Good morning, all. Good afternoon, and welcome to the Duvakitug Anti-TL1A phase II-B data presentation from ECCO. My name is Adam, and I'll be your operator today. If you'd like to ask a question during the Q&A portion of today's call, you may do so by pressing star followed by one on your telephone keypad. I will now hand the floor to Chris Stevo to begin. So Chris, please go ahead when you are ready.
Thank you very much, Adam. Good morning and good afternoon, everyone. Thank you for joining us to discuss these important data. We'll be making forward-looking statements in the course of this call. Any statements we make are only as of today, and we do not undertake any obligation to update these statements beyond this call. If you have questions about our forward-looking statements or risk factors, please see our SEC filings under Forms 10-K and 10-Q. And with that, I will turn it over to our host, Dr. Eric Hughes. Go ahead, Eric.
Thank you, Chris. And good morning, good afternoon, and good evening. And thank you all for taking the time to talk about this important program for Teva, our Duvakitug program. And if I can have the next slide. Before we get started, I know that Duvakitug is the star of the show today, but I did want to discuss what R&D is doing to support our pivot to growth strategy at Teva. We have really stepped up our innovative efforts at Teva, and I just want to briefly remind everyone that we have a number of programs in clinical development right now.
Our olanzapine LAI program in schizophrenia has now achieved its last- patient last visit and will be presenting that data in the second quarter of this year. Our DARI program in asthma is rapidly enrolling its phase III program now. Duvakitug will talk about today and ulcerative colitis and Crohn's disease, but [emrusolmin], anti-IL15, and anti-PD-1/ IL-2 are all in clinical-stage development at this point with multiple system atrophy, celiac disease, vitiligo, and our oncology program, so we're very excited about what we're doing.
B ut now I want to talk a little bit more about Duvakitug and the excitement around the TL1A mechanism at the ECCO Conference just last week. One of the important themes of the ECCO Conference was that we still have a long way to go with inflammatory bowel disease. There's over four million people with ulcerative colitis and Crohn's disease, and less than 50% of those patients achieve a clinical remission.
A nd I always like to point out that 75% of people with Crohn's disease and 20% of ulcerative colitis patients still require at least one surgery in their lifetime. So there is a long way to go to control this disease and bring relief to patients. Can I have the next slide? But why are we so excited about Duvakitug and this new mechanism of action by targeting TL1A? Well, TL1A is an amplification signal across multiple different inflammatory signals in the body. TL1A is secreted by a number of cells, immune cells, as well as mucosal cells.
And that cytokine, TL1A, then amplifies many different pathways in the immune system. It also might have a direct effect on fibroblastic cells as well. But why is this important? Well, these pathways have been implicated in a variety of different indications. Here we have a list that goes all the way from Crohn's disease all the way down to idiopathic pulmonary fibrosis. And there's many different things that we have the potential of exploring in the future.
It's important to note that many marketed products today only attack one of these pathways and can be indicated in a few of these indications. The potential of a molecule or a treatment that can treat across many different indications is very exciting for us in clinical development. Can I have the next slide? What differentiates Duvakitug in the way it was designed? When we developed our antibody here at Teva, we specifically targeted the interaction between TL1A and a DR3 receptor. This is the receptor responsible for the inflammatory signal.
We also proactively designed it so that it maintained the binding to the DcR3 receptor. This is a decoy receptor that the body uses to maintain a natural homeostasis during inflammatory responses. We strategized and selectively made the compound block DR3 while maintaining the DcR3 decoy pathway. Can I have the next slide? Now, I'll be passing this off soon to our guest speaker, but I just want to briefly remind everyone what the design of the phase II study for Duvakitug in ulcerative colitis and Crohn's disease was.
You could see that there were a total of approximately 240 patients enrolled. They were equally divided between ulcerative colitis and Crohn's disease. After a loading dose, they received either a high dose of Duvakitug, a low dose, or received placebo. The primary endpoint was at week 14. Those people who responded and then some of the placebo patients who got re-induced went on to a long-term extension trial. Just as a reminder, in ulcerative colitis, the primary endpoint was clinical remission by the Modified Mayo Score. For Crohn's disease, it was the endoscopic endpoint for the primary endpoint.
Can I have the next slide? Now, let me introduce my co-presenter today. We're very excited to have him with us. It's Professor Vipul Jairath. Professor Jairath is a gastroenterologist and a Professor of Medicine in the Schulich School of Medicine & Dentistry and holds the John and Susan Macdonald Endowed Chair in Inflammatory Bowel Disease Clinical Research at Western University in Canada. Professor Jairath leads the IBD Centre at University Hospital, London Health Sciences Centre, and is Director of the IBD Clinical Trials Unit, the Director of the IBD Fellowship Program, and is the Research Chair for the Department of Medicine at the Schulich School of Medicine & Dentistry. In addition, Professor Jairath is Coordinating Investigator for our Duvakitug IBD phase II clinical trial.
I will now hand it over to Professor Jairath to walk us through the data and to discuss his perspective on the data in both ulcerative colitis and Crohn's disease. I will then come back to summarize and open the call for questions and answers, and with that, over to you, Professor Jairath.
Great. Thank you very much, Eric, for the kind introduction and for everyone who's joined the call today. And these data that I'm presenting are fairly hot off the tail of just having presented these at ECCO two days ago. And obviously, there's been a lot of buzz around the results. So I'm going to start with ulcerative colitis first, and then I will move on to Crohn's disease. And I think, as Eric highlighted, I just want to say two other things that were very novel about this trial. One was the basket design, which allowed concomitant assessment of both ulcerative colitis and Crohn's disease within the same program. And that's really a first in our field, so it was very innovative, number one.
Just starting with the ulcerative colitis cohort, 133 subjects were randomized, 44 to the placebo group, 47 to the 450 mg group, and 46 to the 900 mg group. 89% of the placebo patients completed the trial. All patients in the low dose completed the trial, and all but one subject completed the high dose. There's a very high completion rate, 99% in the patients treated with Duvakitug. As expected in the placebo arm, it's typically AEs or lack of efficacy, so nothing unsurprising. There was just one AE that led to a discontinuation in the high dose. Very high completion rate, which, and this is what one wants to see when we're looking at drug versus placebo. Next slide. Here are the baseline characteristics of the patients coming into the trial.
I think on a very high level, I would say that these, despite there being 40-50 patients per group, these really reflect the typical moderate- to- severe population that you'd see in an inflammatory bowel disease trial today. So the mean age was around 40, a slight preponderance of male subjects. No surprise that most of the subjects were recruited in Eastern Europe, and I think that reflects most IBD programs today. And that's related to access of therapies for routine care. Disease duration about seven - eight years, typical for an IBD study. And I think it's clear that the patients had inflammation going into the trial. 56% had a Mayo Endoscopic Score of three, and that number is typically between 50%-60% in our program. So this gives a lot of internal validity around the patients going into the trial.
40% were on steroids, slightly lower proportion on placebo getting steroids, but these were just chance imbalances given the size of the trial, and then in terms of prior advanced therapies, 69% had not been exposed to prior therapies. 20% had been exposed to one advanced therapy, 4% to two, and then 7% to three or more. Next slide, so here are the primary endpoints of clinical remission at week 14. Again, this is the regulatory endpoint for ulcerative colitis. This was seen in 20% of patients exposed to placebo, 36% in the Duvakitug low dose giving a 16% delta over placebo, and in 48% of subjects on the high dose giving a 27% delta over placebo just for induction, so that's a large effect size at the end of induction for the high dose.
You do see a dose-response, what looks like a dose-response relationship by looking at this. The other novel aspect about this trial, from my perspective as an investigator, is A, the basket design, of course, but B, that there was a Bayesian analysis used here. The Bayesian analysis was based on a posterior probability that the response rate in any Duvakitug dose was more than 90%. And this was observed in 95% of patients on the low dose and 99% posterior probability in the high dose. These were both highly significant. And the corresponding odds ratios were 2.2. Using frequentist design was 2.2 for the low dose and 3.6 for the high dose versus placebo for the primary endpoint of remission. Next slide. We then stratified here the clinical remission rates by experience to advanced therapies and naive to advanced therapies.
And if you look at the middle bar chart here, experience, I think the key thing is that the placebo rate falls down to 7%, as expected in an experienced population. And the effect sizes are 22% over placebo for the low dose and 29% over placebo for the high dose. And as you move to the naive population, I think one of the key points is that we see similar levels of efficacy and delta versus placebo for the high dose. But of course, the placebo rate goes up. So the placebo rate is 28% in the naive population. With the absolute clinical remission rate 39% in the low dose and 53% for the high dose. So again, giving a 26% delta over placebo. Next slide. Across the secondary endpoints, again, we see higher absolute efficacy for the drug over placebo across all of these.
There are no p-values here, as this is not adjusted for multiplicity testing. Clinical response between 70%-80% for the active drug arm versus 50% for placebo, and for endoscopic improvement, which is an MES of zero or one, again, you see this dose-response relationship of 50% for the high dose over placebo, and then increasingly, we incorporate histology into clinical trial endpoints for ulcerative colitis, and if we look at the HEMI endpoint, histological endoscopic mucosal improvement, this is a Mayo Endoscopic Score of zero or one and a Geboes Score of less than 3.1, which is a histology scoring scale allowing just up to 5% of neutrophils in the lamina propria. Again, we see almost double the effect size in active drug arms versus placebo, so that's stringent endpoint. Next slide.
Really, just to say about the safety results, there were no dose-dependent effects and no trends were observed across safety categories. And all the AEs of special interest were non-serious and transient. These were typical things that will be expected along the course of an ulcerative colitis trial, so infections, a couple of hematological abnormalities, but really no major safety concerns seen. And there were importantly no clinically meaningful changes in laboratory parameters, vital signs, or EKGs seen. Next slide. Then this summarizes the most common AEs that were defined as seen in more than two participants in any treatment arm. These were upper respiratory tract infections, nasopharyngitis, vomiting, and anemia. These are typical things seen in IBD trials, and none of these AEs were serious, and they were all self-limiting. Next slide.
Just to summarize the ulcerative colitis section, Duvakitug induction demonstrated statistically significant clinical remission rates versus placebo with an effect size of up to 27% in patients with moderate- to- severely active ulcerative colitis. The additional secondary endpoints of clinical endoscopic endpoints supported the efficacy of Duvakitug in this population, and it was well tolerated with no emergent safety signals supporting the further development of this as a potential treatment option for patients with moderate- to- severely active ulcerative colitis. Next slide. Okay. From here, I'm going to move straight into Crohn's disease cohort. Just as a reminder, the structure of the trial, as Eric outlined at the start, was the same. This was a basket design allowing both populations to be assessed in the same protocol with a 14-week endpoint.
In this case, 138 subjects were randomized, 44 to placebo, 46 to the low dose, and 46 to the high dose. There was a high completion rate in the Duvakitug treated patients, 85% overall. 80% completed the trial in the placebo group. Again, typical reasons were withdrawal due to lack of efficacy, AEs, or clinical deviations. 80% also completed the trial in the 450 mg dose for similar reasons for dropout, and 93% completed the trial in the high dose. Next slide. Baseline characteristics of this population, again, as typically seen in a moderate-to-severe Crohn's disease population in a trial today. The mean age was 39, slight preponderance of male subjects. Most of the recruitment in this case happened in Eastern Europe, about 57%, but a quarter were actually also recruited in North America.
The disease duration was about 10 years, so this is a fairly refractory population. They were clearly inflamed. The SES-CD score endoscopic measurement of 12, a mean score, and the CDAI score above 300, and about a third of the subjects overall were taking steroids, slight imbalance between the groups, but I think that's by chance. Compared to the ulcerative colitis population, the Crohn's population was more refractory overall coming in, meant by 43% had not been exposed to advanced therapies, and 57% had been exposed to advanced therapies, 26% to one therapy, 16% to two, and 14% to three or more, and this was by design because no cap was put on the number of therapies patients could have failed coming into the trial. Next slide. Here are the primary endpoints.
The endoscopic response rate, which is a 50% reduction in placebo, was seen in 13% of subjects in placebo, 26% in the low dose giving a 13% delta, and 48% in the high dose giving a 35% delta over placebo. The analysis also was a Bayesian analysis. The trial was designed that the posterior probability of the response rate in any Duvakitug dose was greater than placebo was over 90%. The observed posterior probability for the low dose was 94%, and more than 99% for the high dose. These were highly statistically significant. The corresponding odds ratio by a frequentist design was 2.4 over placebo for endoscopic response to the low dose, and 6.1 for the high dose. Next slide. Similarly, these results were then stratified by patients who were bio-naive to therapy.
In the experienced group, as expected, you would see a very low placebo rate of just 4%, 7% delta for the low dose, but a 44% delta for the high dose, where endoscopic response was seen in 48% of subjects versus 4%. In the bio-naive patients, the absolute endoscopic response rate was almost identical to those in the experienced group, but the placebo rate was higher as expected, yielding 25% delta over placebo in the naive patients. Next slide. All of the secondary endpoints support what we saw in the primary endpoints. So we see a dose-response relationship for endoscopic remission, going from 17% and 26% versus 9% on placebo.
Then for all the clinical endpoints by clinical remission or response by the CDAI and clinical response by the PRO2, which is just abdominal pain and stool frequency, again, we see absolute higher rates in the drug-treated arm than placebo. For response, deltas of around 12% over placebo and for remission, 10%-15%. Next slide. Coming to the safety results, these were similar observations as we've seen in the ulcerative colitis population. Serious adverse events were seen in five subjects in placebo, six in the low dose, and one in the high dose. These were typically self-limiting infections such as COVID, herpes simplex infection, and bronchitis. There was one case of perirectal abscess in the placebo group. So these are typical and expected. There were no deaths.
And for AEs of specialist interest, again, similar to the SEs, four in the placebo, five in the Duvakitug, and three in low dose, and three in high dose. Again, there were no dose-dependent effects and trends observed. Most of the AEs of specialist interest were non-serious and transient. And there were no clinically meaningful changes in laboratory parameters, vital signs, or EKGs. Next slide. Again, looking at most common AEs occurring in more than two participants in any treatment arm, these were anemia, headache, and nasopharyngitis. So typical things that we've seen in IBD trials, and they were non-serious and self-limiting. Next slide. So in conclusion, Duvakitug induction demonstrated statistically significant and clinically impactful endoscopic response rates against placebo in moderate-to-severe active Crohn's disease. The additional clinical and endoscopic endpoints really supported what was observed for the primary endpoint.
The drug was well tolerated. There were no emergent safety signals. And I think importantly, these are the first placebo-controlled data for one antibody in patients with Crohn's disease. And they support the further development of Duvakitug as a potential treatment option in moderate-to-severely Crohn's disease. Okay. Next slide.
And I can take that from here, Dr. Jairath. Thank you for presenting it, and thank you for being one of our co-investigators in the study. And I just wanted to summarize by saying we believe Duvakitug has a potential best-in-class profile. We think of this by design because the basics of drug development, the fundamentals spoke to the results we saw. We designed an antibody that had high potency in vitro, high selectivity for the DR3 receptor, low anti-drug antibodies. We've noted a rapid and profound suppression of free TL1A.
As Professor Jairath mentioned, the safety profile and the tolerability has been very good to date. We're excited by these results, and we're working very hard to be starting our phase III program with our partner, Sanofi, in the second half of this year. With that, I just open the line up for questions and answers, and we can answer any questions you've got.
As a reminder, if you would like to ask a question on today's call, please press star followed by one on your telephone keypad now. Participants are asked to limit themselves to one question and one follow-up per person so we can get to all voices in good time. Our first question comes from Umer Raffat from Evercore ISI. Umer, your line is open. Please go ahead.
Hi guys. Thanks for taking my question. I have two here, if I may. First, for the doctor, thank you for the slides. Do you think this molecule is differentiated over the other TL1As? Second, do you think—second, and maybe this one is for Eric, actually—the rate of ADAs, could you remind us, Eric, where that may have tracked in this trial? And more importantly, what was the definition and the cutoff used for defining ADAs? Thank you very much.
So yeah, I can take the second first, Professor Jairath, if you don't mind. So we didn't have the data available at the presentation, but since then, we actually have seen ADA rates of about 3%-5%. So that's a very low rate at this point. In fact, we had seen below 10% in our first asthma study, but 3%-5% was very encouraging to see.
Umer, I don't have the exact cutoff for our assay, but we can definitely get that to you later on, but to your other question, Professor Jairath, maybe you can speak to your thoughts about the differentiation of Duvakitug compared to other compounds in development.
Yeah. No, thanks for the question. I mean, of course, there's no comparative data between the molecules, so anything here is hypothetical. That said, when the molecule was developed, and my understanding around this, it was specifically developed to preferentially block the interaction with DR3 receptor because this is an amplification signal, essentially. Upregulation TL1A is an amplifier. And the molecule was designed to preferentially inhibit the interaction with DR3 to dampen down about downstream signaling on a whole range of cells.
I mean, this interacts with many types of T regs and T cells, cytokines, and also fibroblasts, but also to try and maintain natural balance of homeostasis with a DcR receptor. So DcR receptors are there to try and maintain some natural homeostasis. So the molecule was actually designed with that. So in theory, this may be differentiating. I think, obviously, all of that will have to pan out in eventual phase III clinical data across the compounds.
The next question comes from Ash Verma from UBS. Ash, your line is open. Please go ahead.
Great. Yeah. Thanks for taking my question. I have two. So maybe one for Dr. Jairath. Broadly speaking, where do you think the TL1A class as a whole takes market share from existing therapies in IBD? And then second, on formulation, maybe Eric, if you can comment on this. So when you mentioned previously that the 450 mg and the 900 can get to a subcutaneous injector, how many milliliters are we talking about? And I believe your other competitors are maxing out at a dose of 500. So at this 900, are you still confident that you would be able to achieve that? Thanks.
Dr. Jairath, did you want to talk about the class in general and its potential use in the future?
Yeah. Thank you. I'll take. Thank you, Ash, for your question. I'll take the first question. So I mean, with the caveat that these are phase II data, and of course, we'd want to presUmerbly, if we see similar effect sizes in phase III, when you look at the—if I take ulcerative colitis first, when you look at the effect size of placebo of 27% for the high dose, I mean, in my mind, if you look at the comparative field, this is almost JAK-like efficacy, right? So I think if you look at the bar, what's the bar for ulcerative colitis? What's the highest efficacy rates that we see in the clinic today? In comparisons, it's really JAK inhibitors. And I think the same principle applies with Crohn's disease as well because seeing endoscopic response rates just after induction with effect sizes of 35% and even higher in bio-experienced, 44%.
Again, the thing that came to my mind when I saw these data is that this is JAK-like efficacy with potential safety advantages as well. I think that's the first thing, and the second thing to say is also that this trial involved sub-Q induction and sub-Q; it was all sub-Q therapy as well, which I think is also potentially differentiating, so when you look at both bio-naive and bio-experienced subjects, you get similar efficacy in ulcerative colitis across both, so in theory, it could be put anywhere in the treatment paradigm, and for Crohn's disease, even greater efficacy in the experienced population, but overall, as we say in this field, efficacy is king, right? Efficacy trumps everything else, so in my mind, again, I'm making indirect comparisons, but we do that all the time when we pick agents and where we position them. I think this looks as good as the best agents that we have today with potentially some safety advantages.
Professor Jairath, your comment on the subcutaneous was a perfect segue into the formulation question. And it's worth reminding everyone, Ash, that this whole program has been done with subcutaneous dosing. So our transition into phase III is like for like. From the very beginning, we've been doing that. So to your point, we're still doing the modeling and simulation. We're very excited to see the dose response in the study. That helps our model a lot to determine where the dose response hits a point of inflection. We have prepared already our prefilled syringes that are given subcutaneous for phase III, and that will be the syringe we use and our autoinjector.
To your question, though, the number of injections and how we give that, the schedule, is yet to be determined. We're working with Sanofi right now to design the phase III. And when we make the announcement, you'll be able to see how we're giving it in that program. Thank you for the question.
Thanks.
The next question comes from David Amsellem from Piper Sandler. David, your line is open. Please go ahead.
Thanks. So I just want to clarify on the phase III, and maybe it's too early for you to answer this, but are you going to be testing both doses in phase III or just the high dose? And then secondly, will the presentation be the prefilled syringe? Or just to clarify, will you have the autoinjector incorporated into the phase III? And then lastly, if I may sneak in one, you mentioned JAK-like efficacy.
I'm particularly interested in Crohn's, how you see Duvakitug being positioned versus RINVOQ, particularly given the safety tolerability baggage associated with RINVOQ. Ultimately, do you see the class being positioned ahead of the JAKs in Crohn's given the effect size? Thanks.
Professor Jairath, maybe I'll give you the JAK-like question first.
Yeah. Yeah. And just to comment on that, I mean, I think the first thing to say is that endoscopic, I think that having endoscopic response as a primary endpoint here was, in hindsight, a very good choice because it's the most objective outcome measure. And we know that endoscopic improvement, response, remission, however you define it, is associated with better outcomes for patients. And we see a large effect size here at 14- weeks. I think you're quite, and the analogy of JAK-like efficacy is my analogy, right?
This isn't something that I've heard colleagues on Teva line say, but it's my analogy when I look across all of the compounds. As a reminder, JAKs are in the U.S. our second-line therapy. They are positioned second-line. That's the label because they have a black box warning. I think it varies in different parts of the world, but certainly in the U.S., they are second-line agents because of some of the safety concerns. Now, if the phase III for TL1A produces, again, we need 52-week maintenance data and beyond, but if it produces the same safety that is seen in the phase II, then naturally, when you're seeing a patient and you've got two drugs with almost similar efficacy, but one has a better safety profile overall, it's obvious which one you're going to pick, the thing with the better safety profile.
Yep. Thank you. And the question regarding the phase III design and the prefilled syringe, so our final design is yet to be determined after we have to have our discussions with health authorities, and it has to be the result of our modeling and simulation. So whether we have one or two doses in the phase III has not been necessarily decided at this point, so I can't necessarily answer that question. Then that's up to the work we're doing with our partner, Sanofi. Your second question, we will be going into phase III with our prefilled syringe. So that's the syringe that goes in the autoinjector, which is developed in parallel. So we're intending to launch with an autoinjector at the end of the phase III program. Hopefully, that answers your questions.
Yep.
Thank you.
Helpful. Thanks.
The next question comes from Jason Gerberry from Bank of America. Jason, your line is open. Please go ahead.
Thank you. Thanks for my questions. So for me, for Dr. Jairath, I'm wondering, you talked a little bit about the comparisons on JAKs. One thing I've heard from some of your peers is, I guess, the value of TL1A having something like an ENTYVIO-like safety profile. And so I guess, based on what you've seen for TL1As collectively and what you understand about the mechanism, just kind of curious how you'd maybe compare the safety of Duvakitug or the TL1As to ENTYVIO from a potential safety and labeling perspective. And ultimately, ENTYVIO's commercial success was, I guess, underpinned by the VARSITY trial in doing head-to-head studies. So is that the cost of admission to getting a high level of usage, you think, in UC given the competitive intensity of the space? Thanks.
Yeah. Thank you. It's a great, great question, actually. Thank you for bringing that up. I mean, I think the first thing to say from safety, I think it's just way too early to make any comparative assumptions about how this will benchmark against other drugs. We've only seen phase II results. There's three phase III programs, potentially others coming. So I think time will tell us about safety signals. I think your point is exceptionally well made that I think for this whole field, it will be very important that TL1As do have a head-to-head trial built in somewhere. Whether sponsors choose to take that on in their pivotal phase III trial with an active comparator or whether a III-B head-to-head, I think it is essential that there is somewhere in the development phase a head-to-head both in UC and both in CD because I think your point is really well made.
Vedolizumab, really, in ulcerative colitis, it was a major turning point when VARSITY showed superiority to an anti-TNF. And I think if you see these kinds of data in phase III for TL1A, then there should be a high level of confidence to conduct head-to-head trials in both indications. And I think that would be really important for positioning. I suspect that these would be done as III-B-type studies like VARSITY.
Thank you.
As a reminder, that's star followed by one, to ask a question today. And the next question comes from Chris Schott from JP Morgan. Chris, your line is open. Please go ahead.
Great. Thanks so much. Just two questions for me. Maybe just first on the Crohn's side, I think you mentioned RINVOQ, but can you just talk a little bit about how you're seeing TL1A compared to IL-23s given those drugs emerging as kind of maybe more of a frontline standard of care? And then my second question was on biomarkers and how extensively you're going to look at those in phase III. Obviously, we see some great phase II overall data here, but were there any learnings from this study in terms of populations that could see even higher efficacy, or do you think that becomes less relevant just given the strength of the overall phase II program here? Thank you.
Professor Jairath, did you want to take the questions?
Yeah. I'll take the IL-23. There's a good question about IL-23 inhibition because I think if we looked at the treatment landscape in Crohn's disease over the last 10 years, it was clear that IL-12/23 inhibition has become certainly in North America and many parts of Europe first-line therapy. Now that we have three IL-23s almost, we've certainly got one IL-23 for Crohn's, and we'll have two more probably followed quite fairly soon. And a head-to-head in TNF failures demonstrating superiority of IL-23 over ustekinumab. I think your comment is right that IL-23 is starting to chip away at the ustekinumab first-line starts. I think that's probably correct. I think IL-12/23 still have an important role, particularly because it's curated subcutaneous dosing and there's flexibility in the dosing, which some of the IL-23s don't have.
And then I think you'll, and I think what we're learning as time goes on is, of course, we have some more safety data for IL-23 inhibition. We only have a couple of years of follow-up in IBD, but there is in other indications, and it's pointing towards a favorable safety class overall. So I think it would be important coming in in the TL1A landscape to really address that with comparative effectiveness studies because to my point around JAKs, JAKs are positioned second-line in the U.S., whereas IL-23 inhibitors are not. And I think it would be important to address some form of comparison to IL-23 inhibition if TL1A is going to take first-line position. The second thing to add, though, is that some of the science that underpinned TL1A development was around potential antifibrotic actions as well.
Those need very specific studies to address that, but I think it's one of the potential advantages over other classes as well. Again, the clinical studies will need to be done to show that.
And I can answer a little bit of it. I can start off with a biomarker question if you like, Professor Jairath, and I'd like to get your opinion on it, but with biomarkers, we're looking at all the normal players: genetic readouts, proteomic readouts, biopsy readouts, serum readouts. In my experience, I think that discovering a baseline biomarker for prediction of response requires a lot of data, especially in disease areas like this, so we're collecting that. We're hopefully to, well, identify something. We do something that's a little bit unique compared to other programs is that we look at free TL1A as well.
Whether that pans out or not, we'll have to get more data. But for right now, given the data we've seen in both treatment-experienced and naive patients, we're approaching this as an all-comer program, but we'll certainly be looking at more data in larger patient populations as we move forward to hopefully identify a predictive biomarker or even one that's on treatment response. But I know that's a perennial question at the meetings, Professor Jairath. What are your thoughts about biomarkers?
Yeah. No, thank you. I mean, look, I think the Holy Grail would be that we develop a companion biomarker for any of our drugs. We were 25 years into advanced therapy starting with anti-TNF, and to date, we don't have one. And so I think if it was easy, it would have been developed, and we're really left with clinical parameters.
I think whether other TL1A inhibitors, the companion biomarkers, pan out, it's really important that we have to see this within the phase III programs, number one. I think the second thing is that if there is a clear companion biomarker, how would clinicians actually use that? Would it be that you only use the drug if you're biomarker positive? And then there's lots of things that influence that. How prevalent is the biomarker in the background population, and what is the true delta that you get? I mean, if you're only getting 5% delta with a biomarker, you probably wouldn't really care much. But if you've got 15% or 20%, or maybe even 10% at least, it may be that we only use the drug if you're biomarker positive and not biomarker negative. So I'm not clear how it would pan out.
We'd have to have a really significant effect size with a companion biomarker, and Crohn's disease, particularly, that's really challenging because it's not one condition. Ileal disease behaves differently to colonic disease, to ileocolonic disease, and perianal disease, and EIM, so I think part of the challenge is that IBD is a multisystem disease with, particularly in Crohn's disease, differential behavior according to where the disease presents and when it presents as well.
Thank you.
The next question is from Balaji Prasad from Barclays. Balaji, your line is open. Please go ahead.
Good morning. This is Michelle for Balaji. Thanks for taking our questions, so first of all, with the JAK-like efficacy profile, especially in the treatment experienced group, have you considered maximizing the induction phase opportunity in the drug development process as in the induction phase, the efficacy is more important versus dosing interval?
Also just a quick follow-up on the remission phase data. Wondering when should we expect 52-week clinical data readouts? Thanks.
Professor Jairath, did you want to answer that question about what would you prefer, better efficacy or better schedule, two or four weeks, or a more intensive induction? What are your thoughts about that?
Well, yeah. I mean, it's an interesting question. I mean, I think if we look back over drug development in our field for the last 25 years, we've always had this theory that we have either IV drugs or IV induction followed by sub-Q. All separately here. And the notion being that you've got high inflammatory state and you get this antigen sink, and you need to give an IV dosing to get really 100% bioavailability to really kickstart and mop up all that inflammation and get sub-Q dosing.
I think this program, albeit at the phase it has, and other parallel programs ongoing in the IL-23 space, which is sub-Q induction, totally challenge that concept, right? It shows that you can give sub-Q induction, and you're getting very favorable efficacy rates with sub-Q induction. So in the end, I don't think I guess the question for the phase III is again, and I'm not privy to that information, is what's the dose selection going through in? And there'll be lots of modeling from here, from the data seen here. And I think it's getting the dose right in the induction phase and trying to get the total area under the curve of drug exposure during that time.
But you're absolutely right that we probably believe that if you get really good efficacy induction, that will probably carry out into the maintenance period, particularly with half-life of drug and carryover effects. And I think you said it before that efficacy is king. So that would be definitely where we want to design the program around it. Yeah.
And the second part of the question was, I believe, about when we'll be having some data on our long-term follow-up. I believe it was. And the study finished its primary endpoint in the December timeframe or November-December timeframe, and it's a 44-week follow-up study. So we're anticipating the last patient, last visit sometime in December of this year. So shortly thereafter, we'll be presenting that data. Thank you for the question.
At this time, there are no further questions. So I'll hand the call back to Dr. Eric Hughes for closing comments.
Let me start off by saying first, thank you to Professor Jairath for being in the conversation today, and thank you for being one of our presenting authors of the program here just last week in Berlin at the ECCO conference. I thought it was very exciting to see the data presented and to see it in the context of all the other things going on at the meeting. Thank you for everyone for taking the time today. We're excited to be working with our partner, Sanofi, to get our phase III program going. At the end of the day, we hope to have a program and a compound that can help relieve people of their ulcerative colitis and Crohn's disease in the future. Very exciting, and thank you all again for calling in.
This concludes today's call. Thank you very much for your attendance. You may now disconnect your lines.