The Society for Investigative Dermatology meeting, where Corvus and its collaborators have two papers, two posters, and the pleasure of having two of our speakers, two of our presenters speak here today with you. This is a very exciting time for Corvus. I think you'll see both from some of my introductory remarks and from the speakers that we have here today, that Corvus really does have a very special compound that's going to have applications in many, many areas of medicine. Let me start with our forward-looking statements and introduce the today's speakers in addition to myself. I'm very happy to have Dr. Albert Chiou here. He's a Clinical Professor of Dermatology and the Director of Clinical Research in the Department of Dermatology at Stanford University Medical Center.
Along with Albert, Dr. Kavita Sarin. Kavita is a professor of dermatology and an expert in precision medicine and genetics, also in the Department of Dermatology and also in the Cancer Institute at Stanford. I picked these two speakers for a reason. Yes, they're very smart. Yes, they're very photogenic. More importantly, they complement each other. That is clinical research together with the science and elucidation of mechanisms, which is going to hold for us the promise of new applications and better ways to use our drugs and understand them better. These two speakers really complement each other and really add to the scientific prowess of Corvus. They make us smarter, and they set new standards, higher standards for us every day. Let me start with the agenda for today.
I will make some introductory remarks. Then we'll have Dr. Albert Chiou talk about the treatment landscape for atopic dermatitis, as well as review the clinical data from our phase I trial. Interestingly, we heard this morning from Kavita Sarin on the biomarkers, that was probably would be better to have the clinical first, but the schedule of the meeting, you know, we can't control. Dr. Sarin went first, but she gave a brilliant talk and is gonna go through that again for us. After Dr. Chiou, Dr. Sarin will go through the immunologic and biomarker data. I use the word immunologic deliberately. It's more than a biomarker. It's fundamental biology. We have learned new things about this disease and about the immune system.
I'm gonna follow Dr. Sarin's talk with some key takeaways if I'm able to summarize their beautiful work, as well as talk about our pipeline. I hope we have time for a Q&A, both from the people in the room and those in the back. You guys can move up here. We have more seats up in the front. We'll have Q&A from people in the room here as well as on the webcast. I know we have a very large audience on the webcast. With that, just some details on the papers that we're talking about. On the left, Dr. Sarin's talk was this morning and really beautiful talk. I hope that you can look at her slides and go through it.
She is gonna cover most of that today. There's a poster session this afternoon with her data, and she'll be there and able to answer questions in more details if you have any. On Saturday morning, Dr. Xu is going to deliver his paper on the phase I clinical results. I think that's gonna be a very important paper. The poster on that paper will be tomorrow afternoon as well. A lot of details that they're not able to cover in the 10-minute talk. Okay, let me start with sort of get everyone grounded. soquelitinib is a first-in-class drug. Why is it a first in class? Other people have talked about ITK, a target, and I'll get into that more in a moment.
Really, nobody was able to make a drug that just hits ITK, and that's because it's hard to do. ITK has several closely related enzymes called the Tec family kinases. Some of those just have one or two amino acid differences in their structure in their ATP binding site. I'll tell you in a bit why we were absolutely fastidious about the specificity. We have a novel mechanism of action. First in class drug with we believe now broad opportunities because it can control so many important functions in the key immune cell called the T cell. The mechanism of action is dependent on a high degree of selectivity for ITK, and this enables it to block many different pathways.
Also to reprogram T cells so that you can have a lasting effect beyond the drug, kind of like when you vaccinate somebody. They're vaccinated, the drug is gone, you're immune for a while. This is sort of the same thing. The immune system has memory. It's programmable. Thank God for that, because otherwise we'd have to take medicine every day. Oral administration, we're studying this drug mainly BID dosing. We believe eventually it's a QD administration. It's now in a phase III trial in a very bad disease called peripheral T-cell lymphoma. It's a registration randomized trial in peripheral T-cell lymphoma. We're now enrolling our phase II trial, randomized double blind study, phase II in atopic dermatitis, similar to the patients that you're gonna hear about in a few minutes from Dr. Chiou.
We plan to start studies in other diseases, hidradenitis suppurativa later this year, and asthma. That's just the beginning because we think that this really is a pipeline in a product, and I know that's a cliché, but this really could be that. I had the privilege of working on an antibody called Rituxan. That was a pipeline, a product in a pipeline too. Of course, it could do all different kinds of lymphomas. You could treat various autoimmune diseases. I look at this in a similar way. The opportunity is vast. Pulmonology, gastroenterology, dermatology, oncology, rheumatology, just to name a few. Strong IP. We have issued patents, composition of matter patents. It's issued in all the major territories. You can look up the patents.
Those protect us in those territories through to 2042. We have a bunch of patent applications covering things like methods of use, monitoring TH2, TH1, Tregs, et cetera, all kinds of other permutations of that, working their way through the U.S. PTO. Management team. We've done this before. My colleagues and I have done this before. It's called Rituxan. It's called ibrutinib, and a couple of others, BRAF inhibitors. We know how to take drugs or biologics that have big opportunities and get it done, and we're all driven by science, medicine, good clinical research, and development. That's what we pride ourself on. Okay, now let's talk a little bit about the mechanism, because I think we can make some really important points here. ITK stands for Interleukin-2-inducible T-cell kinase.
It's been around a long time, as I mentioned, and it's known to be crucial in many T-cell functions. T-cell receptor signaling, T-cell differentiation, apoptosis. Many, many T-cell migration. It's important in many, many areas. We know that it's fundamental in the differentiation of a naive CD4 cell into what are known as TH17 cells, TH2 cells, and TH1 cells. Those are the three main types of helper T cells. The TH1 cell, that's important cell. Fights cancer, fights infection. TH2 cell, important in protecting also against certain infections and tissue homeostasis, regeneration. Same thing for TH17. TH17 and TH2 cells are the cells we're gonna focus a lot on today because they're involved, they're heavily involved in inflammatory diseases.
It was shown by Pam Schwartzberg and Leslie Berg 25, 30 years ago that if you knock out ITK gene in a mouse, just ITK, what happens, as shown on the right here, is that you can't make TH17, you can't make TH2, because they're dependent on ITK. Consequently, you can't make those cytokines. What are those cytokines? IL-4, 5, 9, 13, 31, GM-CSF, TNF-α. When you think neutrophils in some of these diseases coming from there, GM-CSF. Interestingly, when those workers made that knockout mouse, they still were able to produce TH1. Why was that? Well, the TH1 cell has a redundant enzyme known as RLK. Sometimes in the old literature it's TXK. You may see that terminology sometimes. Okay, the genetic studies showed that if you knock out ITK, you skew to TH1, you lose TH2, TH17.
Interestingly, I know there's a lot of companies out there who are saying, "I got ITK inhibitor too." Most of them hit RLK. The genetic studies show if you hit RLK and ITK together, you get T-cell dysfunction. You're severely immunocompromised. Of course, we don't wanna do that in autoimmunity. What we did at Corvus is say, "We wanna do this." Our strategy, the inventive step, the aha moment. The aha moment. Every great company has a aha moment. Was, "Hey, we gotta make it specific for ITK and not for RLK." We weren't really that smart, even though we were saying aha, we're not that smart. We just went to the library and read a lot. That's helpful.
The important thing to tell you about Interleukin-2-inducible T-cell kinase is that it's not all over the body. It's just in T cells and NK cells and ILC2s. We don't have time to talk about ILC2s today, but they're really important in immunology and in autoimmune diseases, asthma, atopic dermatitis, other diseases. The specificity of the drug for a target that is only in T cells and NK cells. That's really very important. When we hear about mechanism, you're gonna hear a lot of stuff about mechanism from Dr. Chiou and Dr. Sarin, remember, it's limited to those tissues, to T cells, and T cells can orchestrate all these different kinds of immune effects. I told you memory was part of the immune system. There's a second important component, diversity.
It can do a lot of things. One day you're getting a virus, the next day you're getting a bacteria, the next day you're getting a fungus. You don't know what's I mean, we're getting assaulted every minute. Trust me on that. The strategy, make an ITK specific drug, and we were able to do that, okay? We've published that. All right? We have an oral ITK specific drug. It is a covalent drug, by the way. That's one of the ways we confer specificity. I wouldn't go into the details of that, but this morning there was a question about covalency. Well, yes, it's covalent, but the protein turns over in 12 hours. The drug is out of your body very quickly. The half-life of this drug in the body is in the plasma rather, is 2-3 hours. Okay?
There's no lasting effect of the drug once you stop it. Pretty much gone. In a mouse where we can give radio-labeled compound, we know 99.99% is gone in 24 hours. This is the mechanism of action. If we can make a drug that can block ITK and spare RLK, we may inhibit TH2 and TH17 and spare TH1. That's a good thing. Okay. Now, each of these cells has characteristic transcription factors, so we can elucidate them, we can measure them. We can look at them in the body and the blood and so forth. GATA3, ROR gamma t, TBET. You'll hear about another one pretty soon called FOXP3. In fact, you're going to hear about it right now. The story got much stronger in the last few years.
Now there is no question, no question whatsoever, there was just another paper last week that came out from a group in New York, that TH17 and Tregs are suppressor T cells. They're the brakes on the immune response. Anytime you react to microbe or whatever, you make an inflammatory response, something's gotta shut it down when the microbe goes away. Those are the Tregs, among other things. ITK turns out to control the differentiation of TH17 and Tregs. When you block ITK, and this was done by Avery August using our drug, it was also done by him genetically, you stop TH17 and you skew towards the Treg. There's no question about that anymore. We've seen that in every experiment we do in the lab.
5 or 6 different labs have shown that, and we now see it in our patients in atopic dermatitis. Oops. Okay, where does this leave us? Well, we have a drug, very specific, for a target that's only in your T cells, which is not all over the place. It's very restricted. Yet we have the ability to block various cytokines, the TH2 cytokines, 4, 5, 13, et cetera. TH17 cytokines, like IL-17 and 21 and GM-CSF and others. We can increase Tregs. I'm not gonna go into the ILC2 story here, but that's an emerging very important part of the story. Now comparing that to some of the approved agents, I mean, which you already know, those are stoichiometric. If I give an anti-IL-13, I'll block IL-13 for sure. I won't block the other things.
I'm not really changing the function of the immune system, I'm blocking a ligand. JAK inhibitors, of course, they can modify T cell responses. Many of these targets of the current drugs suffer from the fact that many, many tissues express the target, notably the hematopoietic system and the immune system. If we look at some of the stats or some of these other receptors or proteins, signaling proteins, they're not just in T cells. They're in T cells, B cells, myeloid cells, erythroid cells, et cetera, et cetera, et cetera. I can't name them all. I don't remember them all. They're throughout the system. That gets a little scary if you wanna treat people for long term, if you wanted to do that with agents that are perturbing fundamental processes in the body.
Okay, that's the foundation here. The foundation for taking soquelitinib into the clinic in immune diseases. We were already in the clinic in T-cell lymphoma. The reason why T-cell lymphoma is attractive is because those are TH2 cells, they frequently involve the skin, and they're really going crazy. They have no respect for the patient. They grow and grow and grow. We think we can inhibit them in a large number of patients, and that's a phase III trial that's going on now. Along the way, as we began to put pieces of the puzzle together, as we started to do more experiments in the lab and preclinical models in animals and so forth, we began to realize that, "Hey, autoimmunity and inflammatory diseases would be great." That led us to atopic dermatitis.
TH2 disease involves the skin, many of the same cytokines involved, and you can see the disease very easily. Plus, I was friendly with Albert Chiou and Anita. No, not really. I am friendly with them, but that wasn't the reason. Anyway, so with that, with that, it is my great pleasure now to turn the podium over to Dr. Albert Chiou. I think you're gonna find his talk extremely exciting.
Just a quick mic check. Is this coming through? Great. My pleasure to speak here, and I actually really love this format because I get a little more time than at the actual symposium talk to double-click on the details here. Like Richard mentioned, my name's Albert Chiou. I'm a medical dermatologist over at Stanford. I serve as our department's director for clinical research, and I've been involved in clinical trials for atopic dermatitis, including some of the early dupilumab trials, the IL-13 inhibitors, a number of the JAK inhibitor trials, and then now soquelitinib.
I also take care of a large number of patients with moderate to severe atopic dermatitis who are on systemics, including a busy practice where we see a lot of the folks referred in from the community who have failed first and second-line therapies. Maybe I'll just start first with a reflection. You know, atopic dermatitis is not, it's not a lethal disease, but it's a highly morbid disease. It is really tough on our patients. This is a combination of factors. One is that, especially in our adult patients with moderate to severe disease, for most of them, this is going to be a chronic lifelong issue. They deal with very unpredictable flares, and that in itself is very, very hard on people psychologically.
You just have this daily bother from itch and frequent complications like skin infections. It really hits a lot of aspects of patients' quality of life, their health. What's really interesting about this patient population is there's a lot of varied patient preference on what is the ideal treatment for them. Even my most severe patients, what I find is that we're oftentimes balancing these discussions of efficacy, but also what each individual is willing to accept in terms of side effects. There's also a lot of variation in what they'd accept in terms of treatment duration and what happens if they miss a dose or come off the treatment. With this context, love to talk through the therapeutic landscape right now of at least our approved therapies that we're using right now in the clinic.
First and foremost, we have to acknowledge dupilumab, you know, our first real targeted treatment, and that and our IL-13s now the mainstay first line for atopic dermatitis, and that's primarily because of the excellent safety profile. They don't have broad immunosuppressive effects. In this disease, safety is paramount. One thing we have to keep in mind, I'm an adult dermatologist, and I know a lot of our need is in adults, but a lot of this disease burden is in children, where safety is even a higher bar. That being said, with these biologics, we know the targeted monoclonal antibodies, there can be variable response.
Remember in the, depending on which of the dupilumab trials you take a look at, about 30%-60% of patients don't hit EASI 75, which is a high threshold of clearance of the skin. Patients have to be comfortable self-injecting themselves with subcutaneous medications, and that just adds to patient hesitancy, requires a lot of hand-holding from our staff. Finally, they do have side effects. If you look at dupilumab, the IL-13 inhibitors in particular, conjunctivitis, injection site reactions, these are all things that come up when you talk to patients about this. For the patients who want an oral medication or essentially are reaching for a little bit more efficacy, the JAK inhibitors have become really helpful tools in our toolkit. That being said, we have to acknowledge their limitations.
They have a really hefty black box warning that infections, blood clots, death. You can imagine, this really adds to the hesitancy that patients have about starting them. They require regular blood monitoring, which again, just another barrier to patients willing to start this. I do think that with all this here, there is a tremendous need for additional treatments for atopic dermatitis, especially those that can address some of these aspects of the disease I just mentioned. First and foremost, we have to acknowledge that there are a lot of patients who don't respond to any of these first or second-line therapies or have some side effect or contraindication to them.
We always need something with a novel mechanism of action that can capture some of these patients and rescue them. That's just very, very clinically important. You can take this a step further. Let's say that imagine that you're a fly on the wall for one of these conversations with these patients where they're first indicating their interest in moving beyond topical therapies, trying to get into a systemic therapy.
I think the most frequent refrains you'll hear are something along the lines of, "Hey, is there a safe pill that I can try for a while?" Very rational questions like, "If I start this medicine, am I stuck on this for the rest of my life?" "What happens when I stop it, when I decide that I don't wanna take it anymore?" We're in this current landscape, having a lot of these nuanced conversations about trade-offs. We are talking about potential side effects, blood monitoring, if you're talking about the JAK inhibitors.
If you're being really honest, you have to say, "Gosh, you know, we have great data that if you stop this medicine, you have an 80% chance of flaring and needing some sort of rescue medicine, potentially within weeks." That's where we're at. If we take a step back, we are in a far better place now for atopic dermatitis than when I first started, when we're just using conventional immunosuppression. That being said, I think our patients are asking us to do better, and that's why I think it's so important that we have clinical trials like this and development of treatments like soquelitinib that can offer more to this really large and important patient population.
With that, I'll jump into the study design and clinical data that we're presenting here at the SID. Here's the study design. This is a randomized, placebo-controlled, blinded, dose exploration study looking at soquelitinib for moderate to severe atopic dermatitis. You can see here that we have 72 participants and kind of the standard entry criteria for moderate to severe atopic dermatitis that is focused on adults here. Patients who are required to have failed a prior topical or systemic therapy, and that will come into play later when we talk about the prior systemic exposures. For the first 2 cohorts 1 and 2, patients were evaluated for soquelitinib at the same total daily dose, but either at split or once-daily dosing.
Cohorts 4 essentially doubled that dose to evaluate them at the highest tested dose in this trial. Cohorts 1 through 3 were randomized 12 patients to active treatment and 4 patients to control, and they were treated with just 4 weeks of active treatment. Cohort 4 here, I'll kind of point out, is an interesting one. There are a total of 24 patients in this cohort. They were randomized 1-to-1 active and placebo, these patients were actually evaluated for 8 weeks of total duration of treatment, so giving us a peek at what happens with an extended course of treatment. Here are our patient characteristics here at baseline.
You'll see here, these are cohorts 1 and 2, cohort 3, a pooled cohort 1 to 3, then the cohort 4, which again, those are the patients that received 8 weeks of total treatment, so twice as long as the other 3 cohorts. Kind of if you just look closely at the actively treated patients versus the placebo-treated patients, you'll see they're actually well-balanced between them in terms of baseline demographics, baseline EASI scores, and proportion of prior systemic therapy exposure. One of the things we did observe is that as we got into cohorts 3 and 4, the baseline EASI severity actually crept up, and we think that's basically due to the nature of the recruiting sites that activated by that point in the trial.
I think one interesting point about this trial population is a fairly high proportion of patients who are exposed to systemic therapy, so more than a third, which is not the case in many of these atopic dermatitis trials. Most of those prior exposures were dupilimab, but the representation of other AD systemic therapies. Let's jump into the efficacy results. This is seen here for cohorts 1 through 3. Recall these are the patients treated for four weeks of total dosing. We'll take a look here for cohorts 1 through 2, looking at EASI 75 and IGA 0/1. These are really important endpoints. They traditionally have been co-primary endpoints for pivotal trials for atopic dermatitis.
We can see, for the lowest-tested total daily dose, cohorts 1 and 2, we're actually starting to see patients hit these responder thresholds at just four weeks. If you take a look at cohort 3, these are the patients who received double the total daily dose compared to cohort, 1 and 2. You'll see an even more impressive EASI-75 and IGA 0/1 responder rate there, particularly if you look at EASI-75. Notably, for these patients, none of the placebos were able to hit any of these responder thresholds.
If you take a look at EASI 50, EASI 90, and the mean percentage reduction EASI, you'll see very similar directional results, with improving scores for cohort 3 at the highest dose, especially when you compare to placebo. Here's a plot of the mean percentage reduction in EASI for cohorts 1 through 3. What you'll see here on the vertical axis is the actual change in EASI % from baseline, then horizontal axis is time, of course. Then I'll just point you towards that middle white period. This is the actual 4 weeks of active treatment that these cohorts 1 through 3 patients received. All the way on the right in the gray here is a 30-day follow-up period off any active treatment.
They're followed up 30 days after the last dose to see how their skin and safety is doing. In orange here is the placebo group. This is a pooled placebo group from cohorts 1 through 3, and you'll see them in the top curve there. In blue and red here are cohorts 1 and 2. Again, these are the patients that got treated with the same total daily dose. You can see that their curves overlap almost perfectly, and they do start to separate from placebo. You can start to see that occurring at day 15, and that becomes very apparent on day 28. Here's the really interesting part about this trial. At the follow-up, you actually see maintenance of that clinical response.
I was involved in the other trials for JAK inhibitors and other therapies. This is something that you don't often see in atopic dermatitis, where the disease frequently comes back after treatment. In cohort 3 here in the green, what you can start to see is a dose response. These are the patients treated with double the total daily dose. You have a earlier and deeper response. You can see it as early as day 8, statistically significant, day 28, and again, that maintenance of response here. Would love to double click on that part of it because as a clinician, that's what really popped out to me with those data. First of all, the efficacy, of course, the rapid deep response, but also this durability.
What's interesting in this slide is that this is a real focus on cohort three, and these patients, unique to this cohort, were followed up to 90 days after the last dose. What we can see in this cohort, you have that early and deep response, but then you actually have durable maintenance of that improvement all the way to the last date of follow-up. We actually don't see deterioration even through the last follow-up visit. We don't know how long this persists because we've ended it, and it's continuing. I don't wanna steal Dr. Sarin's thunder 'cause she's gonna help us look into the biomarker and potential mechanistic explanations for this durability.
I will just point out too, if you really look at this cohort 3 population, you'll actually see that they have increased T regulatory cells in the blood, and that's especially apparent when you compare them to placebo in the lower dose treated patients. If you recall from the mechanism, we know that ITK's activity shifting us from TH17 inflammation over to those T regulatory cells. That could provide a potential mechanism for why we see this clinical durability. This is just a reminder of what happens in real life when you treat patients with other medications with this rebound or worsening of the skin disease. These are three of our approved therapies and just an investigational product. The JAK inhibitor is kind of a classic example, highly efficacious.
In the clinical trials and just clinical experience, you can see once you stop the medication, that skin improvement starts to deteriorate pretty rapidly, oftentimes within 2 to 4 weeks. Just anecdotally, my patients tell me that they miss a dose, they'll feel that itch starting to come on even before the signs start to change on their skin. Even with Dupilumab, which is a biologic, we know from the SOLO continuation studies and just from clinical experience, this is where day zero is actually when they completed their 16 weeks of Dupilumab, and they were randomized to other doses of Dupilumab or essentially stopping it by being switched to placebo.
You can see that deterioration in the skin control at that point as well, seeing hints of that as early as 4 weeks, but definitely by 8 weeks. This is just 1 more example of another investigational product, the STAT6 inhibitor. What you can see there is that, at the end of treatment, you can start to see some of that clinical deterioration as well. Now, let's take a look at cohort 4. I actually really love this slide because this gives us a sneak peek at what happens if you try to extend the duration of therapy. Cohort 4, unique in this study. These are the patients that got 8 weeks of active treatment. Again, the 1-to-1 randomization, active to placebo.
Here we see the highest degree of EASI 75 and IGA 0 and 1 response. At this 8-week treatment duration, we are seeing some patients in placebo hitting EASI 75, very, very low compared to the actively treated patients. We see directional results in the same manner, EASI 50, EASI 90, a mean reduction in EASI. Just really pointing out 75% of these patients are hitting EASI 75, which is, as a clinician, something you're really excited about. At this treatment duration as well, we're starting to see the placebo patients flare as defined by requiring rescue medications. We had a couple patients that flared here and none on the soquelitinib treated.
Just plotting out here the response curves, and what you can see here in orange is the placebo group. What we see is this continuing to deepen response curve for the cohort 4. Again, highest treated dose, also the longest period of treatment, and then that clinical durability seen again at the end of that treatment period. I will point out that that slope does not start to plateau. At 2 months of treatment, we do not see a plateau in the improvement of the EASI scores there. This slide I think is very illustrative if you're just trying to take a look at all the different cohorts and kinda their EASI-75 and IGA 0/1 response.
On the left here, we're taking a look at cohorts, 1 through 3, again, treated for 4 weeks. In the solid bars here, we can see the EASI 75 responder rate. In the striped bars, we can see the IGA 0 or 1 responder rate. You can see this pooled cohort 1 to 3. At the end of just 4 weeks of treatment, we are seeing EASI 75 and IGA 0 and 1 response. Interestingly, that is maintained day 30, day 60, and day 90. Again, we are not just cherry-picking the responders here. This is the total population and maintenance over that timeframe. Cohort 4, what you're seeing here is again, longer duration of treatment.
You have a superior EASI-75 and IGA 0/1, and then maintained at the 30 days of follow-up. We then asked the question, what happens to the folks who've had prior systemic therapy exposure? Again, a kind of a marker for more severe disease or tougher phenotypes. This pools all 4 cohorts together, so you can see the placebo group versus the soquelitinib-treated groups, and you see separation of the curves in terms of mean % reduction in EASI. Over here on the right panel, you can see the patients with prior systemic exposure. Even that placebo group is only the placebo-assigned patients who had prior systemics and actively treated patients with prior systemic exposure.
You can see it continues to have that separation of the curve, suggesting good activity within these patients with prior exposure. This is the one I love as a clinician. This is the folks who knock on my door. These are the patients with prior systemic failures. Taking a look again at the patients with the highest total daily doses, they were able to identify 6 patients with prior systemic failure. All of these patients have failed dupilumab, many other additional agents, including some with a couple failed agents. What they were able to see is 3 of those 4 patients actually improved on soquelitinib, 2 markedly so. Both patients who were assigned to placebo ended up flaring, again requiring rescue medications.
I think from a clinical perspective, this really gives us a lot of excitement about the potential activity of soquelitinib in patients with prior treatment failures. Just turning over to a summary of our safety here. This is taking a look at cohorts 1 through 3, again, 4 weeks of active treatment, and then cohort 4, which is 8 weeks of active treatment. What we can see is that the frequency of adverse events is well-balanced between active and placebo-treated patients. Actually, in the folks with the longest exposure, placebo ended up with more adverse events. There were no severe or serious adverse events. No patients discontinued due to AEs. Here's the granular safety table, and again, taking a look at cohorts 1 through 3, and then cohort 4, the longest exposure.
Kind of, the big takeaway here, again, a mix between placebo and actively treated patients, again, pretty well spread across. Most notably, there was no hematologic or laboratory abnormalities, and there was no infectious signal in the safety data. Some patients treated with soquelitinib reported a headache. Apparently that all occurred at a single site, and most of them were transient, lasting less than a day, so hard to read into that. Overall takeaway, a really clean safety profile, especially from our interests with relation to infections and lab abnormalities. In conclusion, we present our phase I clinical data about soquelitinib.
We're really excited about this ability to target TH2, TH17 inflammation, and also potentially start to shift into these Tregs for atopic dermatitis. So far we see a clean safety profile, no infection signal, no lab abnormalities. Again, we can attribute that to the tissue selectivity of this medication. We saw a early and deep response with a relatively short dosing period of just 48 weeks. Again, this is a phase I trial. Again, that speaks to the broad targeting of TH2. We also see durable treatment effects with patients with prior systemic exposure, including prior systemic failures. Finally, just, I think we'll tee up my colleague Dr. Sarin here. We're really excited about this mechanism.
We think that this might actually provide promise for other conditions with autoimmune inflammatory disease, especially with this potential mechanism of rebalancing immunity. Thanks so much.
Thanks, Richard. Given the time, I think we'll hold questions until the end. It's now my great pleasure to introduce Dr. Sarin. Before I do, I always like to say that, you know I have something else to add. Before I do, I always say it starts with the patient. What do we observe in the patient? We observe clearing of skin lesions. We observe safety. We observe a durable effect. Then we go into the laboratory and we say, "Okay, well, how do we explain this?" One of the things I think you're gonna learn from Dr. Sarin is the translation here is absolutely beautiful, and portends for, I think I believe, success, not only in atopic dermatitis, but many other diseases as well. I'm really looking forward to you, your talks, Kavita.
I also understand that following Albert is a difficult task.
Thank you very much. Thank you, Richard. Thank you, Albert. That was a great talk, really excited about the clinical efficacy. I get to present the really fun stuff, which is what is happening underneath the skin that explains this clinical response. It gives me great pleasure to present the immunologic data from soquelitinib for atopic dermatitis. Richard did a such a beautiful job going over the mechanism, I do wanna just highlight it one more time so that this is the basis of all of the studies that we'll be presenting so that everyone is on the same page. As Richard mentioned, ITK is a T-cell signaling kinase that's primarily expressed in T-cells, NK cells, and ILC2 cells. ITK plays a critical role in mediating TCR differentiation and TCR signaling.
What's really important to understand is that ITK is not equally required across T-cell programs. Genetic studies have shown that loss of ITK preferentially suppresses TH2 and TH17 responses, but spares T-immunoprotective TH1 responses, and that is due to compensation from a related kinase called RLK. The second important thing to know is that ITK plays a critical role in immune switching between TH17 and T regulatory cells. Loss of ITK has been shown to shift cells away from TH17 programs into Tregs. As Richard mentioned, that is the beautiful design of soquelitinib, which was designed to suppress selectively ITK but spare RLK, thereby suppressing TH2 and TH17 immunity, but sparing TH1 so that we retain protection against cancer and other infections. This biology is central to atopic dermatitis, which is primarily driven by type 2 inflammation.
As Albert mentioned in his beautiful introduction to the landscape of therapies, many of the therapies that are currently very effective for atopic dermatitis suppress these TH2 cytokines in this pathway, IL-4, IL-13, and so on. They are effective, but they're not necessarily durable as Dr. Chiou mentioned. ITK inhibition is happening just upstream at the T-cell programming to shift away from TH2 and TH17 programs, and so really can lead to more of an immune reprogramming or a shift to suppress these downstream cytokines. Dr. Chiou also did a great job going over this. I'm gonna be extremely brief and summarize the whole trial in 1 single slide. This was, you know, a phase I placebo-controlled study and patients were enrolled in 4 cohorts.
In the first cohort, patients were treated for a total of 4 weeks at increasing doses of soquelitinib. In the fourth cohort, patients were treated for a total of 8 weeks at high-dose soquelitinib, 200 milligrams twice a day. Now, for this t-talk, I wanna draw your attention to 2 things. The first is that it was placebo-controlled, but the second is that every cohort had 30-90 days of follow-up off of treatment, which allows us to look at the durability of response. I'm also gonna summarize all of the work that Albert just presented into a single slide, which really highlights 2 things, the clinical efficacy, which is significant improvement in EASI scores in 4-8 weeks of treatment and the second thing, which is the durability.
If you look, both 30 to 90 days off of treatment, none of the patients had a recurrence of their atopic dermatitis, no one had a rebound, and no one required any rescue medications. This is why it's so interesting to peek underneath the skin and see what is happening immunologically. From an immunologic standpoint, we investigated the effects of ITK inhibition on Th1, Th2, Th17, and Tregs. The assays were looking at serum cytokines, blood flow cytometry, and PBMC single-cell RNA sequencing. This is the first finding. Soquelitinib reduces Th2 biology. On the bottom left is PBMC's data showing a dose-dependent reduction in proliferating Th2 cells. The Th2 cells are down. On the right, we see a significant reduction in Th2-related cytokines, IL-4, IL-5, and IL-13.
We also see a reduction in TARC, a TH2 chemokine, which is directly associated with the activity of atopic dermatitis. I wanna call your attention to the gray shaded area here to highlight a very interesting finding, which is that even 30 days after treatment, so during the drug-free period, the cytokines continue to decrease. The second interesting finding is that soquelitinib led to an increase in persistent Tregs. On the top here, you can see that soquelitinib led to an increase in Tregs marked by CD4 positivity, CD25 high, and FOXP3 as compared to placebo in the high-dose groups, the 200 milligram twice a day as well as the cohort 4. Here's what's really interesting. Those Tregs continue to persist after the 30-day drug-free period. This may actually explain the durability of response that's seen clinically.
When we look more closely at the TH17 Treg axis, we see the following. Soquelitinib increased BATF2, which is a transcription factor that's involved in promoting T cell stability and Treg stability and longevity in the high-dose group. On the bottom left here, you can see increased BATF2 expression in the high-dose group treated with soquelitinib as compared to placebo. Conversely, treatment with soquelitinib led to a decrease in ROR gamma T, a master transcription factor for TH17 cells. This suggests that soquelitinib may be playing a direct role in regulating that TH17 Treg axis. What is one potential mechanism behind this? Well, one is that ITK has been shown to sequester BATF2 in the cytosol through downstream phosphorylation.
An inhibition of ITK by soquelitinib may release BATF2, so it can translocate into the nucleus and induce transcription of genes such as FOXP3, promoting Treg longevity. The third finding, which is relatively unexpected, was that soquelitinib led to inhibition of the JAK-STAT pathway. On the top, we observed that SOCS3 expression increased in circulating T cells, including TH2, TH1, and Tc17 cells. On the bottom right, we observed that JAK1 signaling was suppressed, along with STAT6. This is important because, as Albert mentioned, the JAK-STAT pathway is central to atopic dermatitis, and STAT6 is central to IL-4 and IL-13 signaling. This was somewhat unexpected because ITK is not known to play a direct role in the JAK-STAT pathway. We believe this may be happening through sort of the T cell immune reprogramming from T away from TH2 and TH17 programs.
This is also important because that suggests that maybe this JAK-STAT inhibition may be more selective in the T cell programs. In conclusion, soquelitinib is an oral selective covalent inhibitor of ITK that spares the related kinase, and it appears to be rebalancing Th2 and Th17 responses, suppressing Th2 and actually shifting Th17 responses towards a Treg program, with persistent Tregs even after the drug is discontinued. It also appears to inhibit the JAK-STAT pathway in the T cells. Together, this may explain the durable remission that's seen clinically as well as its favorable safety profile. More broadly, this really highlights a new paradigm for treating inflammatory conditions. Target upstream at the T cell differentiation node, shift away from the inflammatory T cell programs while preserving the immunoprotective T cell programs, reprogram immunity and the potential for durable control.
With that, I'd like to turn it back to Richard.
As I told you, seldom in my experience in medicine do you see such a consistent translation where all the things just sort of line up with the proposed mechanism of action, and more importantly, the clinical findings. That's really beautiful. I have the task, and I do wanna leave time for questions. Why are we excited about soquelitinib? It's very simple. We may be modifying the underlying biology of the disease, okay? We're not just blocking a cytokine or blocking a receptor. We're changing the disease. We're disease modifying. That is a big, big statement, and if confirmed in other trials and other diseases, really does change the paradigm, as Dr. Sarin's last slide mentioned. It's even better than that because do you realize that those Tregs are antigen specific?
Okay, they're not just suppressive. A Treg has a T cell receptor and is only suppressing a particular antigen response. Did you realize that the TH2 cells that were decreased were, as she said very cleverly, proliferating TH2? We can figure that out with our science. It's not just blocking every TH2 in your body, it's the proliferating ones. Those are presumably the ones that are associated with the ongoing inflammatory reaction, okay. The precision, and she's an expert in precision medicine, is really amazing. We may be modifying the underlying biology, and that represents a new way to think about therapeutics, treatments, monitoring, et cetera. Is it worth it? You bet it is because I don't know of any patient who wants to take a drug forever. Every drug has side effects.
Every drug has chronic implications that may take years to figure out. Most people wanna take a drug for a while and go off of it, hopefully never come back. If it does come back, do it again. My own personal experience as a physician at Stanford treating patients with Rituxan was patients got 4 weeks of Rituxan, then it went to 8 weeks. Then 70%, 80% didn't need it again for 30 months. When they came back, guess what? They wanted it again, and they wanted it again after that. I had patients in my clinic who I gave Rituxan to 10 times, because it worked, it was well-tolerated, and it gave them a good remission. They didn't have to take pills and come in and do all kinds of stuff. They had a simple infusion, they were done.
New paradigm, we're modifying the disease. I don't need to go through the details here. You've already heard blocks Th2, Th17 rebalances Tregs. I do wanna emphasize that those Tregs are not just suppressive, they're antigen-specific suppression. That's why it was the Nobel Prize last year in medicine. Not for me, unfortunately, but for the people who discovered it. The profile for us now that's emerging, I want you to think about this, is a shorter treatment period. 28 days gave you a durable response. I mean, maybe a longer duration would give you even more durable response. That's a question that will need to be answered. Remissions are durable. We see activity of people resistant to treatments, not just had other treatments, but failed a dupilumab and a JAK inhibitor in 1, in 1 case, a cytotoxic.
We may be in an era where maybe we don't need to treat you for a year, and unfortunately, you stop your drug in a year, and 2 weeks later the disease is back. Okay. If you look at all those studies that Albert alluded to, the rebound occurs in 4 weeks or less. That's why we didn't have to follow patients for more than that. Really wasn't worth it. We weren't seeing any rebound. Every other agent, the rebound occurs within 2 weeks. Finally, just again to remind you, we are enrolling a phase II randomized double blind trial in atopic dermatitis. Really quickly on that trial, I've shown this before, 12 weeks of therapy, moderate to severe AD, very similar to the patients that we just described to you.
4 arms, placebo, 200 mg QD, 200 mg BID, 400 mg QD. We are looking at QD dosing and, of course, a placebo. They're equally balanced. It's completely randomized. It's a global study. The primary endpoints will be the typical what's your EASI score at 12 weeks and then, of course, the other secondary endpoints. This study's now ongoing. We expect to have data from this study around 3rd quarter of 2027. We have a very important collaboration with a company called Angel Pharmaceuticals. I'm pleased to announce that Dr. Charles Lee from Angel, he's the president of Angel, he's my boss, is here with us today. Charles and I and the team at Corvus and the team at Angel were very closely coordinating research and development. Angel has the rights to soquelitinib in China.
We have the rights in the rest of the world. This is the study Angel is doing. It's pretty similar to what we've been doing. 12 weeks of therapy. Moderate to severe AD. There are two cohorts. It is placebo controlled. We think placebos are important in this disease, even for the laboratory and measurements. Basically 100 milligrams BID, 200 milligrams once a day, placebo. We can look at the data then they go into the next cohort, 200 BID, 400 once a day placebo. We will have data from the first cohort, Charles tells me, or I guess he's gonna be in trouble, by the end of the year. The Angel team is doing a spectacular job. Again, we work very closely with them.
We have conference calls every week, going over patient selection and information and so forth. Once that's completed, the study automatically rolls over to phase II, 60-90 patients, treated, again, with a placebo, treated on one or two of the doses that are studied. So again, sort of to summarize, we think our results show that soquelitinib could become, I say leading oral, I mean leading therapy. Take out It is oral, but I think or a leading therapy period, for atopic dermatitis and possibly other diseases. We have positive clinical results. We have shown safety. We see deep responses, including in patients who are refractory to other therapies. That is very challenging patients.
We see durability consistently. Now, is that gonna are we gonna see 100% durability forever? Probably not. I'm sure that there's gonna be patients who fail at some point in the future, but we haven't seen it yet. We have, I think, identified immunologic parameters that support the mechanism of action that are gonna teach us more, that are already informing our second- and third-generation compounds. Okay, this is an iterative process. Take the patient, go back in the lab, make better stuff. I think there is a possibility of coming up with biomarkers that maybe will predict who does well, who has the more durable responses. Maybe it's a Treg, maybe it's a cytokine from the Treg, or something like that.
There's a lot of work to do, but we have something very special, and we're all over it. Finally, I use this bull's-eye slide to remind myself, I look at this every night, that it's the target. It's all about picking the good target. A target that has applications to a disease that's relevant and hopefully more than one disease. We've been able to make a very specific drug, the aha moment, the inventive step. Go for specificity over potency. We used to argue, "Hey, this one's more potent." I would say, "Yeah, but it hits RLK." No, I don't care about the potency as much. I like that, but I want the selectivity. I want both to get that. As you can see here, phase III in lymphoma.
Interim data from the lymphoma study later this year. I forgot to mention Angel data. Maybe I did mention late this year. We're really looking forward to the Angel data in their phase II later this year. Angel's also gonna be starting an asthma study, and I know they're preparing to file an IND on that as we are. I think you can see the rest of the opportunities here. ALPS, I didn't have time to talk about that. We are planning to present, hopefully present some of that data at the ASH meeting in December. That's a very interesting disease. Very rare disease, but very interesting. Again, teaching us a lot. Autoimmune lymphoproliferative syndrome. Bad disease. Finally our, you know, upcoming milestones. Phase II HS study, asthma by end of year.
Angel data, late 2026. ALPS data, ASH, phase III interim data later this year in lymphoma. Those are the near-term milestones for Corvus. With that, let's open it up. Maybe Dr. Sarin and Dr. Chu can come to the front, and we'll answer questions. I think we'll take the questions from people in the room. We can also open it up to the, to the webcast. Any questions for any of us? Mostly ask Albert and Kavita because they're smarter. Greg.
Yeah, oh, sorry. Hey, it's Graig Suvannavejh from Mizuho. Thanks for the presentation. Thanks, doctors.
I think investors who look at this data see it as early. It's promising, but it's early. We've got other programs that are out there as well. There were some references to JAK inhibitors and STAT6 and perhaps some other mechanisms of action. As maybe for Dr. Chiou, as you are involved in many clinical trials right now, as you see the ITK inhibition mechanism of action relative to the other mechanisms of action, is there any other aspect of what you're seeing with soquelitinib that beyond maybe the prevention of rebound or having long durative efficacy, at least at this stage, is there anything else that you would point to that helps to differentiate this versus some of the others where investors seem to be paying attention to equally, if not, if not more, so?
Thanks for the great question. Honestly, I was holding kind of bated breath for the safety data to come through. I think, just like I started with, I think safety is paramount in this disease. I think a lot about these pediatric patients that will eventually need something. On that particular point, it's great that we have dupilumab, which is a great treatment, but it's an injectable, which for kids is a big deal. A safe oral medication, I think just that alone, is something right there. I think the efficacy data, yes, really early. Just so promising, right. Especially looking at that 2-month, those seeing the 75%, patients hitting EASI-75.
I mean, you can put that up against most of, you know, these really promising investigational agents that are coming through right now. I think in terms of oral medication where you have just checking that safety box, at least from what we know, and again, really hoping that holds up in later phase trials, with that really promise of the efficacy, that's fantastic. Honestly, durability, so fascinating. That was icing on the cake, right? To come in after that. You know, I was just talking to someone earlier, if you kind of look at that cohort 4, 2 months of treatment and then maybe 30, sorry, 90 days of durability. I apologize, that's cohort 3. That's like about 6 months, right?
You can imagine, even if that's the worst case and it just, that durability plummets at the end of that, like 2 courses a year and that sort of response for AD, boy, that's a great conversation to have with a patient.
Thank you. Next question.
Hi, Tony Oro. First of all, I think the durability issue is, getting back to the last question, nobody wants to take this medicine continuously. Having the durability is the thing that really distinguishes this. It's amazing. I noticed that you that the highest dose also was the only dose that had blood levels of Tregs. It seemed like the more you go out, the longer the durability. What are your plans for, I mean, is it possible then to take it 2 months for 1 year? What do you think about that? I mean, that cause that is a game changer.
Thank you. First of all, we should not let that person in the room. He's a professional. Can I take that? Tony, Dr. Oro, you know, this is the data we have now. One month gives us Tregs that persist at this dose. Two months gives us Tregs that persist. I think a real question now is, does longer treatment give you even greater durability? Maybe you don't even need to give it for 28 days. In animal models, you don't need to give it that long, and you may induce this. That's another thing to think about. Can we even go shorter and generate the Tregs? We don't really know the answer to that.
In animal models where we can be a little more, you know, we can do more biopsies and look around, there's no question, you see Tregs infiltrate lesions, skin lesions very quickly. Same thing in asthma models. You know, that's new biology, and I think there's gonna be a lot of clinical questions. I think from a clinical development standpoint, not to worry. I think the clinical paradigm for approval would be 4, 8, or 12 weeks of therapy, placebo controlled. What's your EASI score? Now, if you wanna claim I can retreat somebody a second and third time, I think you are gonna have to go in the clinic and, and prove that. That's been done before, you know, with dupilumab and so forth, continuation studies.
Yeah, but the question was, why is this different from anything else? It's, I mean, that's the answer, is that it's the durability, non-injectable durability is a game changer.
Yeah. Thank you for that comment.
That's all right.
Any other questions? Zach?
Yeah. We have a couple from the webcast here.
Okay, great.
I'll start with one from Paul Choi from Goldman Sachs. For the doctors, what sort of duration or study size is needed to establish the benefit risk profile as safe?
anyone?
Yeah. It's a great question. I think one of the things that maybe we'll have to talk about is the duration of the clinical trial, right? This phase I. For a lot of the patients, only 30 days of follow-up after that dosing period. I think what we're seeing is that there is a pharmacodynamic effect that's persisting with that durability, which is a great finding this trial. I think we do have to follow these patients out many months. I'm starting to think about the other trials that have been run for, say, the biologic trials or others to just get a sense of that safety over that full exposure period of months after the last dose.
Which is a great opportunity as well to further evaluate that durability aspect of the medication as well. I know that, as we've been talking about the next phase trials, a lot of that is powered around kind of efficacy endpoints as well. I think maybe, if you wanna touch upon some of those considerations. At least what I'm thinking about is this drug is really interesting even after you stop the last dose, and that, having some of that safety follow-up for, you know, throw out a number, you know, 6 months afterwards, et cetera, just really understand what's going on there. Again, we haven't seen the end of the durability yet, at least from these initial phase trials.
I don't, maybe if Paul has a follow-up question on that. I wasn't sure whether he was asking about the safety in the off-treatment period or the on-treatment period. I mean, both are important, but I forgot to mention that in the follow-up period, the study is still blinded. The patient and doctor still don't know what they're getting during the follow-up. That's important point. One other point, as long as we're talking about placebos and controls, is as you can see from Dr. Chiou's safety slides, there's really no side effects that are, you know, that are worrisome to the patient. The placebo and the treatment were identical, basically. This is an oral medication.
When we say the trial is blinded, it really is blinded. Just think about if you were taking a drug that had injection site pain, and let's say it was 60 or 70% of patients. Well, that's not really a blinded trial, because, you know, the patient knows that they're getting the drug. And I see this, to me, this disconnect when in some of these trials where, you know, you got 20% of people getting conjunctivitis, you've got 60% injection site abnormalities, and they occur every time. How do you blind that? Well, the answer is it's not really blinded. Now, I'm not criticizing it. It's the best you can do. I mean, I think those studies are doing the very best they can do. It really does raise the question.
When we say blinded, I can tell you, 'cause I've swallowed some of those pills, they're not different. Okay? I don't wanna do it for a year, but it's, they're not different. It's impossible to know what you're getting. It really is blinded. Anyway, any other questions from the-
Yeah. We can move on to another one from Leiv Lea from Cantor. This is a 3-part, bear with me.
Uh-oh.
Immune markers, cytokines were lowered in the drug-free stage. What would be the explanation for that? Do you see that reduction from the placebo arm? Can you discuss what you saw in placebo arm in terms of rebound and biomarker changes? Last, how does the biomarker data read through to other potential indications for soquelitinib, the asthma trial, HS, et cetera? Can we expect to see similar durability effects?
Okay. I hope I can remember the 3 questions. The first question is the reason the cytokines are still falling in the drug-free period is because there's Tregs around and the immune response is still being, you know, inhibited. That's our explanation for why they continue down. You'll notice they bounce around a lot, cytokines. Measuring cytokines in these patients is very difficult because the timing is difficult. I mean, you know, every patient's a little different. You don't know when the optimum changes are occurring. Some of these cytokines are very short-lived. Like, I think IL-4 has a plasma half-life of 4 hours, so you can easily miss these things. We are noticing interesting things like IL-5 drops early, IL-4 later. What is the explanation for that? We're not sure.
Different subsets, as Kavita mentioned, different subsets of cells being affected differently. The answer to the question number 1, the cytokines continue to drop because of the ongoing T reg induced immune regulation. The 2nd question on placebos. Placebo cytokines jump all over the place, really don't give you any constant stuff. They could be down, they can be up, they can be down, they can be up. I didn't show that really for the sake of simplicity. You certainly don't get a consistent thing in a drug-free period. There's no question about that. The rebound question on placebo. If you remember those slides that Albert showed, placebos don't rebound.
I always get asked that question, "How come placebos don't rebound?" Well, because they don't respond that well. Remember, we had 0% EASI 75s, and they didn't get any drugs, so how, you know, in cohorts 1 and 2. If you don't have much of a response, it's hard to rebound. They're not getting treated with anything. Whatever the mechanism of rebound is in a JAK inhibitor or a DUBi or a STAT6 inhibitor, whatever that mechanism is, I wish I knew what the mechanism is, but I don't think anybody knows. It's really striking how quickly it occurs. I mean, within 2 weeks if you look at those curves.
Anyway, the question of do placebos rebound is sort of not really addressable 'cause they don't rebound. There's nothing to rebound to. I think the other question was.
The read-through for other indications.
We think the read-through is good because. That's why we're doing an asthma study, which again is thought to be TH2 driven and, you know, all the cytokines and things that we're thinking of are important in asthma. We are gonna do something a little different in asthma, and that is, given our mechanism of action, we do not need to restrict it to eosinophilic asthma. Let me say that again. That's double the population roughly. Because half the patients don't have eosinophilia. Most asthma studies require an eosinophil count of 300 or sometimes 150. That is eosinophilic or allergic asthma. We're gonna open that up wider.
And so I think the read-through is, You know, all I can say is that we've now looked at many different animal models, inflammatory bowel disease, asthma, psoriasis, atopic dermatitis, graft versus host disease, systemic sclerosis. I may be forgetting a few. We see consistent efficacy, robust effects in all of those diseases.
Okay. Next one from Etzer Darout from Barclays. Have you also looked at the placebo group EASI scores in cohorts 1 to 3 out to day 118? Also, do you have 90-day off treatment for cohort 4?
Let me take the last one. We don't have 90-day treatment for cohort 4 because we recognized that we didn't really need to do it. First of all, you gotta realize to do this requires an amendment to your protocol, IRBs, and you also have to pay for this. We were comfortable enough with what we saw with the Treg data from cohort 3 and from cohort 4 to say, "Okay, let's take our resources and double down on this in the phase II trial," which we're doing and where we will have 90-day follow-up. Okay. Placebos, placebos flare.
If you follow them in these I don't think we went over the flares, but I don't think we've ever seen a flare in a treated patient, but we do see it in the placebos. If placebos bounce around, as you know. Also remember another thing about our trial. Somebody else, I think, Greg, you asked this question. I would argue that the patient population we have is sicker than most of your AD studies. Why do I say that? First of all, 35% are prior therapy. Eight patients had failed, I mean, or refractory to prior therapies. Nobody takes those. Nobody takes those patients.
When you talk about a third of the patients and half of those are refractory in a study with only, you know, 50 subjects, that's a pretty big hit, potentially. Yeah, I mean, you know, we don't have 1,000 patients, and you need to do that at some point. We have a very robust clinical experiment where we took patients who were pretty sick, and we saw efficacy. You know, that's what motivates us to go on. I think that the data we've shown in a sicker patient population is as good as any data, any product under development I've seen. Even some of the ones approved, albeit they have, you know, hundreds or thousands of patients.
That's why we're excited about this. That's what we're doing.
Okay. Next question from Sean Lee from H.C. Wainwright. Seeing the inhibition effect on JAK-STAT pathway, would that potentially lead to safety issues long term? Does it matter to tease out the treatment effect from the Treg effect, or does it not matter?
I'm glad that he asked that question 'cause I forgot to mention that remember, it's not like we're blocking JAK-STAT in every hematopoietic cell. It's only in the cells that have ITK and probably only in those activated T cells. It's very restricted. Again, the fact that we're seeing changes in the JAK-STAT pathway, it's not because our drug is interacting with ITK. Let's make sure people understand that. Our drug does not bind any JAK. JAK 1, 2, 3. No. This is an indirect effect, and it's due to the fact that, and it's very clear when we in the patients that we treat with soquelitinib. SOCS3 stands for suppressor of cytokine signaling 3. It is 1 of the brakes. Remember, the immune system has gas pedal and a brake.
SOCS3, when you're trying to shut down an immune response, inhibits the JAK-STAT signaling because you're trying to cool things down. We're seeing patients' inflammation go away. We're blocking T-cell signaling upstream. Naturally, SOCS3 goes up. SOCS3 is going to block those pathways. That's almost a secondary effect. I don't think it's a primary effect. Again, it's nice to see this biology happen, right? It's nice to see that you're having this multitude of effects in conjunction with clinical responses and durability and all that other stuff. Just to be clear, we're not a JAK inhibitor. Some guys out there saying, "Oh, we're a JAK inhibitor." No, we're not a JAK inhibitor. We don't bind JAK. No binding to JAK. We affect SOCS3. SOCS3 will dampen JAK, some of the JAK-STAT signal.
Okay, that's occurring in only the cells that have the ITK target. That's not happening in your myeloid cell or your macrophage or any other cell. Okay? That's very important. It's very interesting to see that you really are shutting down this inflammatory response. You got Tregs. Well, first of all, what do you think Tregs are doing? They're trying to shut down the immune response. Wouldn't it be crazy if the immune system makes Tregs and turns on JAK-STAT signaling? You wouldn't, when you drive your car, step on the brake and step on the gas at the same time. Well, maybe you would, Jimmy, but you wouldn't do that. The immune system is dampening the response, Tregs and reducing JAK-STAT signaling.
That's an indirect effect, but very interesting because yet it's another clue to the fact that we have some very interesting biology going on. Unprecedented. Nobody's seen stuff like this before. Okay? Any other questions?
We'll do one more, and then I think we need to wrap up. Jeff Jones from Oppenheimer. Can you speak to what magnitude of change is typically considered clinically significant in regards to TH2 populations?
TH2. Oh, TH2 in general.
Well.
I mean.
That's a tough one. I believe that Jeff is asking the relationship between the degree of TH2 reduction and clinical response. We just don't have enough data to make those kinds of correlations at this point. That may be actually something, you know, to look at. Listen, we're working really hard looking at all of this, serum cytokine relationships to response, Treg in relation to response, all of those things. It's tough. You know, you're gonna need many more patients to make those kinds of correlations. What I said, this is human biology. I mean, it's highly variable. I mean, you know, as you can see, these patients are, some are young, some are old, you know, all different prior therapies, et cetera.
That's a great question, Jeff Jones, I don't think we have enough data yet to come to that. Should you get that, should you come up with the TH2 level that predicts response or duration of response, I would file a patent on that in about 10 milliseconds. Any other questions? Anyway, first of all, I wanna thank Albert Chiou and Dr. Sarin on really wonderful presentations. I mean, that was really exciting. I'm so inspired now, I don't know what to do with myself. I wanna thank the people in the audience here for attending. I wanna thank everyone on the webcast. I think that we have some really exciting data that we presented this morning, and Albert Chiou's presentation on Saturday, poster tomorrow. Kavita Sarin's poster also this afternoon.
Again, you have a chance to come by and hassle her even more. We look forward to seeing you at these posters, but I wanna thank everyone, and we're eager to report on our future progress. Thank you.