Hi, everyone, and thank you for joining the 26th Annual Global Investment Conference. My name's Arabella, and I'm a corporate access analyst at H.C. Wainwright. H.C. Wainwright's 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 senior publishing analysts and over 636 companies covered across all sectors. Please visit hcwco.com for more information. We're grateful you're able to join us, and for what is hopefully a productive day of one-on-one meetings, corporate presentations, and panels. With that being said, I'd like to introduce Richard Miller, who is the CEO of Corvus Pharmaceuticals.
Thank you very much. Thank you all for coming today. It's a pleasure to be invited to the Wainwright Conference. I'm Richard Miller, the CEO of Corvus Pharmaceuticals, and what I'd like to do today is provide an overview of Corvus and all the things that are happening, but really focus in on one drug in particular that we're pretty excited about. You'll notice that I have a new tagline on this cover slide here: The power to control the immune system, and I like to think that we now have a drug that actually does have this characteristic, this feature, and I hope that as we go through this presentation, you'll, you'll come to realize that, so let me just start with an overview. We're developing first-in-class immune modulators with broad opportunities in cancer and immune diseases.
Cancer and immune diseases, lymphomas, the cancers that we focus on really are two sides of the same coin. Cancer, lymphomas are cancers of the immune system, and inflammatory diseases are really the other side of that coin. They're closely related. So I wanna start with our ITK inhibitor platform opportunity. When we first started making ITK inhibitors, we thought that this was a drug. It is a drug, but it's more than that. It's a platform. It's a technology that allows us to modify, modulate different components of the immune system. So soquelitinib is our lead molecule. It's a covalent, very selective inhibitor of ITK. The word selective or specific is really crucial here, because if you're not specific, then you get other off-target effects that really you don't want.
So we've now validated soquelitinib in our lymphoma studies, which support not only its potential application in T-cell lymphomas, but also a variety of other immune-related diseases. This morning, we had a press release that announced the start of a randomized registration clinical trial, phase III clinical trial in relapsed T-cell lymphomas, and I'll go through that story with you. That's a registration trial. Now, along the way, what we learned about this drug is it has very important, powerful effects on modulating immunity, and it has applications in a variety of immune-related diseases, and I'll go through those diseases later. Everything from dermatologic diseases like atopic dermatitis to allergic diseases like asthma, inflammatory bowel diseases, fibrotic diseases, et cetera.
This has resulted now in us performing a phase I randomized trial in atopic dermatitis that's enrolling, and we'll have data from the first couple of cohorts in later this year. So this is a novel mechanism of action, a novel immunotherapy that has applications across many disease areas: cancers, even solid tumors, lymphomas, hematologic cancers, and autoimmune and inflammatory diseases. Now, we're very aggressive about intellectual property. The composition of matter patent for soquelitinib is issued in the United States and most major countries. It runs until November 2037 , without, not including pharmaceutical extensions, which will certainly be available to us. There are a host of second- and third-generation compounds that are patent and more recent compounds, and we have a bunch of patent applications that deal with methods of treatment, monitoring, skewing the immune response, et cetera, et cetera.
Now, I'll focus mostly on the ITK platform. Again, I'm using the word platform, but keep in mind there are a couple of other drugs that we have coming along that also work to modulate the immune system. One I'll talk more about later, called ciforadenant. This is just our pipeline slide. As I mentioned, soquelitinib is now enrolling in a registration phase III in peripheral T-cell lymphoma. We expect to start a solid tumor trial later this year. The first tumor will be kidney cancer, and as I mentioned, it's rolling along now in an atopic dermatitis randomized placebo-controlled trial. Now, let's talk a little bit about the mechanism of action. ITK stands for Interleukin-2-inducible T-cell kinase.
It is a kinase that's expressed in T-cells and NK cells, and a cell that you may never have heard about before, but it's turning out to be really important, called an innate lymphoid cell. That's an important cell because it lives in your skin, your gut, and your lungs, and is involved in a lot of inflammatory cells, and it's the most highly expressing cell of ITK. Now, ITK is involved in T-cell receptor signaling, similar to the way BTK was involved in B-cell receptor signaling. My team developed ibrutinib, so it was a natural extension to now move over to the T-cell side. Now, less well appreciated was that ITK is fundamentally involved in the differentiation of T-cells. So T-cells are a family of different kinds of cells with different functions, and they can have different flavors.
But the ones that are most known to you would be called TH1, TH17, TH2. Now, TH1 cells are involved in rejecting tumors, fighting off viral infections, and certain other infections. TH2 and TH17, you've heard about those because they make things like Interleukin -4 and 13 and 5 and 17. Those are the diseases that you've heard of associated with, or diseases such as psoriasis and asthma and atopic dermatitis, etc. Now, it was known twenty years ago that if you knock out ITK specifically, you block TH2 and TH17 and the resulting cytokines, but you still allow for TH1. Why does that happen? That happens because the TH1 cell has a redundant enzyme called Rlk, resting lymphocyte kinase.
Corvus and its clever chemistry and biology group said, "Okay, I need to make a drug that hits ITK but spares Rlk." Then you could get that. You wouldn't get immunosuppression, you'd be able to reject tumors, you'd be able to fight infection, but you might block those cytokines that are responsible for inflammatory diseases. Very hard to do that. Only one amino acid difference in the binding pocket of Rlk and ITK, but we succeeded. That's been published, the structure has been published, and you can look all that stuff up. Now, the first disease that we decided to work on was T-cell lymphoma. Why? Because we kinda did that with Rituxan. We worked. We started with lymphoma and moved into autoimmune disease. We did that with ibrutinib, started in lymphomas, CLL, moved into autoimmune disease later.
And so lymphoma becomes a very good testing ground. Serious disease, people can die. Single phase III trials get you an approval, high pricing. Learn a lot because people with cancer also have normal immune cells. So let's talk a little bit about T-cell lymphoma and the registration trial that started today. Bad, bad disease. As you can see on the right, once you relapse with T-cell lymphoma, the median overall survival is six and a half months. That's pretty short. That makes lung cancer look good, and that ain't good. Notice how fast that Kaplan-Meier curve drops. I mean, 50% drop in the first couple of months. Okay, now, the treatment for peripheral T-cell lymphoma is usually something called CHOP or CHOEP, but basically chemotherapy.
Almost everybody will relapse within the first five years, mostly within the first couple of years, and then they're a candidate for all kinds of experimental things. Now, there's one drug that's approved, fully approved for peripheral T-cell lymphoma that I wanna mention, called Adcetris. It's an antibody-drug conjugate. It's Seattle Genetics, now Pfizer. That did $1.6 billion, actually $1.8 billion last year in global sales, $1.8 billion. Let me tell you, half of that was Hodgkin's disease, so that doesn't count 'cause that's a different disease, but the other half is T-cell lymphoma. But it's only the T-cell lymphomas that express CD30, which is maybe, if I'm generous, 20% of T-cell lymphomas, probably more like 10%.
But the point is that the market for this drug, for an effective drug in T-cell lymphoma, could be very, very significant. Most of these peripheral T-cell lymphomas, 80%-90%, are CD30 negative, so brentuximab vedotin would not be useful. Okay, so we've conducted pretty comprehensive single-agent studies with soquelitinib in relapsed peripheral T-cell lymphoma, and I'm gonna give you the most recent data on the expanded cohort, which has the same characteristics as our planned phase III trial. So we have 23 patients that have enrolled on this trial. One to three prior therapies. They had to have at least one prior therapy, no more than three, and that has to do with the fact that we require that you have some degree of immune fitness or immune competence.
Now, you'll notice, if you look at the right, that's a very nice-looking waterfall plot for a disease that is this bad. There are nine objective responses out of the 23 evaluable patients. Six of the nine are complete responses. In order to be a PR, by the way, this is Lugano criteria, you need to be 50% reduction in tumor mass. So, it's a very high CR rate, okay? Unprecedented CR rate, I would say, although this is a small group of patients. Now, the follow-up here now on some of these patients is a couple of years. We've had patients on this drug for up to two years. We stop at two years because we can't go longer because of the protocol and regulatory requirements. So let me put this in perspective.
There are currently two drugs used for relapsed peripheral T-cell lymphoma. I'll go through this really quick. Belinostat, pralatrexate, they were approved about 15 years ago. Accelerated approval, not a full approval. They were approved on single-arm studies based on response rate, around 120 patients. The confirmatory trials have never been done for those agents. In fact, in November last year, the FDA held an ODAC meeting, basically admonishing the company for never doing the trial, considering maybe taking these off the market. They didn't take it off the market because there's nothing else really for patients. Now, how do we compare? Obviously, smaller number of patients. Comparable patients, though. We have a response rate of 39% with, again, 26% CRs, which is about more than double the CR rate seen with belinostat and pralatrexate.
The PFS, which is going to be the primary endpoint of our phase III registration trial, over six months, compared to one point six and three and a half months. Pretty short, meaning that a phase III trial is short because the control arm is only a few months median. Now, the important thing is safety and convenience. Belinostat is given IV for five days in a row every three weeks. When you only have six months to live, that's kind of a pain. And pralatrexate is given weekly. They're basically chemotherapy agents with usual myelosuppression, mucositis, things like that. We've really not seen any of that. We've not seen any hematologic, renal, hepatic, any toxicity whatsoever. Now, you'll see I listed pruritus there. That's really because many of these T-cell lymphoma patients have disease in the skin.
T-cell lymphomas are a disease that like to go to skin. Think atopic dermatitis when I get to that. But for some reason, these T-cell lymphomas love the skin. They home there. So anyway, some of this, all of it is really due to progression in some of those patients, not a side effect of the drug. Let's look at what some of these tumors look like. So this is T-cell lymphoma. This is a patient who had failed a bunch of prior therapies, called PTCL NOS, the most common kind, peripheral T-cell lymphoma not otherwise specified, NOS. CHOEP, GDP, HDAC inhibitors, anti-PD-1s failed, had circulating tumor cells. They frequently have circulating leukemia cells in their blood, lymphadenopathy, splenomegaly, and a big mass about the size of a football on her chest, on her abdominal wall, rather.
You can see within two weeks, there's been a tremendous response, regression of that tumor. That's a PR at that point. This patient went on to have a CR that lasted for two years, and then we stopped the drug. Okay, now, the interesting thing is that, as I mentioned, why we study started in lymphoma, we can look at the normal cells, and we can look at the tumor cells. When we look at the blood of a patient like this, we find a decrease in these TH17 cells. Remember what I told you, mechanism, you block TH17. You find an increase in these TH1s. Remember I told you, you get skewing or you don't, you don't harm the TH1s. Look over at the top right. IL-5 and eosinophils drop.
Frequently, these patients will have eosinophilia because their T-cells are just not working right. And you can see that from the normal cells, we drop the eosinophils, we drop the IL-5. IL-5 leads to eosinophilia. IL-5, think asthma, think allergy, think diseases, think atopic dermatitis, think things like that. So this is what we learned by studying the lymphoma patients. I like to think back to Rituxan. Rituxan, of course, eventually got approved for rheumatoid arthritis and a lot of different skin dermatologic diseases, but all that was learned by these lymphoma studies. The bottom just shows similar things happening in the tumor. We get an increase in these TH1 or killer cells that destroy the tumor, and that's the mechanism of action. Here's another patient, same thing, failed a bone marrow transplant. That's bad lymphoma.
When it comes back after a bone marrow transplant, started on soquelitinib, CR lasted twenty-five months. Now, here's a disease I show for two reasons. Two reasons. One is different histology. I wanna describe to you that we're seeing activity across histologic variants, across histologies, different diseases. They look different under the microscope. They act differently clinically. But this disease in particular, called cutaneous T-cell lymphoma, sometimes called mycosis fungoides, is a disease that's the quintessential TH2 lymphocyte. Remember back, I told you about TH2 cells being blocked. So this is, think of this as like your worst nightmare, atopic dermatitis. In fact, some patients with mycosis fungoides or cutaneous T-cell lymphoma are often misdiagnosed as having atopic dermatitis and vice versa. In fact, there are two papers published by others showing that patients on Dupixent develop mycosis fungoides.
I'm not saying Dupixent causes mycosis fungoides, but it's a misdiagnosis and probably, although that's still debated a little bit. Anyway, as you can see, here's these red blotches on the skin, really all over her body, and marked improvement in a couple of months. This patient has had continued regression of this disease over a year now. But the point here is that these are the same very similar cells to what you see in atopic dermatitis, except these are malignant, so they spread in the body. Okay, so this led to a phase III registration trial, which is outlined here. So the eligibility here is relapsed or refractory peripheral T-cell lymphomas. That is what these called. The exact types of lymphomas are indicated there. I won't go through those details. One of them is a disease called AITL, angioimmunoblastic T-cell lymphoma.
Again, that's a disease where we've seen very good responses, and it's really, really similar to what you see histologically in atopic dermatitis. Very similar. So patients have to have greater than at least one prior therapy, but no more than three. Prior therapy means cytotoxic chemotherapy. They get randomized. 150 subjects will be randomized one to one to either soquelitinib, 200 milligrams BID, or standard of care, physician's choice of belinostat or pralatrexate. We allow the physician to choose. Really, the results with either are pretty similar. The primary endpoint is PFS, progression-free survival. Secondary endpoints are shown there, OS, duration of response, overall survival, sorry, response rate. So we do allow crossover, which we feel will accelerate the enrollment in the trial.
'Cause patients want the new drug, they don't want the old drug. Patients come in, they say, "I want that drug. I don't want the ones that are pralatrexate ." And so this way, they say, "Well, the only way you can get the new drug, come on the protocol. You either get it now or you get it later." Obviously, when they cross over, they're already an event. They have to progress, and they have to still be eligible, and you can't be. You still have to have some basic eligibility criteria, functioning liver and kidneys and all that sort of stuff. So, this trial started already.
As I mentioned, 150 patients, not a large trial, but the statistics on this shows that we have about a 90% power to show an improvement of one and a half months above three months, which is the expected control. Okay, and that'll give you a hazard ratio for the statisticians in the audience of around 0.56. It's a very good hazard ratio. Why did we pick that? Because that's clinically meaningful. I'm a lymphoma doc, and, you know, you see protocols now with, you know, improvements of, you know, a week or so, and it's not really clinically meaningful. We wanted something that would get people's attention. So this trial is gonna enroll now at 40 to 50 centers. Not all 40 or 50 are open yet.
Predominantly United States, but also centers in Canada, Australia, and South Korea. South Korea has been very good, a few centers there for us. Okay, now, I mentioned that we're interested in solid tumors. This TH1 biasing, it's called, led us to study this in a variety of solid tumors in animal models. We've presented that at the AACR, and it's active in almost every animal model we look at, tumor model. And so together with the Kidney Cancer Research Consortium, we're planning to start a phase I, phase II trial in relapsed, IO relapsed renal cell cancer later this year, where soquelitinib monotherapy will be given. That is soquelitinib alone till they progress, and then we add a PD-1 to it, and that's based on some animal models that we've looked at.
So this is really exciting because activity in this setting, which we'll be able to see, because there's a monotherapy part of this, would be really very dramatic and revolutionary in terms of a new approach to immunotherapy. Okay, so now let's back up again. The parallels here between rituximab and Ibrutinib are pretty clear. rituximab and ibrutinib started thinking about the key elements of the immune system, demonstrating value in lymphoma, activity in lymphoma, moving into inflammatory diseases, and then, of course, broadening into a variety of inflammatory diseases. The same playbook, the very same playbook, is being used for soquelitinib. Of course, here we have to start in T-cell lymphomas because the target is in T cells, not B cells. Okay, so this leads us to immunology, inflammatory diseases.
So I mentioned that we block TH2 and TH17 cells very well. And so that means, and we have shown, and we have published, that we're blocking the production of a lot of different cytokines: IL-4, IL-13, IL-5, IL-33, IL-31. I can't remember them all. I'm sure I forgot a few along the way. IL-17, that's an important one. Now, if you think about the competition here, let's take Dupixent, a great, great antibody therapy. That blocks IL-13 and IL-4. Doesn't block IL-5, for example. Or let's take Nucala. That blocks IL-5, doesn't block IL-4 and IL-13. So the immune system is a wily beast, and it has a lot of different ways to get around you.
And so we think that we might have a more effective agent because we're gonna block the site of production of numerous cytokines. Importantly, we don't just block T cells because we allow, in fact, we provoke, in fact, we induce this TH one skewing, which is really the important cell for infection. Now, one other thing recently we're excited about, I would say in the last six months, two scientific discoveries have really modified our thinking in moving into more of a platform idea. And one is, I'm running out of time, so I'm gonna be really quick. This is a paper from Avery August. He's like the world's expert in ITK at Cornell University, showing that blocking ITK, either genetically or using our drug, soquelitinib, causes this, the switch from IL-17 production to Tregs or suppressor T cells.
Now, for those experts in the audience, Tregs are that's the holy grail of autoimmune disease treatment. Okay, you want Tregs. They're suppressor cells. So this led him to then show in an asthma model in mice, same thing, switching from IL-17, from TH17, which makes IL-17, to the Treg, and very effective in an asthma model in mice. So what are the opportunities in inflammatory diseases? Pretty significant. TH2 diseases, asthma, atopic dermatitis, IL-17 diseases, psoriasis, IL-5 diseases, COPD, eosinophilic granulomatous polyangiitis, et cetera, and systemic sclerosis, because TH2 is an important cell in fibrosis. We have a paper coming out at the ACR meeting in November, in a very, very sophisticated genetic model of systemic sclerosis. This drug is very active. It's a paper by Joanne Kahlenberg, who's like the world's expert in scleroderma.
Okay, so this led us to atopic dermatitis. Why atopic dermatitis? Unmet need, big market, skin. A lot of the biology pointed us in that direction, and basically, we're now enrolling. We're nearly done with this first cohort of a clinical trial that's a placebo-controlled trial, where patients with moderate to severe atopic dermatitis have to have failed one prior, get sequentially randomized into one of four cohorts. Fill up cohort one, then two, three, and then four. And we're looking at various doses of soquelitinib. They're randomized either to the active drug or placebo. The patient and the doctor are blinded. They're blinded. They're getting either a placebo. They don't know what the people who are doing the scoring and so forth don't know what they're getting.
The company is not, so we get to look at this data every month 'cause we wanna know what's happening. The endpoint of this is, in addition to safety, of course, is EASI score, the severity index of your eczema, of your atopic dermatitis. So, I can tell you already, we're seeing very interesting activity in this. We're seeing cytokine changes that are really interesting, that you would think are consistent with the mechanism of action. We're learning some new things, and we're really excited. But here's something we didn't realize. Most of the patients getting randomized on this trial have not yet failed, have not yet gotten Dupixent. Because doctors are telling us that patients don't want the injection, they want the oral medication first before they get that. And that's really influenced our thinking a lot.
So think of this as something you're gonna get before Dupixent, because patients are preferring that to getting the injections. So we expect to be presenting data on the first couple of cohorts by the end of the year on this trial. Okay, and I'll just close with some of our near-term milestones. The most important one, we started enrollment in the phase III. We'll have data from the atopic derm study by the end of the year. We're also gonna be presenting some interesting data in prostate cancer and renal cancer at some of these other meetings later this year. Thanks for your attention. Sorry, I'm over.
Thank you so much, Richard. It was a great presentation. Sorry, we've run out of time.