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 of Investigative Dermatology meeting a couple of weeks ago. But 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 Jeffreys folks for inviting us to the healthcare conference. So let's get going. I know it's late in the afternoon, and I'll try to be as exciting as I can. So first of all, socolitinib is a first-in-class immune modulator, which we believe has broad opportunities in immune diseases. So 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 socolitinib is it's now enrolling patients in a phase 2 randomized, blinded, placebo-controlled trial in atopic dermatitis. It's also enrolling a phase 3 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, many diseases in different areas. And I really believe that socolitinib has the potential to be used across many, many areas of medicine, dermatology, oncology, rheumatology, pulmonary medicine, etc. 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 Soqualitinib. So 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, an eight lymphoid cell. The drug, Socolitinib, is very specific for ITK. So when you have a very limited tissue distribution and a very selective, a very specific drug, that predicts or anticipates safety because the possibility of off-target side effects, reactions, is more limited. Specificity and selectivity is a key. That's what you strive for when you try to discover a drug. Okay, now the mechanism of socolitinib 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. Now, you've probably heard about some of these cells in 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, hydradenitis, superativa, and other diseases as well. Now 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. But 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. So the ideal drug, and what Corvus was successfully able to do, is to make a drug that just blocks ITK and spares RLK. Now the story gets more interesting, in the last few years now 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. And when you block ITK, genetically or with socolitinib, you shift it to Treg. Now what's a Treg? A Treg is the break, suppresses inflammation, suppresses immunity. For decades, people have been looking for ways to boost Tregs to fight autoimmunity because you want to suppress autoimmunity. Okay, so now let's sort of put this together. Why are we excited about socolitinib? 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, Dupixin, Renvoke, two that I'm sure you've all heard of. So they hit isolated cytokines, and that's very good, but inflammation is very complicated. It has many, many cell types, many, many different types of cytokines, so 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, because 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. So you have, again, this point about selectivity, but broad in its potential. Now, 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 T-Rex. It also means that you might work in diseases that are resistant to these drugs, because it's working by a different mechanism. It doesn't care if you had Dupixin because we're going to block those cytokines plus others. So here's the status of the socolitinib development pipeline. As I mentioned, starting at the top there, phase three, registration, randomized trial, socolitinib versus chemotherapy, ongoing, interim data late this year, interim futility analysis late this year, final data, second half of 2027. Now, for TH2 diseases, atopic dermatitis, phase one data we just reported, I'll review that with you here today, atopic dermatitis, phase two randomized blinded trial, enrolling data, third quarter, 2027, asthma study we plan to start later this year, that's a TH2 disease. cells, very important in asthma, hydroadenitis superotiva, a TH17 disease. We want to expand the opportunity by going into TH17 disease. That study is starting later this year as well. And then 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 socolitinib is very broad. of its mechanism we can think about th2 driven diseases those you're all familiar with asthma atopic dermatitis eosinophilic esophagitis etc etc targets of many many large drugs drugs now il-17 diseases psoriasis depixens great and ad not so great in the psoriasis doesn't really work we have a drug maybe could work on both those diseases or others that are 17 driven like psoriatic arthritis, ankylosing spondylitis, HS, as I mentioned. IL-5 are allergic diseases because we impact IL-5 and eosinophils. And then 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. So the opportunity here is very, very large pipeline in a product. So these markets are large. I think you're all aware of the, 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 percent 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. But yet the oral component, the number of drugs that will be orally administered to address this market, still only a small percentage, 10%. So there's obviously a large opportunity for growth with an oral agent that addresses these diseases. Okay, so we've conducted a phase one 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, aha, it looks like it could have an effect in TH2, normal TH2 lymphocytes, TH17 lymphocytes. Let's start looking at animal models and confirm this. We do that and we confirm this. We say, aha, interesting. We find atopic dermatitis models we work. We say, hey, T-cell lymphoma, that frequently involves the skin, too, and under a microscope looks just like atopic dermatitis, so we should go into atopic dermatitis. And 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, hematological illnesses, are just two sides of the same coin. They're basically both caused by disturbances of lymphocytes, B-cells in the case of ritux and 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. So we've conducted a trial, which is really quickly because it's already been presented, phase one 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, three to one randomization. Looking at different doses, 100 milligrams BID, 200 once a day, same total dose, 200 twice a day. And then we looked at that data. We said, oh wow, this is really interesting. It looks like it's working. So then we said, okay, we're gonna treat, now 24 patients, one-to-one randomization. We're gonna go with what looks like the most efficacious dose for now, because we really wanna prove the concept, prove that the efficacy, safety looked great, and we added another 24 subjects shown there as cohort four. And what we're monitoring, of course, is safety and the usual efficacy parameters of atopic dermatitis, easy scores, IGA, et cetera. Now, cohort four, we did another thing. we doubled the duration of therapy. So, cohorts one to three were only 28 days with 30-day follow-up. Cohort four, we doubled the duration. And here's what we find. It's pretty simple. For cohorts one, two, and three, where we increase the doses, 28 days of treatment, you have an increasing response, measured by EZ75 and IgA0 and one. Goes from 25 to 33 to 50%. Placebo background was zero. Now, people are like, why is placebo zero? Well, we only treated patients for 28 days, so that's a short time. Placebos are bouncing around, so there's less of a chance to hit UC75. And we actually enroll sicker patients. And I will go over that in another slide or two. We had a sicker population, which also reduces your placebo effect. Now, when we go to eight weeks, shown on the right, new group of patients. Eight weeks, get a higher response. higher is EZ75, IgA0, et cetera. Okay, now 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 one to three, four weeks, the last cohort was eight weeks. You can see a pretty substantial difference between placebo and cohorts one through four. No cherry picking, all the patients, okay? Actually statistically significant, although we didn't power it for that. Again, this was a phase one exploratory study. Now, on the right, it gets interesting. Those are, we enrolled, we allowed you to have prior systemic therapy before you came on our study. Now, you have a washout period. You weren't on it when you came in, but you were allowed to either have failed it, been unresponsive, or at least have received it. Most studies exclude those kinds of patients. And when you look at that data, that's 35% of our patients on the right, the response rate to Sokol isn't about the same. Didn't matter if you had prior biologic. Remember, I told you it shouldn't matter mechanistically, so we expected that. Look at the placebo is worse. So 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. Now, 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 then have a washout period, get randomized to our trial, get so-called itinib or placebo. Here's what happened. And you can see their prior therapies, dupe, dupixin, methotrexate, JAK inhibitors, RENVOC, et cetera. these guys didn't respond to that I mean didn't respond at all okay they come on our study the percent easy change easy 91 easy 96 easy 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 so this is your perfect controlled experiment so to say so 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. So what about durability? I talked about these Tregs. These Tregs are really important. They're antigen-specific cells. So 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. So this looks at cohorts 1 to 3 on the left, right at the end of treatment, week 4. You can see the blue is EC75 at the end of treatment. The hatched bars are the IGA01s, and you can see 30 days, 60 days, 90 days. There's no deterioration of the response, and if anything, it got a little better. So there are no treatment there. They're still blinded. The doctor and patient are still blinded. They don't know what you've got. Then we go to cohort four, where we only did 30-day follow-up. Same story. Now, the eight weeks of treatment, the blue bar is higher, as we showed before. The IgA zeros and ones are higher. And 30 days later, it's unchanged. There's no diminution in the response. Okay, now let's compare that to what you would expect. And 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. to because it's pretty clear. So if you look on the left, what I'm showing here is data from Savinco phase 2b trial. The bottom two curves are the approved doses, 100 and 200 milligrams. You can see that the easy curves come down. They plateaued 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. Now, 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. And 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, so you don't see that with placebo. This is true of all the JAK inhibitors. Controls the disease, rapid rebound. It's true of Dupixin. Dupixin, as shown on the right, there's that percent improvement on the y-axis. They take, in this study, this was their phase three trial. They'd take patients who respond, do PICS and 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 of it. You get approval for what you did at, this was 16 weeks of therapy. We'll do 12 or 16 eventually. But then they randomized, because they were testing a few things. They randomized to different maintenance programs or to placebo, no treatment. And 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. So there's some lag in there. So the rebound happens right away. So every drug, every drug, pretty much every drug is associated with rebound, and it occurs in four weeks or less. Okay, four weeks or less. So 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 twos and phase threes. But 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 and you're going, 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. And 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. But 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. But that asterisk up there is really important. Those are what are called key 67 Th2 cells. They're proliferating. Those are the ones that are activated and responding to whatever the inciting agent is. So, again, the specificity here is really critical. The middle and right panel showed the effects in cohort 3 and 4 on IL-4, 5, 13, and TARC. Well, IL-4 and 5 and 13, we expect that to come down, and they do. They do come down. But 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. And by the way, their disease was still getting better and they were stable and so forth. So that effect, again, of the Tregs and the persistent effect beyond the life of the drug in the body is really of interest. Now TARC also dropped in the drug-free period because patients were getting better. Now TARC is not a target of IATK inhibitor, so 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, now, 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, and yet it's one of the most effective things. So 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. So now is the, I think, the crucial part of the story. So here, we are able to measure Tregs in the blood using some very sophisticated flow cytometry techniques. And basically, this is looking at placebo and so-called itinib-treated patients. On the top is cohort three and four, well, on top left is 28 days on the drug for cohort three, 28 days on the drug cohort four. On the bottom is 30 days after you've stopped the drug. About 30 days after you've stopped the drug in cohort three is 30 plus 28 is 58 days. And in cohort four, that would be 86 days after we started the drug. But in both cases, you see a very substantial increase in these Treg cells, both at the time you've finished your treatment, the last day of treatment, and then 30 days after you've stopped the treatment. These Tregs are persistent, is the point. So 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. Okay, now 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, STAT-6, and those sort of things. All important. Well, one of the things that became glaring to us in the data was we were having this upregulation of something called SOX3. Now, that's not one you're very familiar with, but it's well known in immunology. SOX3 stands for suppressor of cytokine signaling. It is a negative feedback to the JAK-STAT pathway. Too much inflammation, SOX3 goes up, shuts down JAK-STAT signaling. well-established. So we see that treatment with socolitinib increases SOX3, increases it. SOX3 down-regulates, inhibits JAK1 signaling and STAT6 signaling. And on the right is just more granularity on that, on those findings. You see SOX3 going up in TH2 and TH17s. TH1s, it goes up a little as well. Now, interestingly, there is an effect on STAT6. Pretty good effect, 10 to the minus 15 B value between what it was at day zero placebo, sorry, at the pre-treatment baseline and at the end of treatment, there's a reduction in STAT6. But 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 where 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. So we have a pretty good effect on JAK-STAT signaling. Is that a surprise? Not at all. You look at the patient, you know, I have this inflammation. So none of this is surprising or inconsistent. Okay, now let's talk about safety. Okay, there are no safety signals from socolitinib at this point in time. And we have this over hundreds of patients now with T-cell lymphoma who are sick. I mean, 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 socolitinib, which is why it's a registration phase three 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 one to three, that's four weeks of treatment. Cohort four separately, that's eight weeks of treatment, so twice as long. And basically, there's really no, the incidence of grade one, grade two 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. and really there's nothing that stands out here there's no effects no adverse effects on liver function tests hematologic parameters kidney parameters etc so so far this drug has a very very clean safety profile okay now what are we going to do so going forward phase 2 trial enrolling patients now open pretty straightforward same eligibility moderate to severe AD we're allowing up to 40% of patients who have had a prior systemic therapy. We have to cap it, otherwise we'll have 100% because patients, 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 milligrams once a day, 200 twice a day, which is the dose we're using for lymphoma, 400 milligrams once a day, placebo. 12 weeks of therapy, that's longer than the 8 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. And the usual endpoints here, easy 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 so-called for China only to Angel Pharmaceuticals. We really kind of run and monitor the trials in conjunction with them. They have about 35 employees. So their trial is meant to complement ours. we can use their data for regulatory files and vice versa. So 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 milligrams 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 in placebo, placebo is blinded. Then 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. Then it rolls into the cohort two, which is another 24 patients with higher doses, 200 milligrams BID and 400 milligrams once a day. So 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. But 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 like Dupixin. Okay, so they have a greater component of Th17. That's good for us, because we hit, we block Th17. So that's another thing that we're expecting out of this. Now, when they finish that part of it, it automatically rolls into another 60 to 90 patients, dose to be determined based on the first part of the study, you know, sort of a phase two trial, basically. Again, placebo-controlled. Okay, so what's the development pathway for us? Development pathway for us is very straightforward. It's just like everybody else. We did a phase one trial just like everybody else. We're doing a phase two, as I just described, Placebo, active, 12 weeks of therapy, easy scores, IGA. You don't need to follow, you're going to follow patients, but that's not part of the ultimate development strategy for approval. Phase three 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 easy scores and IGAs, that's your approval path. Now, other things like maintenance and all that other stuff, that comes later, post-marketing. And I'm sure there will be a lot of interest to do that. Oops. Sorry. Okay. So I want to say one quick word about our Phase III trial in lymphoma. This trial is enrolling. We do expect it's a 150-patient trial, one-to-one randomization, chemotherapy versus socolitinib, PFS endpoint. We do allow crossover because patients want the drug, they want a crossover, but they have to progress first. The interim analysis, futility analysis by the end of this year. So the upcoming events for us are start our HS trial, second half of 26, start our asthma trial in the second half of 26, data from the ANGEL trial in late 2026. So that's an important event for us. Okay, let me close by saying the key messages for us is that our phase one AD study is as good as any efficacy data you're gonna see out there, in my opinion. The safety so far, although early, is very, very good. We don't see infection, we don't see any evidence that that will be a complication. complication. So right now we think we have a very, 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. And 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.
Richard Miller
CEO