let's move on to the patient reported outcome measures. Here, Alinta provided a consistent trend on the different parameters, which were assessed. This include obstructive symptoms with this pro on the left, or disease activity with a SEDAR in the middle and quality of life with short IBD question as on the right. We see a consistent reduction in symptoms and an increase in quality of life already doing part. A significant placebo effect have been observed, although faster and potentially larger effect was suggested for the high dose of onsite -- what is striking, however, that patients continue to improve over time to reach a minimal symptoms at 48. This is particularly interesting as we also have a 97%, but 97% of patients are Kitaremission as we for compared to about 50% at baseline achieving and mating climation at this level is notable and can be linked to the low event trade in redigitabilization. I will now kindly ask Dr. Fran Reeder to provide an overview of these comp results on the next slide.

Thank you very much, Philippe, and thank you so much for having me on the call. had the opportunity to review the Sonova open-label extension data prior to this call and put together my key takeaways on this slide is the directing a co-PI of the Star Consortium. So overall, I'm very positive about these results. And most importantly, they are generally favorable long-term safety and tolerability profile of the drug is the new mechanism of action and with a broad pathway inhibition, and this was very favorable long-term safety data. the gut-restricted PK profile was confirmed in the open-label extension. And what stood out to me is a very impressive low annualized efficiency-related event rate of only 3%. So I'm not aware of any data set in existing structures using the constrict criteria that after 1 year of follow-up had only 1 endoscopic balloon dilation that sample size for a total event rate of 3%. This was very impressive. As of the other endpoints and all of these potential efficacy-related endpoints have to be interpreted with caution, but I'm still optimistic about them. There were signs of sustained disease control. What stood out to me there was a very low symptom burden at week 48 which again includes the classical obstructive symptoms that are food related. It includes the classical Crohn's disease symptom scale, the CDAI and then increasing quality of life of the IBD and this is, again, impressive because all these patients started with all the existing small bowel strictures. When looking at the longer structures longer than 5 centimeters, there's overall stabilization of structure length. And the best comparator here, and we can talk more about that in the Q&A is an example of pulmonary fibrosis where regression of fibrosis is not what is being achieved. In fact, there is a prevention of decline and this trial showed even better. There was a stabilization of structure length and the trend towards improvement in wall thickness and then the dynamic outcome of prestricted dilation, which suggests an increased possibility of the structures with the reduced prestructurination. So overall, the results, in my opinion, support for the development of enteritisinosin Crohn's disease and what is called the Overa study and then potentially even an expansion to other additional IBD indications, and I will be available later for Q&A. Back to you, Philip.

Thanks, Flora. It's actually a meeting to take the last slide and then we will hand over to Q&A. So what's next is to run the Nobera Phase IIb trial, which is indeed a placebo-controlled dose range finding study that is considerably longer, 52 weeks versus 12 weeks placebo-controlled into. Importantly, we will even use a higher top dose of 400 mg BID given the favorable safety profiles we have received to date. And we embed more patients up to 32 fibrosing trans patients, so 80 per arm. We will further test and validate the different endpoints. For the primary endpoint, we will look at possibility as measured by endoscopy, for which we saw a 32% response rate on patients on 200 mg BID in the placebo-controlled part of Nova. Additionally, we will look at events like EBD and surgery. We will look at radiological parameters as measured by MR and a new version of the patient-reported outcome and other quality of life assessments. Today's data, we cannot wait to get started, and we very much look forward to continue to work with investigators, regulators and the large IPD community to bring a first pharmacological treatment to patients with fibrosinosin Crohn's disease. Looking towards the future, with the recent IPO in February, we have a current cash position of $280 million, and we're very well financed to progress both the ontoinitiative franchise and the IPF program. With this, we are now ready for the Q&A session. Sarah the floor is yours.

Great. Thank you, Tim. Yes. So at this time, we'll be conducting a question-and-answer session with our speakers to our analysts joining us live. [Operator Instructions] So please hold for a brief moment while we poll for questions. So our first question comes from Judah Frommer at Morgan Stanley.

Yes. Congrats on the data, and thanks for providing this webcast. It was very informative. I guess our key question is, in terms of learnings for a potential pivotal trial, what can you take away from the data you've shared today? I guess, particularly on event rate. Is there a way to sort of marry that functional endpoint to maybe something that's more biomarker-based as we think about moving toward pivotal development over time.

I will defer the question to you.

I would think the -- so event rate is a very positive sign in this trial, as you mentioned, Regulators have commented for pivotal trials and to request a co-primary endpoint of symptoms and an objective market that is either endoscopic possibility or radiology like the MRN geography. So what will be important with learning from the open-label extension with this low event rate is that low event rate is a clinically meaningful event for our patients, so that can be used, in fact, then to solidify the endpoints for a pivotal trial after the Phase IIb or even allow the Phase IIb to be the first pivotal trial on the registration process. Overall, biomarkers, if you refer to mucosal biomarkers or systemic biomarkers have not been sufficiently validated to count as surrogates for fibrostonosing disease. And so it will be a combination of symptoms endoscopy or imaging.

Great. Thank you for the question, Judah. So our next question comes from Anupam Rama at JPMorgan.

Yes, sorry about that. Congrats on the update. A question for the KOL, Dr. Ryder on the line. I know in your opening comments, you said this is a drug that should definitely be further developed. But I was wondering if you could expand on that with the emerging profile of tonosertib, how would you see a product like this fitting into your treatment paradigm? And how would you think about using it.

This is an excellent question. The -- in principle, and this is several steps ahead into the future. But in principle, if successful -- successfully developed and approved, this is a drug that could be anticipated to be given at diagnosis in combination with an anti-inflammatory drug to prevent stricter formation altogether. There would be an aspirational goal for several steps ahead. Regulators at this point in time required to start at patients with already established tissue damage and radiologically confirmed structuring disease to show efficacy. But ultimately, this drug will move if successfully approved. This drug will move earlier and earlier in the paradigm. And this could be either then going to a pre-strip state in patients that already have established Crohn's disease and then you prevent stricter formation in the short term, or then ultimately towards diagnosis, like I mentioned in the beginning. The second aspect that I found quite interesting that was from a biology perspective, a bit of a surprise. There were initial concerns that blocking TGF beta may be pro-inflammatory because it has immunoregulatory functions. But it seems the opposite seems to be the case based on the Part A of the study, the SCS CD inflammatory component, which is a surface area affected by inflammation, alter size, servers are affected by ulcers, also all trended towards improvement. And this opens the door to test ontonisartib also in the luminal Crohn's disease space because if it is anti-inflammatory and enter remodeling properties within the same drug could be very attractive. So in other words, I think the first steps have to be taken in established structures, but ultimately, the market for a drug that has these properties as we see them, if confirmed, the market will be wide open.

Thank you, Anupma for the question.

Did that answer your question?

Great. Our next question comes from Thomas Smith at Leerink.

Congrats on the data. For Dr. Reader, obviously, quite a remarkably low event rate in this OLE I'm wondering if you could elaborate a bit on how clinically meaningful the signal is to you? And maybe just expand a little bit on how you see these results and this event rate relative to some of the other contemporary publications, specifically the Vito and ustekinumab retrospective studies.

Yes. Thanks so much, Thomas. And I share with you that this was actually a very exciting finding in these patients. So the is this is not a direct comparison and it's an open label extension. So these are 2 limitations. I have to preface my answer with. Having said that, as I mentioned during the talk, I'm not aware of any data set showing this low event rate over this time period, patients with radiologically confirmed structuring disease. From a radiology perspective, these patients are all comparable. So the VERO study, the ustekinumab study and the standard of care outcomers study we ran in our consortium have all centrally read, confirmed constrict criteria, strictures on imaging. So this is very comparable, not just like centrally confirmed eligibility in Nova. The major drivers of event rates are the presence of symptoms, structure length, disease duration and others. And this is hard to match between these 2 cohorts because one is retrospective, one is prospective. But the delta between the historical cohorts being between 25% to 35% over 1 year and the 3% in Senova to me is quite remarkable. Compared with this is the low symptom burden at week 48 because going in, we didn't know what we would expect. These are patients that are imaging are obstructed. And at week 48, close to all of the patients are in clinical remission based on CDAI criteria. And even including obstructive symptoms that we elucidated through the SPO, the symptom burden is extremely low. And clinically, this is highly meaningful because these patients change their diet when they come in, they have abdominal pain after eating. And if you treat them in after 1 year, they're essentially completely asymptomatic. It's quite remarkable. But again, I want to also be cautious because open label extensions have a set of biopsies that are true for all open-label extensions not only for Nova but overall, the signs of this trial are very positive. So thank you so much for the question.

Super helpful. And if I could just sneak in a follow-up for the team. I know you mentioned now that we've established safety potentially looking at luminal Crohn's disease. Just wondering if you could elaborate a bit on the plans to advance a program in Lumina Crohn's and maybe Dr. Reader, if you could also opine on the potential role for ontonisertib in luminal disease.

Thank you for the follow-up question, Tom. We wouldn't have expected otherwise of course. As discussed, we remain very interested in exploring the potential of ontonisutib in luminal disease. We think that combining a direct antifibrotic mechanism of ontinitatib with an anti-inflammatory agent may really help address the therapeutic sealing that currently still exists in Lumino cranes. I think OLED was all about safety. Now that we have shown that we can dose chronically engross patients on top of standard of care. I think that's a major win. On top of -- on top of the safety profile, we also see a consistent picture where all parameters are trading in the right direction in the most difficult to treat tribologicapopulation. And of course, in essence, DeNova was already a combination study as well because we treat it on top of standard of care. I think for next step, it's too early to comment on exact time lines or design or combination in place, but we will surely keep you updated as our plans mature in the nearby future. Refer to Flow and Reader to discuss the potential positioning of antinitiative in the larger aluminum fields in the future.

I agree with what Tim was saying about the unmet need. So we are getting better and better with anti-inflammatory drugs, biologics and small molecules. And there's a huge pipeline in addition to what's already approved. But the all the drugs hit the ceiling and my prediction is even the combo players that are currently under investigation will hit a ceiling. And so the big unmet need is really an entire remodeling approach because multiple factors point towards tissue remodeling, being a predictor for negative response to biologics and small molecules. In other words, too much tissue damage gives you a poor response to anti-inflammatory. So you need to combine anti-inflammatories with the drug that addresses tissue damage. And that would be actually the first time this has been done with none and that would be a very reasonable combination partner for something like this. And then you may wonder, Thomas, about Crohn's disease versus ulcerative colitis. So Crohn's disease classically is considered the progressive disease with structures in small bowel structures, sometimes colonic structures. But really ulcerative colitis is emerging also as a progressive fibrotic disease, and we have done multiple studies confirming that there's significant amount of fibrosis also in UC. And so without wanting to expand the opportunities too much, but -- and Crohn's disease is probably a reasonable starting point. But in principle, remodeling drugs eventually will enter the space of ulcerative colitis as well, in my opinion, because the ceiling we observed in Crohn's, we also observed ulcerative colitis and remodeling maybe 1 reason why we can break the ceiling.

Great Yes, and thanks for the questions, Thomas. Our next question comes from Shannon Duffy at Piper Sandler. Shannon.

This is Shannon Duffy on for as Hemi from Piper Sandler. Congrats on this awesome data and particularly with the event rates being so low. Our question here is -- would you consider powering on that considering how low they are in the upcoming Phase IIb Nova era? And sort of how are you thinking about your ideal product profile from that result upcoming?

Thank you for the question, Shannon. I defer the question to Philippe, if still on...

Yes. So absolutely. Thanks so much for the question. I think indeed, the reduction in the event rate is very striking. I think it has the potential to become a stand-alone robust and pilfer registration. I think a reduction in these hard like outcomes will be seen favorably by regulators to support registration. This is the first observation in Cnova. It is still an over-label extension. We will certainly characterize the event rate very carefully with adjudication in the upcoming Phase IIb trial. And our basis, I think we'll make a decision whether this should be the primary efficacy end point for the Phase III program or whether we keep worthing perhaps on primary endpoint. I think this opens a new opportunity, which is very interesting and meaningful. So this will be really the objective for the Phase IIb to make a determination.

Great. Thanks for the question, Shannon. Our next question comes from Mani Soros at Cantor.

Congrats on the data really speaks for itself. Just a couple of quick ones. I guess, as it relates to, obviously, the event rate and the SPR, it seems like there's an opportunity here to kind of think a bit more critically about endpoint selection. I guess can you comment on your views in terms of the FDA on the U.S. side versus the EMA in Europe. How they're viewing and waiting things like APRO versus a more hard endpoint like an event-driven outcome? And then additionally to that, you mentioned that imaging, like MR might play a role as well. Obviously, there's a few measures there that you're showing some a bit more indicative of the signal than others. I guess would MRI be viable as something as a secondary where we'd be looking just at 1 component of the MRE measures?

Thank you so much for the question, Jan. I will defer the question to Philip.