Autoimmune and Inflammatory Disease Conference. My name's Arabella, and I'm an analyst on the corporate access team at H.C. Wainwright. H.C. Wainwright is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 24 publishing senior analysts and over 650 companies covered across all sectors. If you would like more information, please go to our website, hcwco.com. From a logistics standpoint, please make sure you reference the virtual conference online portal that provides your individual links to join meetings and all presentations. With that said, have a great day, and I'd like to introduce Richard Miller, the CEO of Corvus Pharmaceuticals.
Thank you, Arabella. Good morning, everyone, and thank you for joining us on this presentation. I have a lot to cover, so I'll jump right in. My name is Richard Miller. I'm the CEO of Corvus. Let me just jump in. What I'd like to spend most time today is on our first-in-class immune modulatory drug, which is a very specific ITK inhibitor. This drug is now in a phase III registration trial for relapsed peripheral T-cell lymphoma that's enrolling in the U.S. as well as Canada and Australia. This drug is also, because of its biologic properties, in a phase I randomized placebo-controlled trial in moderate to severe atopic dermatitis. I'll spend most of my time this morning going through over that data and what we're anticipating over the next few months.
Recently, we also announced that soquelitinib, our ITK inhibitor, has begun a phase II trial being conducted by the National Institute of Allergy and Infectious Diseases in a rare genetic disease called ALPS, or autoimmune lymphoproliferative syndrome. The pipeline slide, just to review again, this is a drug that's in a phase III registration trial. I'll give you an update on that quickly. We'll talk about atopic dermatitis and what we expect for the remainder of the year, and then talk about a little bit at the end about the ALPS study. Now, we've always been interested in the intersection of lymphoma, which are cancers of the immune system, and autoimmune or inflammatory diseases. My team and I have ran this playbook before. It was called Rituxan. Rituxan is an antibody, of course, reacts with CD20, was developed in B-cell lymphoma, and then extended into various autoimmune diseases.
Same thing with ibrutinib. Ibrutinib is a BTK inhibitor. Small molecule members of my team, including myself, invented and developed ibrutinib, started in B-cell lymphomas, and now extended into autoimmune diseases as well. Returning to this, which in the past successful playbook, soquelitinib interacts or blocks an enzyme called ITK, and we'll go over the details of that in a moment. Because ITK is expressed in T-cells, we start with T-cell lymphomas with the intention to extend beyond T-cell lymphoma into other cancers, solid cancers, as an immune modulator, and into inflammatory or autoimmune diseases. Very quickly, I've shown this many times before, but ITK stands for Interleukin-2-Inducible T-cell Kinase. It is a kinase that's involved in multiple functions in a T-cell. Its tissue distribution is very restricted.
It's only expressed in T-cells and NK cells, and that is one of the factors that I think leads to the safety that we're seeing in both our lymphoma and our autoimmune studies. It was shown 25 years ago by some basic scientists that if you genetically knock out ITK, you block the differentiation of normal naive helper T-cells into Th2 and Th17 cells. You prevent those cells from forming. Now, those are the cells that make cytokines that you've heard about, like IL-4, IL-5, IL-13, IL-17, and others. Those cytokines are involved in a range of autoimmune diseases like psoriasis, atopic dermatitis, and many other asthma, and many other immune diseases. Now, blocking ITK selectively allows the differentiation of the Th1 lymphocyte, which leads to the killer T-cells that are important for rejecting cancer cells and also for rejecting certain infections, especially viral infections.
Now, this happens because the Th1 lymphocyte has a redundant enzyme called resting lymphocyte kinase RLK. Based on my team's experience with Ibrutinib and with kinase inhibitors, we were able to develop a drug that does or recapitulates what the genetic studies showed many years ago in these genetic knockout mice. That is, we were able to make a drug that very selectively blocks ITK but spares RLK. This was published in December. The chemical structure of this compound is shown on this slide. The specificity of binding is shown on the slide, and I won't spend too much time on this. The details of the enzymology, the chemistry, and the immunologic properties can be reviewed in this paper.
Now, more recently, one other aspect of this mechanism that is turning out to be very important was published by a few different laboratories, and we've been able to confirm this in our own lab. Very briefly, ITK is involved in the generation of T regulatory or immunosuppressive cells, cells that can suppress an autoimmune reaction. That occurs when you block ITK. ITK is responsible for a switch from Th17, a pro-inflammatory cell, to a suppressor cell. Some of our coworkers, Avery August at Cornell University, showed that either by genetic knockout or by using soquelitinib, you induce these T regulatory cells, which I believe are going to be turning out to be the most important aspect of this therapeutic modality. As I mentioned earlier, our playbook started in lymphoma, T-cell lymphoma in this case.
I'll go through this very quickly, but T-cell lymphoma is a very bad disease, especially when it relapses. It is not as common as B-cell lymphoma, but it also has no approved drugs in the relapse setting, really no competition, no good approved agents, except for an antibody drug conjugate called brentuximab vedotin, which only addresses a very small part of the T-cell lymphoma market. Yet brentuximab vedotin did $1.6 billion last year. Now, half of that was Hodgkin's disease. The other half was for this subset of T-cell lymphoma. As you can see on the right here, relapsed T-cell lymphoma has a very, very bad prognosis with a median survival of around six and a half months. I'll skip some of the phase I data that we've done. We did your typical dose escalation single-agent study in very refractory T-cell lymphoma patients.
As we refined the dose and the eligibility criteria, we did an extended extension of the study into what we call our phase III eligible patients. We reported this just last week at the T-cell Lymphoma Forum, a meeting in San Diego with T-cell lymphoma experts. The data that was presented there in 23 evaluable patients, you can see the waterfall on the right there. We had nine objective responses, six complete responses, three partial, nine out of 23, 39%, 26% CRs. CRs are very hard to get in T-cell lymphomas. Our CR rate is probably double, is double what you would see with conventional or standard chemotherapy. These responses can be long-lived, as was shown on that swimmer plot. We have had patients on this treatment out to over two years in remission.
With this data, we have now initiated, or several months ago initiated, a phase III registration trial, which is shown here. The design of this trial is patients with greater than one but less than or equal to three prior therapies, and the types of T-cell lymphoma histologies are shown on the left there, the eligibility. PTCL-NOS means peripheral T-cell lymphoma not otherwise specified. That's the most common. The other types there, collectively, this is about 85%-90% of the T-cell lymphomas. 150 patients will be randomized, 75 into each arm to receive soquelitinib 200 milligrams orally twice a day, or either belinostat or pralatrexate, which are two drugs that received accelerated approval about 15 years ago. There is no fully approved drug for T-cell lymphoma. Belinostat and pralatrexate are basically chemotherapy drugs, are given intravenously and have the usual side effects associated with chemotherapy.
The endpoint of this trial is PFS, progression-free survival, and the secondary endpoints are shown there, duration of response, overall survival, et cetera. The study does allow crossover. If you're on the control arm and you progress, so you're an event, then you can crossover to get soquelitinib. The data we presented last week at the T-cell lymphoma Forum showed that we had a median PFS of 6.2 months. For perspective, the control agents are usually one- to three-month published median PFSs. Belinostat and pralatrexate are one to three months. CR rates around 10%, 12%. As I mentioned, we have about 26% CRs, 39% overall response, and PFS of 6.2 months, with a 30% PFS at 18 months and average duration of therapy over 17 months. Our durability looks very good.
Oral agent safety looks very good, and efficacy appears to be superior to the standard of care agents. Just a few quick examples. I've shown this many times. We can see dramatic responses in large tumors. These tumors, by the way, and this is relevant when I talk about atopic dermatitis, they often involve the skin, T-cells that like to go to the skin. Here's a big mass about the size of a football. This patient had a PR in 15 days, went on to a CR lasting for two years. In these cancer patients, we can also monitor the effects on normal lymphocytes and cytokines. As predicted or anticipated by the mechanism of action, we see in the blood and in the tumor changes in normal T-cells and cytokines that you would be expected on the mechanism of action. I won't go through these details.
These slides are on our website, and you can study them more carefully. We are interested in some of these T-cell lymphomas that involve the skin, like shown here, a patient with what's called cutaneous T-cell lymphoma. This is transformed cutaneous T-cell lymphoma. That's a very poor prognostic factor. This patient had failed the usual standard therapies and has been on soquelitinib now for over two years and has had continued slow regression of cutaneous tumors, cutaneous plaque disease, and circulating leukemic cells. Why I like to show this slide is that this disease under the microscope is very, very similar histologically to atopic dermatitis, which is also a disease that involves Th2 lymphocytes. As we were enrolling, as we are enrolling this trial and getting more data, we recognized that there might be applications of selective ITK inhibitor to autoimmune diseases.
This led us to begin to investigate various animal models and leading to a human clinical trial. Unlike other agents or most of the other agents that you've heard about, where, for example, you give an antibody or a drug that blocks a particular cytokine or maybe a couple of cytokines or the receptors, like Dupixent, for example, blocks IL-13 and 4 receptor, soquelitinib's mechanism is upstream, blocking the cellular functions or the cellular differentiation that is responsible for the production of potentially many of these cytokines, as well as other activities like the regulatory suppression I mentioned earlier. The potential opportunity here is quite large. Th2-driven diseases blocking ITK prevents the formation or limits the formation of Th2 cells. The opportunities here are asthma and atopic dermatitis, IL-17-driven diseases like psoriasis, IL-5 diseases like allergies, and even the fibrotic diseases.
We've presented papers at the ACR meeting last year, very nice data in a genetic animal model of scleroderma showing soquelitinib very active in that model. That occurs because Th2 cells are critical in fibrotic responses. The market in atopic dermatitis is quite large. I won't spend time, as I think everyone's familiar, that there's still demand for effective agents, particularly agents that can be delivered orally. That's where we see one of our key advantages. Based on this, we have initiated and are well along now in a phase I randomized trial in atopic dermatitis where we take patients with moderate to severe atopic dermatitis that have failed at least one topical or systemic therapy. The schema of the study is shown on this slide. There are four cohorts that are sequentially enrolled. There are 16 subjects per cohort.
You fill up cohort one, then you go to cohort two, three, et cetera. The 16 subjects are randomized three to one active to placebo. There will be 12 active and four placebo in each cohort. Patients receive either placebo or active drug. They are both tablets, and the tablets are indistinguishable. The trial is blinded. The patient and the doctor do not know what they are receiving. The company is not blinded. We have an outside data monitoring board that is also not blinded. We can evaluate the data as it is being collected. That is fine in a phase I trial. The treatment duration is 28 days. That is rather short. Most AD studies and trials involve months of therapy, three months, six months even, or beyond that.
We elected to do a shorter trial for a variety of reasons, including the mechanism of action, which we thought would result in meaningful activity in a shorter timeframe. That is turning out to be a valid consideration. The different cohorts examined different doses and schedules. Again, I won't go through every detail here. 100 mg b.i.d., 200 mg once a day, 200 mg twice a day, 400 mg once a day. We have completed enrollment and follow-up on cohort one and two. Some of that data was presented at the JP Morgan Conference in January of this year. Cohort three is almost done enrolling, and we'll have the 30-day follow-up on everyone by the time of our next presentation, which is going to be at the Society of Investigative Dermatology meeting on May 7th in San Diego.
We will there report on the data from cohort one, two, and three. In addition to the 28 days of treatment, we have been following patients 30 days beyond the treatment, and now in some cases, cohort one and two, even for one month beyond the 30-day drug-free period. The reason for that is we are gaining confidence that there is a very durable effect, and we want to see how long that effect can be maintained, how long the disease control can be maintained after discontinuing the therapy. Cohorts one, two, and three are nearly done. We'll look at that data. We'll decide about cohort four. We are considering the need for cohort four. We don't think it's going to be necessary given that we're at doses that give pretty good saturation. We have a very good pharmacodynamic marker.
We can measure saturation of the ITK target. Very quickly, this is just a review of what I showed back in January. At that time, we had enrolled cohort one and two. We did not have all the follow-up on cohort two, but here are the baseline characteristics in cohort one and two. Basically, a couple of things to point out. We have a high proportion of African- Americans. They tend to do worse with atopic dermatitis and are more refractory to disease. None of our patients were receiving, although they failed, none of them were on concomitant topical steroids. There was one placebo who was on topical steroids. We had 24 subjects with soquelitinib and eight receiving placebo. The cohort one data, we had longer follow-up, and there are a couple of notable things here on this table. The mean percent reduction in EASI score.
EASI Score is the measurement of efficacy. It's a commonly used measure of efficacy. Another commonly used measure of efficacy is called the IGA Score, Investigator Global Assessment. That's a four-point score. Zero and one means you have zero means you have no disease. One have very minimal disease. Four, you have a lot of disease. EASI 50, for example, is you have a 50% reduction in the score, high score being bad. If it's reduced, that shows improvement. Basically, the mean percent reduction in EASI for placebo was 27%. That's pretty consistent with placebos in other studies, although more recently, that's been creeping up in various published studies. Our active was 55.9%. That's a pretty good score, pretty good improvement. The very interesting thing was that over the subsequent four weeks with no therapy, a couple of the placebos got a little bit worse.
The score dropped to 19.1 because their disease is progressing, whereas the patients receiving soquelitinib had actually gotten some improvement and improved to about - 60. Importantly, what the approvable endpoints and what are clinically meaningful endpoints are, almost every regulatory authority now is requiring this, are the EASI 75s and IGA 0/1s. What you can see here, although the four placebos, two, of course, reach an EASI of 50, placebos can each reach 50 just based on the waxing and waning of their disease that can occur commonly. It is not so common to achieve an EASI 75 or better. In fact, we had zero, whereas our soquelitinib group, 25% or 40% out at eight weeks. Those are pretty good scores. I'll put that in perspective in a moment. Here is a summary of the data we presented on January 5th.
We had about a 30% IGA or EASI 75. Combine the groups together shown on the far right, about a 30% difference from the placebos that were zero. None of the placebos achieved the EASI 75 or IGA 0/1. In most published studies, Dupixent and others, you'll see maybe 10%-15% placebos will achieve EASI 75. Now, regarding safety, we have seen very good safety with soquelitinib, not only in our lymphoma studies now, which have been going on for a couple of years and patients have been taking our drug every day for up to two years. In the AD studies so far, we see basically no clinically significant laboratory abnormalities, no significant AEs, no interruption of therapy. Everyone has completed the planned treatment. Now, just comparing soquelitinib to other agents, soquelitinib is an oral agent, novel mechanism of action.
To my knowledge, there has never been an ITK inhibitor tested in autoimmune disease, certainly not a selective one. We have the potential advantage, as I mentioned earlier, of blocking the production, the cellular production of multiple different cytokines, as well as exerting suppressive functions and other things, as opposed to a Dupixent or some of the other agents, Rinvoq, which is JAK inhibitor, or some of the antibodies, the IL-31 or IL-13. The results so far tell us that soquelitinib may represent a novel medication for autoimmune disease and in particular, atopic dermatitis. It's oral, has a novel mechanism of action, appears safe. We've seen durable and deep responses in patients with moderate to severe disease. I'm not going through the details here, but we've seen cytokine changes in the serum that are consistent with the presumed mechanism of action.
Responses appear to be very durable, and we think that this is going to have potential for a range of autoimmune diseases. We're continuing, of course, to optimize the dose and schedule in preparation for a phase II trial, which we believe can begin by the end of the year. Now, one other autoimmune disease, just to mention really quickly that I want to close on, which we're excited about. There is a very serious autoimmune disease called Autoimmune Lymphoproliferative Syndrome. It's a genetic disease. We showed in a mouse model a couple of years ago that soquelitinib was extremely effective in this mouse model. There is a human equivalent of the mouse genetic defect. It's a disease that children are born with, and they start to get sick when they're about two years old, lymphadenopathy, and a lot of autoimmune problems. There are no good treatments for ALPS.
It's an unusual disease. There are about 2,500 patients or cases in the U.S. They can live into their 30s, 40s, and 50s but have a lot of problems with infection, lymphadenopathy, anemia, and cytopenias, et cetera. We now have a trial going on at the NIH where we're looking at patients who are age 16 and older because we can't go right to children yet. This could be really the first effective or useful drug. Currently, these patients get cyclophosphamide and steroids and sirolimus, other chemotherapy-type agents to control their disease. Milestones coming up listed here really quickly. Atopic dermatitis cohort two data, we've already completed the ALPS phase II trial initiation, atopic dermatitis data at the Society of Investigative Dermatology meeting, cohort one, two, and three. Not sure we're going to need to do four.
Full data set with much longer follow-up later in the year, third quarter. Solid tumor studies starting, I didn't really talk about that in the third quarter, and a phase II trial starting later this year. With that, I want to thank everyone for their attention. These slides are up on our website, and be happy to take any questions if we have time, Arabella or other.
Hi, Richard. Thank you so much for the great presentation. Unfortunately, I don't think we have time for questions.
Okay. That's fine.
We really appreciate the time and effort it takes. Thank you from the team.
All right. Thanks again. Bye, guys.