Hello. After you. Good afternoon, everyone. My name is Richard Miller, and I'm the CEO of Corvus Pharmaceuticals. Welcome to you all. I'm delighted to be able to give you an update on Corvus Pharmaceuticals. In particular, I'm going to be covering some data that was presented at the Society for Investigative Dermatology meeting a couple of weeks ago. I also want to go through, very carefully, our plans for going forward, and I want to leave enough time for questions. I also want to thank the Jefferies folks for inviting us to the healthcare conference. Let's get going. I know it's late in the afternoon, and I'll try to be as exciting as I can. First of all, soquelitinib is a first-in-class immune modulator which we believe has broad opportunities in immune diseases. Why are we so excited about this molecule?
It has a novel mechanism of action. It's highly selective for ITK, and that turns out to be a crucial inventive step. It blocks multiple cytokines and, we think very convincingly now, rebalances or resets the immune response. It's an oral drug in a market that's dominated by injectables. The clinical stage of soquelitinib is it's now enrolling patients in a phase II randomized, blinded, placebo-controlled trial in atopic dermatitis. It's also enrolling a phase III registration trial in peripheral T-cell lymphoma, which we'll talk about more later. This really is a pipeline and a product. I was one of the developers of rituximab, which of course became useful in many diseases in different areas, and I really believe that soquelitinib has the potential to be used across many areas of medicine. Dermatology, oncology, rheumatology, pulmonary medicine, et cetera. We invented this molecule, Corvus did.
Intellectual property is very strong for this molecule. Composition of matter patents have issued in the major territories, with pharma extensions go into the early 2040s, and there are many different patent applications underway covering methods of use, monitoring, and many other aspects. The management team at Corvus has a lot of experience developing innovative products, breakthrough products, big markets, and that's what we plan to do with soquelitinib. Let me start with the mechanism of action. The target is the key. The target here is ITK. ITK stands for interleukin-2-inducible T-cell kinase. First point to make about this target is it has limited tissue distribution. It's only expressed in T cells and NK cells, and another rare cell called an ILC2, innate lymphoid cell. Okay. The drug, soquelitinib, is very specific for ITK.
When you have a very limited tissue distribution and a very specific drug, that predicts or anticipates safety, because the possibility of off-target side effects or reactions is more limited. Specificity and selectivity is a key. That's what you strive for when you try to discover a drug. Okay. The mechanism of soquelitinib and ITK's function in the immune system is now very well defined. It is a very complex mechanism, but the components of it have been very well described over the past 25 years. As shown on the slide here, ITK is involved in the differentiation of normal helper T cells into what are known as Th1, Th2, and Th17. You've probably heard about some of these cells and a lot of these diseases, atopic dermatitis, asthma, psoriasis, et cetera.
The Th2 and Th17 cell produce a lot of important cytokines that are involved in many immune diseases: IL-4, IL-13, IL-5, IL-17, and several others. The Th17 cell produces IL-17, important in diseases like psoriasis, hidradenitis suppurativa, and other diseases as well. On the right side of this slide is what happens when you knock out or you block ITK. This was first discovered 20 years ago by genetic knockout studies. If you knock out ITK selectively, you inhibit the formation of Th17 and Th2 and the resulting cytokines. You don't make IL-4 and 13 and 17 and all those. Interestingly, you're still able to make this Th1 cell. That's a crucial point. Th1 cells are important in fighting infection, rejecting cancers, things like that. It's very important in immune function.
The reason that happens is because the Th1 cell has a redundant enzyme called resting lymphocyte kinase, RLK. The ideal drug, and what Corvus was successfully able to do, is to make a drug that just blocks ITK and spares RLK. The story gets more interesting. In the last few years, several laboratories, including our own, have definitively shown that ITK also plays a role in switching or regulating the balance of what are called Th17 and T regulatory cells. These cells are plastic. They can differentiate back and forth. When you block ITK, genetically or with soquelitinib, you shift it to Treg. What's a Treg? A Treg is the brake, suppresses inflammation, suppresses immunity. For decades, people have been looking for ways to boost Tregs to fight autoimmunity, because you want to suppress autoimmunity. Let's put this together.
Why are we excited about soquelitinib? Well, it has the potential to block Th2 cytokines like IL-4, 5, 13, 31, Th17 cytokines like IL-17, 21, 22, but also increase these Tregs. Let's compare that to some other drugs that are on the market now, DUPIXENT, RINVOQ, two that I'm sure you've all heard of. They hit isolated cytokines, and that's very good, but inflammation is very complicated. It has many cell types, many different types of cytokines. Blocking a few of them would be expected to cause some amelioration of your disease, but probably not lasting. We have the ability to block many cytokines, but keep in mind, we're only doing this in the T-cell, okay?
The ITK target is only in T cells, and you're not blocking the secretion of these cytokines, but from, let's say, other hematologic cells, like a macrophage or a neutrophil or other things like that, or a B cell or things like that. You have, again, this point about selectivity, but broad in its potential. Why is this important? Well, it means that we could potentially have better efficacy, potentially. It means that we could also potentially have more durable efficacy through Tregs. It also means that you might work in diseases that are resistant to these drugs because it's working by a different mechanism. Doesn't care if you had DUPIXENT, because we're going to block those cytokines plus others. Here's the status of the soquelitinib development pipeline.
As I mentioned, starting at the top there, phase III registration, randomized trial, soquelitinib versus chemotherapy ongoing, interim data late this year, interim futility analysis late this year, final data second half of 2027. Okay. For Th2 diseases, atopic dermatitis phase I data we just reported. I'll review that with you here today. Atopic dermatitis phase II randomized blinded trial enrolling data, third quarter 2027. Asthma study we plan to start later this year. That's a Th2 disease. Th2 cell is very important in asthma. hidradenitis suppurativa, a Th17 disease. We want to expand the opportunity by going into Th17 disease. That study's starting later this year as well. Finally, we have a study going on in collaboration with the NIH, a pediatric disease called ALPS, which I really won't talk about here. Okay, now the opportunity for soquelitinib is very broad.
Because of its mechanism, we can think about Th2-driven diseases. Those you're all familiar with, asthma, atopic dermatitis, eosinophilic esophagitis, et cetera. Targets of many large drugs now. IL-17 diseases, psoriasis. DUPIXENT's great in AD, not so great in psoriasis. Doesn't really work. We have a drug maybe could work in both those diseases or others that are IL-17 driven, like psoriatic arthritis, ankylosing spondylitis, HS, as I mentioned. IL-5 are allergic diseases because we impact IL-5 and eosinophils. Finally, the fibrotic disease, and we recently published a paper in mouse models of systemic sclerosis showing activity in a fibrotic disease. Why fibrotic disease? Those are usually Th2 driven. The opportunity here is very large pipeline in a product. These markets are large.
I think you're all aware as shown on the left of this slide, there's a lot of patients with these diseases, both Th2 diseases and Th17 diseases. The number of eligible patients for advanced therapies is quite large. Currently, the % of these patients that is addressable with an oral agent, as shown in the 2024 circle there, is relatively small. This market's expected to grow to about $170 billion by 2030. Yet the oral component, the number of drugs that will be orally administered to address this market's still only a small %, 10%. There's obviously a large opportunity for growth with an oral agent that addresses these diseases. Okay, we've conducted a phase I trial in atopic dermatitis. Now again, keep in mind we've been working along in lymphoma for a few years now.
In lymphoma patients, we're learning about the effect on their lymphoma. We're learning about their safety. We're learning about the effects on the normal immune cells. We're going, it looks like it could have an effect in Th2 normal lymphocytes, Th17 lymphocytes. Let's start looking at animal models and confirm this. We do that, and we confirm this. We say, interesting. We find atopic dermatitis models we work. We say, hey, T-cell lymphoma, that frequently involves the skin, too. Under a microscope, looks just like atopic dermatitis, so we should go into atopic dermatitis. That was some of the motivation behind that. I used to say when I worked on RITUXAN, which is an anti-B-cell antibody, that autoimmunity and lymphomas, hematologic malignancies are just two sides of the same coin. They're basically both caused by disturbances of lymphocytes.
B cells in the case of RITUXAN, T cells in the case of what we're interested now. Two sides of the same coin. Understand them, you should be able to treat one or the other or both. We've conducted a trial, which is really quickly because it's already been presented. Phase I trial, moderate to severe atopic dermatitis. I would say the key points about this trial design, sequential cohorts, 16 subjects in each cohort, blinded, 28 days of treatment, 3 to 1 randomization. Looking at different doses, 100 mg BID, 200 once a day, same total dose, 200 twice a day. We looked at that data. We said, "Oh, wow. This is really interesting. It looks like it's working." We said, "Okay, we're going to treat now 24 patients, 1-to-1 randomization.
We're going to go with what looks like the most efficacious dose for now because we really want to prove the concept, prove the efficacy. Safety looked great. We added another 24 subjects, shown there as Cohort 4. What we're monitoring, of course, is safety and the usual efficacy parameters of atopic dermatitis, EASI scores, IGA, et cetera. Cohort 4, we did another thing. We doubled the duration of therapy. Cohorts 1 to 3 were only 28 days with 30-day follow-up. Cohort 4, we doubled the duration. Here's what we find. It's pretty simple. For Cohorts 1, 2, and 3, where we increased the doses, 28 days of treatment, you have an increasing response measured by EASI-75 and IGA zero and one. Goes from 25% to 33% to 50%. Placebo background was zero.
People ask me, "Why is placebo zero?" Well, we only treated patients for 28 days, that's a short time. Placebos are bouncing around, there's less of a chance to hit EASI-75, we actually enroll sicker patients, I will go over that in another slide or two. We had a sicker population, which also reduces your placebo effect. When we go to eight weeks, shown on the right, new group of patients. Eight weeks get a higher response, higher EASI-75, IGA zero, et cetera. Okay. Let's just look at all the data, just for simplification. Nobody excluded in this data. Okay. On the left is all the patients, not even the best dose. All the patients. Some treated four weeks, some treated eight weeks. Okay. Cohorts 1 to 3, four weeks. The last cohort was eight weeks.
You can see a pretty big, substantial difference between placebo and Cohorts 1 through 4. No cherry-picking, all the patients. Okay. Actually statistically significant, although we didn't power it for that. Again, this was a phase I exploratory study. On the right, it gets interesting. We allowed you to have prior systemic therapy before you came on our study. You had to have a washout period. You weren't on it when you came in, you were allowed to either have failed it, been unresponsive, or at least have received it. Most studies exclude those kinds of patients. When you look at that data, that's 35% of our patients on the right, the response rate to soquelitinib about the same. Didn't matter if you had prior biologic. Remember, I told you it shouldn't matter mechanistically, we expected that. Look at the placebos, worse.
What does this prove? It proves something that's pretty obvious, which is sicker patients do worse. The placebo is worse, and that's what this data shows. What's really interesting is there were several patients on this trial who didn't just receive a prior therapy. They were growing through it. They were failing it. They were not responding. They were totally resistant. Those patients have a washout period, get randomized to our trial, get soquelitinib or placebo. Here's what happened, and you can see their prior therapies, DUPIXENT, methotrexate, JAK inhibitors, RINVOQ, et cetera. These guys didn't respond to that. I mean, didn't respond at all. Okay. They come on our study, the % EASI change, EASI 91, EASI 96, EASI 27, 29. That guy didn't do so well. Look at the two placebos. They come in a flare right away, as expected. They're failing their existing therapy.
They come on your trial and get a placebo. Of course, they continue to grow. This is your perfect controlled experiment, so to say. This proves the point or supports the point I made earlier that this drug will work in patients who've had prior therapy or those who are even non-responsive to that prior therapy. What about durability? I talked about these Tregs. These Tregs are really important. They're antigen-specific cells. It's not like you're immunosuppressed to everything. You're only suppressing the particular inciting antigen, the T cells that are responding to that antigen. This looks at Cohorts 1 to 3 on the left. Right at the end of treatment, week 4, you can see the blue is EASI-75 at the end of treatment.
The hatched bars are the IGA zeros and ones, you can see 30 days, 60 days, 90 days, there's no deterioration of the response. If anything, it got a little better. They're on no treatment then. They're still blinded. The doctor and patient are still blinded. They don't know what you got. We go to Cohort 4, where we only do 30-day follow-up. Same story. The eight weeks of treatment, the blue bar is higher, as we showed before. The IGA zeros and ones are higher, 30 days later, it's unchanged. There's no diminution in the response. Let's compare that to what you would expect. This is a really important point because people are saying to me, "Why didn't you follow these patients longer?" Well, because we didn't have to. Because it was pretty clear.
If you look on the left, what I'm showing here is data from Cibinqo phase II-B trial. The bottom two curves are the approved doses, 100 and 200 mg. You can see that the EASI curves come down. They plateau at around six weeks. They're stable. You stop the drug. This was part of their protocol. Stop the drug, and within one week, the disease is coming back. Two weeks, it's back more. That's called rebound, disease rebound. People say, "Well, what about placebo?" At the top, if you can make that out, there's a gray curve there, gray squares. Placebos don't rebound. They don't rebound because first of all, they're not as deep, so it's harder to rebound when you're not as deep to begin with. Secondly, there's nothing to rebound to. There wasn't a perturbation of the physiologic system.
Rebound refers to you did something with a drug. The body compensates, you take the drug away, and then there's sort of a time for equilibration to resume. Okay. You don't see that with placebo. This is true of all the JAK inhibitors. Controls the disease, rapid rebound. It's true of DUPIXENT. DUPIXENT as shown on the right, there's that % improvement on the y-axis. In this study, this was their phase III trial. They take patients who respond, DUPIXENT phase III trial. That was the approval. You only need to do that part of it, and we'll only need to do that part here. You get approval for what you did at, this was 16 weeks of therapy. We'll do 12 or 16 eventually. They randomized because they were testing a few things. They randomized to different maintenance programs or to placebo, no treatment.
Look what happens. Placebos fail, and they fail in four weeks. You needed rescue meds in four weeks. By eight weeks, it's clear. Now, don't forget, an antibody circulates around a little bit longer than a drug. There's some lag in there. Your rebound happens right away. Every drug, pretty much every drug, is associated with rebound, and it occurs in four weeks or less. Okay? Four weeks or less. As we're doing our trials, we're saying, "No, we don't need to follow people for 90 days." We'll do that in our phase II and phase III.
It's pretty clear if you go beyond four weeks, if you're at four weeks and you haven't seen any rebound, and you have Tregs going up with it, which becomes a really good marker for us, you're pretty confident that you're going to avoid relapse, at least for some period of time, and you're going to have a more durable effect. Okay, now what about the other things? What about the biology here? Well, the biology is pretty consistent. I'll go through this quickly. All these slides are on our website. If you read our press release in the SID meeting, it goes through all this stuff very carefully. Very quickly, on the left here, Th2 by placebo dose and doses, we see a reduction. Each dot is a patient in the circulating Th2 cells. That asterisk up there is really important.
Those are what are called Ki-67 Th2 cells. They're proliferating. Those are the ones that are activated and responding to whatever the inciting agent is. Again, the specificity here is really critical. The middle and right panel show the effects in cohort 3 and 4 on IL-4, 5, 13, and TARC. IL-4 and 5 and 13, we expect that to come down, and they do. They do come down. What's really interesting is it keeps going down in this drug-free period. After we stop the drug, we follow these patients for another 30 days, and these markers are still dropping. By the way, their disease was still getting better, and they were stable, and so forth. That effect, again, of the Tregs and the persistent effect beyond the life of the drug in the body is really of interest.
TARC also dropped in the drug-free period because patients were getting better. TARC is not a target of ITK inhibitor. I want to address that. TARC is made by epithelial cells. We don't do anything to epithelial cells. We do things to T cells. Okay? Indirectly, epithelial cells are affected. By the way, JAK inhibitors, which is a very good treatment for AD, as you know, they're approved. JAK inhibitors do nothing to TARC, yet it's one of the most effective things. TARC is not necessarily a good measurement of what our drug is doing or what other drugs are. It's very dependent on what your mechanism is. Now is, I think, the crucial part of the story. Here we are able to measure Tregs in the blood using some very sophisticated flow cytometry techniques.
Basically, this is looking at placebo and soquelitinib-treated patients. On the top is cohort 3 and 4. On top left is 28 days on the drug for cohort 3, 28 days on the drug, cohort 4. On the bottom is 30 days after you've stopped the drug. 30 days after you stopped the drug in cohort 3 is 30 plus 28 is 58 days. In cohort 4, that would be 86 days after we started the drug. In both cases, you see a very substantial increase in these T reg cells, both at the time you finished your treatment, the last day of treatment, and then 30 days after you've stopped the treatment. These T regs are persistent, is the point.
This explains the durability and the fact that you're seeing a continued suppression of these immune responses that I discussed in the prior slide. The Tregs are at least there for that period of time. What about the others? We know these patients are getting better. What about the other inflammatory things that maybe many of you are familiar with, JAK-STAT, STAT6, and those sort of things? All are important. Well, one of the things that became glaring to us in the data was we were having this upregulation of something called SOCS3. That's not one you're very familiar with, but it's well-known in immunology. SOCS3 stands for suppressor of cytokine signaling. It is a negative feedback to the JAK-STAT pathway. Too much inflammation, SOCS3 goes up, shuts down JAK-STAT signaling. This is well-established. We see that treatment with soquelitinib increases SOCS3.
Increases it, SOCS3 down-regulates, inhibits JAK1 signaling and STAT6 signaling. On the right is just more granularity on those findings. You see SOCS3 going up in Th2 and Th17s, Th1s it goes up a little as well. Interestingly, there is an effect on STAT6. Pretty good effect, 10 to the minus 15 P value between what it was at day zero, Sorry, at the pre-treatment baseline and at the end of treatment, there's a reduction in STAT6. Here's the really important point. It's only reducing STAT6 in the T cells, in the Th2 cells, not in your B cells, not in your myeloid cells, not in your macrophages, not in your kidney cells, not in your liver cells, not in your cerebellum or other places where STAT6 is. Okay? It's only in the T cells, because we're not hitting the STAT6 directly.
This is happening through the effects of the downregulation of the immunity, the resetting of the immunity with ITK inhibitor. We have a pretty good effect on JAK-STAT signaling. Is that a surprise? Not at all. You look at the patient, you know he has less inflammation. None of this is surprising or inconsistent. Now let's talk about safety. There are no safety signals from soquelitinib at this point in time, and we have this over hundreds of patients now with T-cell lymphoma who are sick. They're really immunosuppressed at baseline. They've had a lot of chemotherapy. Their disease is rampant, and they're older, they're fragile, and we don't have any problem in them with soquelitinib, which is why it's in registration phase III trial. We have seen no safety signals either in our AD study.
No serious AEs as shown on this slide in the granular detail here. We group cohorts 1 to 3, that's four weeks of treatment, cohort 4 separately, that's eight weeks of treatment, twice as long. Basically, the incidence of Grade 1, Grade 2 AEs, and they're all mild in both placebo and active, is 41.7% in both. Exactly that. I'm sorry. It turned out to be exactly the same in both of those groups. Really, there's nothing that stands out here. There's no adverse effects on liver function tests, hematologic parameters, kidney parameters, et cetera. So far this drug has a very, very clean safety profile. Okay, now what are we going to do? Going forward, phase II trial, enrolling patients now, open. Pretty straightforward. Same eligibility, moderate to severe AD. We're allowing up to 40% of patients to have had a prior systemic therapy.
We have to cap it, otherwise we'll have 100% because they'll put all these patients on our trial, and we want to have a balance. There's 200 patients that are planned to be enrolled, randomization equally into one of four arms, 200 mg once a day, 200 twice a day, which is the dose we're using for lymphoma, 400 mg once a day, placebo. 12 weeks of therapy. That's longer than the eight weeks we did, so we haven't done 12 yet. 90 days of follow-up. Some people say, "Oh, well, the lower dose may not work." Well, we haven't done lower dose yet for a longer treatment period, so it could work if you treat it longer. The usual endpoints here, EASI scores, IGAs, safety, of course. Data from this trial, third quarter 2027. Okay, now interestingly, we have a partner in China, Angel Pharmaceuticals.
I am the chairman of the board and CEO of Angel Pharmaceuticals in China. We control the board of directors. We own 46% of the company. We licensed soquelitinib for China only to Angel Pharmaceuticals. We really run and monitor the trials in conjunction with them. They have about 35 employees. Their trial is meant to complement ours. We can use their data for regulatory files and vice versa. Their trial, which is also now enrolling at several really good medical centers in Shanghai and other major cities, other major hospitals in China, is enrolling, as shown here, 100 mg BID. We've done that dose. People say, "Oh, that's a lower dose," but it's 12 weeks of therapy. Okay, 200 once a day and placebo. Placebo is blinded. They look at the data.
The data from that part of the study will be available before the end of this year, before the end of 2026. It rolls into the cohort 2, which is another 24 patients with higher doses, 200 milligrams BID and 400 milligrams once a day. What is this examining? It's examining once-a-day dosing. It's examining 12 weeks of therapy. It's examining a Chinese patient population. Well, what do I expect? I expect them to have data that's consistent with ours. That's the first point. More patients, more confirmation of safety and efficacy. There's also another interesting twist. It's well reported in the literature that Asian patients with AD have a greater proportion, a greater component of TH17 disease. That's why they don't respond as well to DUPIXENT. Okay, they have a greater component of TH17. That's good for us because we block TH17.
That's another thing that we're expecting out of this. When they finish that part of it automatically rolls into another 60 to 90 patients, dose to be determined based on the first part of the study, sort of a phase II trial, basically. Placebo-controlled. What's the development pathway for us? Development pathway for us, very straightforward. It's just like everybody else. We did a phase I trial just like everybody else. We're doing a phase II, as I just described. Placebo, active, 12 weeks of therapy, EASI scores, IGA. You don't need to follow patients, that's not part of the ultimate development strategy for approval. Phase III will be the same thing. We'll pick our dose, we'll have 12 or 16 weeks of therapy, yet to be determined. You'll look at the EASI scores and IGAs. That's your approval path.
Other things like maintenance and all that other stuff, that comes later, post-marketing. I'm sure there'll be a lot of interest to do that. Oops, sorry. Okay. I want to say one quick word about our phase III trial in lymphoma. This trial is enrolling. It's a 150-patient trial, one-to-one randomization, chemotherapy versus soquelitinib, PFS endpoint. We do allow crossover because patients want the drug. They want to cross over, but they have to progress first. The interim analysis, futility analysis by the end of this year. The upcoming events for us are start our HS trial second half of 2026, start our asthma trial in second half of 2026, data from the Angel trial in late 2026. That's an important event for us. Okay.
Let me close by saying the key messages for us is that our phase I AD study is as good as any efficacy data you're going to see out there, in my opinion. The safety so far, although early, is very good. We don't see infection. We don't see any evidence that will be a complication. Right now we think we have a very unique drug that has shown efficacy not only in lymphoma, but is also showing efficacy by a very novel mechanism that we understand really well in atopic dermatitis. With that, I don't know if we have time for questions. I think we don't, but I really appreciate your time so late in the afternoon. Thanks.