All right. Welcome, everyone, to Jefferies 2025 Global Healthcare Conference. My name is Roger Song, one of the senior analysts at Corvus Medical Biotech in the United States. It's my pleasure to introduce our next presenting company, Corvus. We have the CEO, Richard Miller.
Thank you, Roger, and good morning, everyone. I want to thank Jefferies for the invitation to the healthcare conference, and thank you all for attending. What I would like to do today is update you on our drug development for Soquelitinib, an ITK inhibitor, especially with our clinical results in patients with atopic dermatitis, as well as set the foundation for what we believe is becoming really a drug development franchise. We will go through some of the data for that. Just to start with an overview, we now look at ITK, selective blockade of ITK, as a platform opportunity, as a new drug target because of the selectivity that has been really discovered by some of the chemistry going on at Corvus. Our lead product, Soquelitinib, has a novel mechanism of action with broad opportunities in oncology, immune diseases, neurology, dermatology, and other things.
The lead drug, Soquelitinib, is in a registration phase three trial in peripheral T-cell lymphoma and also in a phase one trial in patients with moderate to severe atopic dermatitis. This drug is oral and has an established safety profile now in over 100 different patients with lymphoma. Some of those patients treated for up to two years, over two years, with doses three times higher than what we're using in our atopic dermatitis trial. Obviously, the markets for this agent are quite large: cancer, lymphoma, immune diseases. The drug invented by Corvus has issued composition of matter patents in the United States that run until November 2037. The patent has been issued in major countries already. With pharmaceutical extensions, you can expect protection beyond 2040 easily. Now, Corvus has a management team that's done this before.
This idea of blending lymphoma and immune diseases together has been done before by several of the members of my team. Think about drugs like Rituxan, think about drugs like Ibrutinib, and we'll touch on some of those in a moment. It all starts with the target. I've changed my pipeline slide because as I think about this, really the target is the key, as you all know. ITK, which has been known for 50 years or so as a critical target in T-cells, but what hasn't been known is that if you're going to attack ITK, you have to do it very selectively. What I would like to cover with you today is, although there are opportunities in all these areas, pulmonology and fibrosis, gastroenterology, rheumatology, we are currently in the clinic in three main areas: oncology, immune diseases like autoimmune lymphoproliferative disease, and dermatology.
What I'll report on today and update you on is the results from our phase one trial with additional patients from Cohort 3 , as well as tell you something about the effects that we're seeing on Pruritus and our plans for extending the trial and initiating a phase two trial. Let's get back to this strategy of Corvus, this game plan. Early on in my career, we viewed an Anti-B Cell antibody as potentially having a role in lymphoma and immune diseases. Of course, B-C ell depletion has become a foundation of treatment for lymphoma and also for immune diseases. The same playbook was used for a drug called Ibrutinib, which became, as you well know, a top-selling cancer drug. Now there are several BTK products on the market to treat lymphoma and now beginning in autoimmune diseases.
With soquelitinib, a drug that hits ITK, a target in T-cells, the game plan was start with T-cell lymphomas and then move that into immune diseases where T-cells play a role. Of course, that's a lot of immune diseases. Let's review some of the biology or mechanism of what we know about ITK. Let's focus in on the right side of this slide. ITK stands for interleukin-2-inducible T-cell kinase. First of all, it is very limited tissue distribution. It's only in T-cells, NK cells, and another cell called an ILC2. It's a very rare cell, very important in asthma, atopic dermatitis, and inflammatory bowel disease. Very selective target. It's not widely expressed in the body. Why do I emphasize that? Because that speaks to eventual safety.
It has been known for some time, based on studies that were done in the late 1990s, that ITK controls the differentiation of different T-cells. It controls the differentiation of T-cells to what are called TH1, TH2, and TH17, and other T-cells now, which I do not have time to go into. Genetic knockout studies done in the early 2000s from several different laboratories show that if you selectively block ITK, nothing else, you inhibit the production of TH2 and TH17 cells and the resulting Cytokines that come from those cells. You hear about those Cytokines every night: IL-4, IL-13, IL-5, IL-17, IL-31, IL-33, et cetera. I cannot name them all. Now, you still get the differentiation of what is called a Th1 cell. That occurs because the Th1 cell has a redundant enzyme called resting lymphocyte kinase.
As we were thinking about our strategy, we said, wow, this is the perfect target. We can inhibit inflammatory cytokines. We can still permit the development of Th1 cell, which of course is important in fighting cancer and fighting infection. It should not be an immunosuppressive, and our experience tells us it's not. The strategy was to make a drug that's specific for ITK. Now, the story gets a bit more interesting. In the last few years, workers at Janssen Research & Development, workers at Cornell University, Dr. Avery August's lab at Cornell have shown that TH17 cell has plasticity. It can take different forms depending on the microenvironment, the tissue microenvironment. That is under the control of ITK. In what Dr.
August showed and what we've shown in our laboratory now is if you block ITK with our drug or genetically, you skew towards this T regulatory cell, a suppressor cell, FOXP3 suppressor cell. That could be really important. That's the holy grail of autoimmune disease because that could give you lasting or durable effects. We published this in December last year. I won't go through the details. The chemistry, enzymology, et cetera, is in this paper. The drug is shown on the upper left there. You'll notice it's a covalent drug. It has an acrylamide group or a mycotoceptor, same substituents that's on Ibrutinib. We learned a lot. My team learned a lot from Ibrutinib and this family of molecules. If you look on the right, this is called the dendrogram of the kinases, the kinome. There's over 300 kinases in the body.
A drug like Ibrutinib, which is a pretty good drug, well-established drug, that hits BTK, of course, that's what it was made for, and it hits ITK and it hits a bunch of other things, including RLK, which you don't want for autoimmune disease. Look at soquelitinib. It only hits, it only binds ITK. To my knowledge, and I've been working in this family of proteins for 20 years, there is no drug I'm aware of that has the specificity for ITK and acceptable pharmaceutical properties. Over in the middle there is the binding constants, the KDs, the association constants. You can see that Soquelitinib's clean, doesn't hit any of the others.
I think what's really interesting about these family of targets, because again, we're into targets, is that think about this group of proteins that are involved in this ITK, BTK, et cetera list of targets. These are about 11 different proteins that comprise the so-called TEC- family. There are some proteins that you've heard of. You've heard of BTK, that's a successful therapeutic target. You've heard of EGFR, HER2, JAKs. These are all very successful targets. You can now, I believe, add ITK to that list. This has really turned out to be valuable real estate. That's been proven over the last 25 years. Just think about the magnitude and the utility of the drugs for those targets. Okay, using our playbook, our strategy, let's start in lymphoma, bad lymphoma.
We're now conducting a phase three registration trial based on phase one data that gave us a 40% response rate in similar patients with mostly CRs of durations up to two years. Now, this is a disease with a median survival of six months. There's been really no new treatments for this disease in 20 years. There's no fully approved drug for these diseases, the relapsed peripheral T-cell lymphomas. I won't go through the details of the trial, but this trial is now open in four countries and is enrolling. It will enroll 150 patients, randomized equally one-to-one, 75 in each arm, to monotherapy with Soquelitinib versus the standard of care, which is either pralatrexate or belinostat, which are intravenous, inconvenient, very toxic drugs. The endpoint of our trial is progression-free survival, very standard endpoint.
We will allow crossover in patients who progress on the control arm, of course. This is really a pretty interesting phase three trial. Think about this. The median time to progression in the control arm is about three months. It's pretty short. Also, it only takes 150 patients to have a power of 90% to show about a one and a half month improvement, which would give you a hazard ratio of about 0.6. This is a very manageable phase three trial. For this really is an unmet need. There is no treatment for this disease, fatal disease. Along the way, we're validating, again, back to our strategy, patients with T-cell lymphoma have normal immunity, normal immune cells too. We can look at their T-cells and their lymph nodes and their skin and all this other stuff.
Now, one disease where we've seen a lot of activity is so-called cutaneous T-cell lymphoma. T-cell lymphomas in general, not just the cutaneous T-cell lymphomas, have a high propensity to involve the skin. We've known that as oncologists for decades. They like to go to skin. Now, cutaneous T-cell lymphoma is a TH2 lymphocyte, often makes the TH2 cytokines, so it becomes a really interesting model for immune diseases. You can see this patient who failed chemotherapy, who has what's called transformation of CTCL, bad disease. That's fatal. All the CTCLs are basically 100% fatal. This is your worst nightmare of atopic dermatitis. It's not atopic dermatitis, but it's the malignant counterpart. Here's an example of a patient who failed a bunch of stuff, took our drug, had slow regression of skin disease, complete clearance of bone marrow and circulating tumor cells, and reduction of lymphadenopathy.
This patient's been on treatment with 200 milligrams b.i.d. of our drug for over two years now. Our study actually doesn't allow you to go more than two years, and we had to get an exception for her because her doctor and the patient don't want to stop this. Okay, with the escalating data that we get from our patients, animal studies, in vitro laboratory studies, we begin to see a picture that, wow, we can block a lot of the cytokines and a lot of the functions that are important in immune diseases. We have a drug, oral drug with a potentially really interesting mechanism of action. Unlike something that blocks just IL-4 or 13 or IL-5 or this or that other thing, inflammatory disease is really complicated. There are probably hundreds of cytokines.
If you really want to have a big impact in the disease, and we want to have a big impact in the disease, then you really want to hit a more fundamental or a more upstream mechanism. That's the thinking that went into using our drug in autoimmune inflammatory disease. What's the opportunity for us? Because we hit a lot of different of these cytokines. TH2-driven diseases for sure. I just showed you an example of that. Asthma, atopic dermatitis, et cetera. IL-17, okay, driven diseases. Psoriasis, psoriatic arthritis, ankylosing spondylitis, et cetera. IL-5-driven diseases, allergy, fibrotic diseases. We have a paper next week at Euler meeting in a mouse model of scleroderma, for example. Very active in that model. The markets, of course, are very large for atopic dermatitis. There is interest in an oral agent that's safe.
I will not go through the details here. The people in this room are quite familiar with this, but this is a potentially $30 billion market, and only a small percentage of patients now with moderate to severe disease are being addressed. What physicians want, and I have been talking with these physicians now, oral compounds, safe, durable activity. Nobody likes to take a drug forever, okay? Cancer, different. Benign diseases, you do not want to take a drug forever. Okay, we have been conducting a phase one trial as outlined in this slide. I will go through the design quickly because I have presented this before. Patient eligibility is moderate to severe atopic dermatitis. You have to have failed either one prior systemic therapy or a topical corticosteroid. Patients are sequentially enrolled into four different cohorts, one, two, three, four.
Sixteen subjects in each cohort, then you go to cohort two, then you go to cohort three, et cetera. The randomization, it's randomized. Patients are randomized three to one. Twelve get the active drug. Four get placebo. Sixteen in each arm. The treatment period is 28 days. That's short. Twenty-eight days. Then we follow them for another 30 days. Fifty-eight days total. The study is blinded. The patient and the doctor don't know what pill they're taking. There's a dummy pill, placebo pill. The company's not been blinded. It's a phase I study, no requirement for that. We wanted to be able to analyze the data and make modifications as if they were necessary. These cohorts are evaluating different doses and schedules. Very quickly, 100 milligrams b.i.d. That's half the dose we use in lymphoma. Then we went to 200 once a day.
We were interested in Cmax because it's a covalent drug, and our work with Ibrutinib and our experience with covalent modification told us that Cmax might even be more important than AUC. That is why we were evaluating that. The third cohort, which I'll update you on today, is 200 b.i.d., same dose as the lymphoma study. That is a doubling of the doses that we studied in cohort one and two. Now, what are we monitoring in these patients? Safety, EASI scores, IGA, and PP-NRS, the itch, other biomarkers as well. Here are the patient baseline characteristics of 48 patients, patients with atopic dermatitis. Forty-eight subjects have been enrolled now and followed. Cohort one, two, and three are shown on the slide. The combined groups are shown on the far right.
This is pretty much standard demographics, I would say, for an adult population with atopic dermatitis. There are a few things to point out. Number one, we have a high proportion of African Americans, 40-50% or so in each of the cohorts. That just has to do with the sites where the clinical testing was done. All the centers, 15 centers, now we have 17 centers, all United States. A couple of academic centers and other dermatology practices. 40-50% African Americans. African Americans are thought to have worse prognosis, worse disease, more difficult to treat. Second thing to point out, you'll notice in cohort three, Cohort 3 is sicker, sicker patients. The mean baseline EASI score, 27-28. In the other cohorts, it was around 18-20. Remember, 16 and above is moderate disease. 21 and above is severe disease for EASI score.
Okay, and then one final point that goes along, is consistent with the sicker patients, is that the patients in Cohort 3 , there were a higher proportion, 40% or more, that failed a systemic biologic, like a DUPE. And I hope we have time at the end to give you some vignettes on DUPE failures and DUPE refractory. Okay, here's the efficacy at 28 days, four weeks. The mean change in EASI score, and I'll show you the curves in a bit, for the cohort one and two, the 100 or 200 milligram total dose per day. I combined those because really the results are very similar, as you'll see from the curves. 54.6, the mean reduction for Cohort 3 , 64.8. Placebo, 34.4, that's combined placebo from each of the Cohorts. That's a 20-30% difference.
Pretty darn good for a phase one study at four weeks, Dupixent-like four week. Okay. Now, EASI 50s, of course. There is a lot of placebos that reach EASI 50. Everybody has seen that. We do not pay much attention to that, although it should be pointed out that almost all of our patients who get Soquelitinib achieve an EASI 50. Now, the crucial endpoints are EASI 75s, 90s, IGA 0/1. You can see in our study, zero placebos achieve those levels of activity, zero, versus 29%, 50% or so in the soquelitinib group. Here are the curves. This is the change in EASI scores over time. Let us go over this a little bit carefully. This is placebo, cohort one, cohort two, cohort three separately.
First of all, I'd like to point out that we did something I think is really crucial and speaks to the quality of the data. We get your EASI score at screening, and then we get it again at baseline. When I say we, I mean the physicians who are doing this blinded. You'll notice that for all the patients, 48 patients, the EASI score at screening and baseline is really pretty flat and pretty identical. That's really amazing, given that there is some subjectivity to the EASI scores. Patients go on treatment for 28 days. You can see there is a reduction in EASI score for placebo. Everybody's been seeing that there is a placebo effect to an oral medication. More placebo effects, actually, with oral medications. You start to, let's look at Cohort 1 and 2 .
Cohort 1 and 2 are on top of each other. It's the same total dose per day. One conclusion from that is QD, BID dose and doesn't matter. Because those curves are on top of each other. That's probably due to the covalent nature of the drug. You'll notice that the Cohort 1 and 2 , you start to see separation at day 20, at day 15, rather, more separation at day 28. Then it's flat. It even goes down a little. I'll come back to that point later. Look at cohort three, the higher dose, the doubling of the dose. Separation now at day eight, more separation at 15, more at day 28, flat, even down a little bit again for the 30-day follow-up out to day 58. Interesting.
Again, day 28 to 58, you're not taking any therapy, but the study is still blinded. Okay, now a couple of other things to point out here, which speak to our strategy. First of all, you'll notice that the curves are still going down. If you look at the curves at 15 and 28, they're still going down. Begs the question, if I continued people on therapy, would it go down further? We had patients, now that the study is over and unblinded, where the docs are saying, "Gee, I wish I could have given my patient more drug because he was improving continuously, and you, Dr. Miller, you made me stop the drug." Of course, we had to stop the drug. That's the protocol. Okay, here's the combined treatment groups, Cohort 1, 2 3 together versus the placebo. Again, you see separation beginning at day eight.
You see good separation at 15 and 28. Again, a little bit more separation over time. Now, the p-value, we never powered the study for this. I'm surprised and encouraged by the fact that we see a p-value of 0.036 at day 28, which is obviously the logical efficacy endpoint that you would use for this study. Now, we find these results to be quite interesting in that a study with a novel agent, although it had much safety and biologic data from our lymphoma study, we find in 48 patients to come up with a statistically significant number at only 28 days to be quite remarkable, actually. Okay, now this is the EASI 75s and IGA 0/1s for placebo. Again, just summarizing it. Again, placebo, zero, zero. Most studies in the literature will show you 10-20%. We have zero.
Perhaps it's due to the shorter follow-up. I'm not sure. Of course, you see a little bit better results with Cohort 2 versus 1 and better with Cohort 3. At the SID meeting a few weeks ago, we only had eight patients out to day 28. I reported five of eight EASI 75s. That's 63% or whatever. The next four patients who got out to day 28, one out of four had an EASI 75. That was an EASI 89, by the way. The number went from 60-something to 50. People are hysterical now, even though the p-value on my curves went from 0.33 to 0.36, really the same. Here's another interesting thing. That curve, that 50% at day 58 is now 75%. That's interesting. Okay. Whoops, went the wrong way here. Okay, regarding safety, this could be very quick.
We saw in the entire study, we really do not see any difference between the cohorts with dosing. There was only one treatment, thought to be treatment-related AE, that was a grade one nausea in one patient. Did not interfere. Nobody interrupted their therapy during the course of the study. Again, we have experience in lymphoma with doses much higher than this given for weeks or months every day. I think that we have a lot of data on safety. Again, speaking to safety, there are two things to note here that I think are critical when you consider a target. It is why CD20 and Rituxan were so successful, I think. Again I mentioned you have a target that has very limited tissue distribution, ITK T- cells, NK cells, ILC2s. You have a drug that is very specific.
That confluence of selectivity and specificity is seldom reached in medicine, I would argue. There are not many drugs that do that. That is why we think we have a potent and safe drug, oral drug. Okay, now I want to report, this is new data I have not shared before. We did collect PP-NRS data. That is the Peak Pruritus Numerical Rating Scale, which is patients have a diary. Zero is no itch. Ten is your worst nightmare itch. This is a very subjective scale. Obviously, different people have different thresholds for what the scoring is. Anyway, it is a commonly used instrument. Look at Cohort 3 That is a dramatic effect. You see a beginning and after one week, you see a drop in that green curve. In one week, that progressive drop. Cohort 1 and 2 were not able to distinguish, dissect out. Here is the interesting thing.
Look at the lower right. That's IL31 biomarkers, serum IL31 levels. There is a difference in the patients who are treated and respond. Look at the dots. Each dot is a patient versus placebo and versus the non-responders. There is a big difference in non-responders. Everybody finds this in their studies. I can show you the same thing for IL33. 31 and 33 are itch. They speak to itch. The data is very consistent. That is a dramatic effect. If you look up at the top, 50% of the patients where we have the data have a four-point or more change in their PP-NRS. That is a dramatic effect. That is usually 20-40%, let's say with a JAK inhibitor after months of therapy, not after one month. Okay, now what are we doing? I'll go through this quickly. We're extending cohort three.
We're going to add another 24 patients, randomize one to one, 200 milligrams b.i.d., same dose. The only difference, same eligibility, same centers. We expect the same patient selection, etc. Everything's the same. The only thing that's changed is we're going to treat for two months now rather than one month. We are doing that primarily inspired or motivated by the fact that those curves are still going down. Even where those curves are now at one month, many physicians would say, "Hey, why are you extending it? That's good enough for me right there." Nonetheless, we want to test that in preparation for phase two. Now, let's just review very quickly what we're talking about here. We have a really novel drug here, a very novel drug. I can't help the fact that it's such an important target.
It works across different cancers and inflammatory disease. It just does. Another drug like that was called Rituxan, by the way. Look at the cytokines that we affect. We have proof of this either in our patients with lymphoma, our patients with AD, animal models, or in vitro. I can tell you with certainty that we block IL-4, 5, 13, 31. We block the TH17 cytokine, 17, 21, 22. We block ILC2s like crazy. I haven't had time to talk about that. ITK expression in ILC2s is the highest in any cell, by far. Not surprising. We have this incredible effect on Tregs. The other things, let's take a Dupixent. Dupixent's a great drug. It's elucidated. It's getting at part of the problem. You have to keep taking it or you fail. Oral versions will be cool to have. That's nice.
We are trying to do something different. We want to be better if we can. We have a new approach where we are hitting multiple cytokines, perhaps more than we know of. If you ask me what I think is the most important effect, it is probably ILC2s and Tregs. Okay, just to summarize, we have shown now in patients with atopic dermatitis that we have a safe, tolerable drug, significant reduction in EASI scores, dose dependency. 200 milligrams b.i.d. looks good. 400 once a day will be great. We can do that. We are just not going to do it right away. We have other trials going on in other diseases where we will explore that. Sustained benefit for more than 30 days. Our extension cohort is now enrolling.
Okay, the key milestone is we expect to have the next slug of 24 patients, one-to-one randomization in the fourth quarter of this year, probably around November of this year. We'll update people on this extension cohort. While in parallel, we're planning our phase two. And that strategy and planning is already underway. Thank you very much for your attention. I think we're out of time, but unless Roger gives me a minute or.