Good afternoon, everyone. Welcome to Jefferies Healthcare Conference, day one. Today with us, in this session is Corvus Pharmaceuticals. We have the CEO, Dr. Richard Miller. Okay, the floor is all yours. Thank you, Liang. First of all, I really want to express my gratitude to the sponsors, Jefferies Global Healthcare Conference, for inviting us again to give you an update on Corvus. Joining me today is Mr. Jeff Arcara, who's our Chief Business Officer. So what I want to do today is provide an update on the company, focus mostly in on our ITK inhibitor, soquelitinib, which is really turning out to be a technology platform, which I think cuts across many disciplines of medicine, cancer, immunology, autoimmunity, and perhaps others. So with that, let's just start with an overview. Soquelitinib is a small molecule, ITK inhibitor, orally administered. It's a covalent drug. It binds a target called ITK. I'll describe what that is in a moment. We've now validated the importance of this target in our lymphoma studies, which have shown a significant tumor regression in patients with advanced T-cell lymphoma. We are about to start a randomized registration phase III trial with soquelitinib as a monotherapy in patients with relapsed T-cell lymphoma. We are also, as just announced a couple of weeks ago, enrolling in a phase I trial in atopic dermatitis. This is a randomized, placebo-controlled trial with data that will be available probably within a few months or by the end of this year. This drug has a novel mechanism of action that speaks to its potential as an immunotherapy in cancer and also as a therapeutic agent in a variety of autoimmune and sclerotic diseases. Very strong intellectual property. We have patents issued in the major territories that run until late 2037, composition patents without any pharmaceutical extensions. We also have a variety of very, I think, strong patent applications protecting methods of treatment, monitoring, and various other effects on cells. I'm not going to spend much time on the right side of this slide. We do have an A2A antagonist that's in a phase I study now in frontline renal cell cancer, which has been enrolling very nicely. I'll give you another update on that at the end of this talk, and mupadolimab, an anti-CD73 antibody. And then finally, we have a very experienced team with individuals that have been responsible for drugs or antibodies that you all know and have been paradigm shifting in medicine, like Rituxan and ibrutinib, among others. I won't spend much time on this. You can see where we are with the ITK inhibitor, soquelitinib, about to start phase III, in phase I, in atopic dermatitis, and planning to do various other immune diseases as well. So let's talk about ITK. ITK stands for interleukin-2-inducible T-cell kinase. It is a kinase that is restricted in its tissue distribution to T cells and NK cells. It's homologous to an enzyme that my team worked on at Pharmacyclics called BTK, or now known as the drug ibrutinib. Okay, so BTK is in B cells, and when we started Corvus, we said, "Okay, let's do the same thing for T cells that we did for B cells." And so we were able to make a small molecule, selective ITK inhibitor. Now, ITK is a little bit more complicated, and we have been pioneering the science behind this target, I would say. So ITK is not only involved, as shown on the left-hand side of the slide, in the T-cell receptor pathway. That's similar to BTK in B cells. More of more interest to us was its role in the differentiation of normal helper T cells into three cell types, called TH17, TH2, and TH1. Now, we knew that several studies done in the early 2000s by very good investigators showed that if you selectively knock out the ITK gene, you block TH17 and TH2 production and the cytokines that come from those cells. You've heard of these cytokines, IL-4, IL-13, IL-5, IL-17, and many, many others. So those are blocked. Those are prevented in a genetic knockout. However, the genetic knockout of ITK still allows you to make what's called a TH-one cell. As tumor biologists, we love that because TH-one cells give rise to cytotoxic killer cells. Those are the cells responsible for killing cancer cells and eradicating virally infected cells. The reason TH-one cells are allowed to mature is because they have a redundant enzyme called RLK, also known as resting lymphocyte kinase. So our goal, our objective, based on all the experience we had with ibrutinib, was let's recreate what the genetic knockouts did. Let's make a drug that just hits ITK and spares RLK. Now, we've published on the chemical structure of this. We've published on the specificity of it. We have successfully made a drug that hits ITK over RLK with, like, 1700-fold selectivity, which is quite, quite extraordinary. So, the goal of this drug then was, could in a mature individual, would you see what you see in genetic knockouts, newborn mice? The answer to that question is yes. To prove this, or to learn more about it, we started with our good old friend, lymphomas. So, Rituxan and ibrutinib started in lymphoma and then moved into autoimmune disease, so we took the same strategy. This time, however, you have to start in T-cell lymphomas because ITK is in T-cell lymphomas, not B-cell lymphomas. T-cell lymphomas are less well understood. They are not as common as B-cell lymphomas, but they're still pretty common, 20-25% of non-Hodgkin's lymphomas. They are intractable. They are very difficult to treat. There is basically no curative therapy, and although patients will respond to frontline chemotherapy, most of those patients will relapse within less than a year. Once you have relapsed disease, the median overall survival, as shown on the right there, is about six months, with a very rapid fall in those Kaplan-Meier curves. As a matter of fact, in the NCCN guidelines for the treatment of relapsed T-cell lymphoma, the guidelines are to go on an experimental drug, even though there are a couple of drugs that have accelerated approval. I'll go into that in a moment. So we've been conducting a monotherapy, monotherapy study, looking your typical phase I study in very refractory T-cell lymphomas. We looked at 100, 200, 400, 600 milligrams BID, orally administered, and we determined that the optimum dose was 200 milligrams BID, even though we went up to 600. We used 200 for our, what will be our phase III and our expansion, which I'll describe here. Why did we pick 200? Number one, it gives you full occupancy of the target. We can measure the drug in the target, something we pioneered with ibrutinib, by the way, similar assay used. So no reason to give more because you have 100% blockade. The second reason that we picked 200 is that there's various immunological tests that show if you go way too high on the dose or the concentration, you begin to inhibit the proliferation of the good T cells, and you don't want that. So this drug is actually working by Th1 skewing, by inducing normal host T cells, normal host T cells to kill the malignant T cells. So this is the straightforward on our expansion cohort, 200 milligrams BID, our phase III eligible patient population. There were 23 patients. We reported this data in May, just a month ago. Of the 23 evaluable patients, we had 9 objective responses. That's 9 responses using Lugano criteria, very strict criteria. It has to be a 50% tumor regression, and of the 9 responders, 5 were complete responders. Complete responders mean all the tumor is gone, all detectable tumor is gone. Those are very hard to get in this disease. Usually, you see that in 5% or 10% of patients who respond. You can also see that there are many other patients on this waterfall that experience tumor regression that doesn't quite meet the criteria for PR, but nonetheless, tumor shrinking is a good thing, and, of course, there's a subset of patients that progresses. Some of these responses are quite durable. You can see on the swimmer plot on the left, we have patients who've had responses now ongoing up to 2 years. So let's compare soquelitinib in our refractory patients to belinostat and pralatrexate. Belinostat and pralatrexate are two drugs that received accelerated approval on single-arm response rate studies done about 15 years ago. The confirmatory trials were never done by the company that markets this drug, those drugs. So, by comparison, if you look at our soquelitinib data in a comparable patient population, our ORR is 39% versus 25, 29, with a doubling of the CR rate, as I mentioned, and a much longer progression-free survival, exceeding six months versus 1.6 or 3.5. Okay, some of these drugs will induce a response, but they're usually very, very short-lived. Okay, so what about safety? One of the big advantages that we have, of course, it's oral, it's very convenient, and it really has been free from any significant side effects. Belinostat, by comparison, and pralatrexate are basically both chemotherapy drugs. They cause myelosuppression, that is anemia, thrombocytopenia, neutropenia, nausea. Belinostat is an IV injection, five days a week, repeated every three weeks. Very inconvenient. Pralatrexate is a weekly IV injection, given weekly. In addition to the bone marrow suppression, is hindered by very significant mucositis, sloughing of the mucous membranes. Soquelitinib has really had no major safety issue. We don't see any evidence of hematologic suppression. We don't see any evidence of renal, liver, or any other significant side effects. So let me give you an example of what we're talking about here. Again, I want to emphasize this is monotherapy. Okay, this is a patient with relapsed refractory T-cell lymphoma. This is a bad disease. This patient already failed a few different chemotherapy regimens, as shown on the right. She had circulating tumor cells, bone marrow was packed, lymphadenopathy, splenomegaly, and a huge mass growing out of her abdomen. That's about the size of a football. And you can see within 15 days, she had a very good PR, went on to be a CR. She's still on therapy for 2 years. She's now PET-negative CR. Now, one of the reasons that we started in lymphoma, as I mentioned earlier, was that we could not only monitor the effects on this terrible refractory disease, but we can also look at the effects on normal T cells and determine whether or not there's a role here for immune therapy of autoimmune or inflammatory diseases. And really, this has paved the way for us. Similar to what we saw with Rituxan and ibrutinib, what we learned in these lymphoma patients really helped us as we expanded the opportunity. In this slide, very quickly, I won't go through all the details, but in this patient, if you look at the blood in the tumor, when you biopsy it, you find a reduction of the Th17 cells. That's the green curve up on the left there. That drops. The Th1s go up, just like we said in our little cartoon earlier. If you look over on the right, Th2 cytokine, IL-5, that's a quintessential IL-2 Th2 cytokine, that drops along with the eosinophil count. When you see that kind of drop, think asthma, think atopic diseases, think about all those other things. Instead of blocking IL-5 directly, we block the cell that produces it. Of course, if we look in the tumor, we say, see similar things. We see an increase in the CD4 and CD8 effector cells, these cells that get turned on by these Th1s to kill the tumor. Okay, here's just another patient. I show a couple of patients because they're so powerful, you don't need really to be a statistician to figure this out. This is a patient who had, again, peripheral T-cell lymphoma, NOS. That's a type of peripheral T-cell lymphoma. She had multiple sites of disease. She failed CHOP chemotherapy. This is typical. They respond and then fail right away. Then she got a bone marrow transplant. If you're young and you get, you know, into a remission, even a partial remission, you can get a bone marrow transplant, although I would say that's not widely used, but it is used sometimes. She failed that in less than a year. Then she went on monotherapy, oral soquelitinib, had a CR, lasted 25 months. Here's a patient with what's called transformed cutaneous T-cell lymphoma. Cutaneous T-cell lymphoma is really kind of a different disease. It's more indolent, but not when it transforms. When it transforms, it changes its characteristics, it changes what it looks like under the microscope, and it's bad cancer. This is a lady who had failed several other therapies, and as you can see, she's now a PR on treatment for about a year, actually more than a year now, and she has continued slow regression of circulating tumor cells. Her blood counts are now normal, and she's had a significant reduction in these tumor nodules and plaque. These are tumor, tumor plaques on her extremities and the rest of her body. So this has led to discussions with the FDA about a registration trial, which they actually requested us to do. So here is the design now that's been discussed with FDA. It's finalized. It's ready to go. The statistical plan, eligibility, everything is ready to go here. It will take relapsed PTCL. You have to have greater than failed one therapy, at least one therapy, no more than three. And we had figured out previously that if you have too many prior therapies, you're so immuno incompetent that it's hard for the drug to work. I like to say you can't get blood from a stone, so you have to have some basic immuno competence to begin with. So, there's 150 patients that will be enrolled, one-to-one randomization to soquelitinib, 200 milligrams PO BID, versus the choice from the physician of pralatrexate or belinostat. As I mentioned, those are the two drugs that received accelerated approval, not full approval, no definitive trial ever done. And as a matter of fact, the FDA is not happy about that. They held a meeting in November, just six months ago or so, where they really admonished the company for not having performed their trial. These drugs, I believe, if we're successful, will be taken off the market. Anyway, it doesn't matter that much because not many people use those drugs, because they don't work very well, as I showed you. Their median duration of response is quite short, and they have significant toxicities. So this is a trial that we're going to start in Q3, just a few months from now. It'll be open at 40 centers in the U.S., Canada, Australia, and South Korea. The crème de la crème of centers, the Dana-Farbers, the MD Andersons, the Memorials, the Stanfords, the UCSFs, the UCLAs, all the best places in the country. Okay, now, the market, there's been some, I think, bad press about this market, and let's just think about this a little bit more clearly. First, it's a bad disease, and there's no treatment. There's no treatment. The NCCN guideline, as I mentioned earlier, is like, go on an experimental trial. Well, that's great, except there aren't that many experimental trials around, and the ones that have been done haven't had the same thing, side effects, and haven't succeeded very much. So the comparator for us is an antibody conjugate called Adcetris, Seattle Genetics, which is approved to treat Hodgkin's disease and a subset of peripheral T-cell lymphomas. Only about 20% of our target population can get Adcetris. So the total sales of Adcetris last year was $1.6 billion. Now, about half of that is for T-cell lymphoma, the CD30 positive T-cell lymphoma, which is called anaplastic large cell lymphoma or ALCL. That's only, again, 20%, 15, 20, 25% tops. So I like to think that this market is right now $800 million for 20% of it, but all of these patients, when they relapse after Adcetris, or if they're not eligible for Adcetris, are eventually eligible for our drug. So I think this is easily... You can take $800 million and divide it, I'm sorry, and multiply it by 3 or 4 or 5, whatever, whatever number you want to use. It's a significant opportunity, and it's the entry point, the first step, because we have now shown, and others have confirmed, that this TH1 skewing that I described earlier works, at least in mice, in solid tumors that don't express ITK. And the mechanism is very similar to what we've shown in humans with T-cell lymphoma. That is, you get this TH1 skewing, you block TH17, TH2, skew to TH1, you generate more, cytotoxic T cells, eradicates the tumor. Because of that, we're planning to do a phase I study in relapsed renal cell cancer, together with the Kidney Cancer Research Consortium. This will start later this year, where we're going to take PD patients who failed a checkpoint inhibitor, and they'll be treated with monotherapy of soquelitinib until they progress. Once they progress, they'll have nivolumab or an anti-PD-1 added, and that's happening because there is a lot of evidence I don't have time to go into, that ITK is very important in the PD-1/PDL1 axis, and by blocking both, that would really be synergistic. So solid tumors are on the map. People ask me, "Why renal?" Yes, there are other tumors we could do, melanoma, lung cancer, gastric cancer, et cetera. You name all the PD-1 immunologically responses. We picked renal because we have a relationship with this organization. It's a tumor that we understand. We've done trials in renal before, and really, it was an expedient way to prove the concept for us. Okay, so let's get back to the strategy. Start in lymphoma, entry point, T-cell lymphoma, but it was never our intention to just stay in T-cell lymphoma. We want to expand this into solid tumors and into immune diseases. We block Th2 and Th17.... That's great! Those are the cells that are the culprit cells for psoriasis, and rheumatoid arthritis, and a bunch - asthma, and psoriasis, and atopic dermatitis, et cetera. So the strategy is based on this mechanism. soquelitinib will block Th2 and Th17 cells, and conceivably all the downstream cytokines: IL-4, 5, 13, 17, 23, 31, 33. Okay, take Dupixent, for example, blocks IL-4 and 13 by blocking the receptor. It doesn't block IL-5. Or take the IL-5 blockers, they don't block IL-4 and IL-13. Conceivably, soquelitinib will block all of those. Not only block all the known ones, but block ones that we don't know about. These are complex diseases, and to think that we know every cytokine that's involved is probably a little naive. So what are the diseases? TH2-driven diseases: asthma, atopic dermatitis, eosinophilic esophagitis. IL-17-driven diseases: psoriasis, ankylosing spondylitis. IL-5-driven diseases: fibrotic diseases, which are TH2-driven, quintessential one being scleroderma or systemic sclerosis, pulmonary fibrosis. A lot of diseases. So again, this is a platform. Now, I'm happy to report, and we presented this data at a scientific meeting a few months ago. We now have about 12 or 15 second- and third-generation ITK inhibitors that hit different parts of the molecule, have different function, functional consequences. So there's an opportunity here for a suite of products blocking different immune diseases. Okay, so with that, the first disease we're starting with is atopic dermatitis. This trial started a few weeks ago. The design is to enroll 64 patients with a moderate to severe atopic dermatitis, who failed at least one prior therapy. There are four cohorts. Patients will be randomized sequentially into each cohort, 3 to 1, where active versus placebo. We're looking at 100 milligrams BID, 200 QD, 200 BID, 400 QD. We're bracketing what we've selected for cancer. We're going lower, and we're going higher. Now, keep in mind, atopic dermatitis is not, is not, a T-cell lymphoma, where patients have a median survival of six months. This is obviously a benign disease. We have to be a little bit more careful, and we think that cancer is much harder. It's much harder to block all the cancer cells than a few, a few million TH2 cells in a lesion. So atopic dermatitis was picked because it's a known TH2-driven disease. It's easy to monitor. There's good scoring, scoring systems, and we can get biopsies and other things to monitor, you know, the activity of our drug. So the study is gonna be open at about 20 centers in the U.S., academic and non-academic centers. As I mentioned, it's enrolling. Although the patient and the doctor are blinded, and the efficacy endpoint is the EASI score, it's a well-established scoring system on an area of involvement with the disease, the company's not blinded. So we can look at the data periodically, and we intend to do that after each cohort and report on that. In addition to the clinical outcomes on the efficacy, we're also gonna be doing very comprehensive monitoring of the cytokines, all the cytokines that I've mentioned in the serum at baseline and on treatment. So this is the proof of concept. This has never been done before. We're doing in people what the genetics guys did when they knocked out ITK selectively in a mouse. We're doing it now in a mature individual with diseases, and we're seeing activity in lymphoma. We've seen activity in several animal models of immune disease. I believe that if we show proof of concept here, this is a huge breakthrough. Okay. All right, I wanna really quickly mention that, we have a trial going on with a different drug now. It's an oral A2A receptor, adenosine A2A receptor antagonist. It blocks adenosine from binding A2A. Most people have focused on that as an immune-stimulating agent. Most people have combined it with anti-PD-1s. We published a paper in 2018 that clearly showed that PD-1s are okay to combine with, it won't hurt it, but the best drug or agent to combine with A2A is anti-CTLA-4. I don't have time to go into the mechanism for that. It actually doesn't really involve T cells. It involves myeloid cells. And we also describe what's called a myeloid signature, adenosine signature. Anyway, this study now is being conducted by several centers: MD Anderson, Vanderbilt, University of Pennsylvania, Duke, I forget all the UT Southwestern, et cetera. It's frontline renal cell cancer, ipi/nivo plus our drug. But the endpoint is interesting. The endpoint is what's called deep response rate. The usual response is CR plus PRs, but PRs are 30%. The Kidney Cancer Consortium has already published in two studies that deep responses, if you use 50% of your criteria, 50%, tumor response as the criteria, that predicts very well long-term survival and PFS. So that's the endpoint here. We know from several studies they've done, that's usually 32% deep response rate. We are this protocol now, which has over 32 patients. I just talked to these guys the other, just a couple of days ago at ASCO, so there are now 32 patients. We've continued to exceed the pre-specified, protocol-defined, endpoint from an efficacy standpoint for proceeding, and that is a 50% improvement above 32%. That would be 48%. So we're exceeding that, allowing us to continue. So this is really an interesting story because, it really indicates that A2A has a role actually different than what most people were thinking initially, and we're continuing to work with this group on that. So let me summarize here in the minute remaining. soquelitinib and soquelitinib platform is a really interesting novel target. As far as I know, we have no competition in this area. It reminds me a lot of, when I was at IDEC, we made a drug called CD20 antibodies. Well, it's antibody. Nobody else was working on that. At Pharmacyclics, we made a drug called ibrutinib. Nobody else was working on that. That's great. That's really great. You want to be there. And we now are extending this into all sorts of indications, and it looks like it's active. And now this opens up a lot of opportunities, and this is Jeff's main purpose at the company. Main objective is clever partnering strategies where we can leverage all these different opportunities, whether it be with different compounds, same compound, et cetera. We recently raised cash in a deal that an equity deal that was priced at $1.73, 7% above the market on that day. It has raised $30.6 million. That alone gets us into early 2026, if no other revenue comes in. But there's a one-year warrant on those at $3.50. So if those warrants are exercised, which I expect to happen, especially when we get our atopic dermatitis trial, that would give us another $60 million or so. That would be enough to finish the trial, to finish the phase III trial. So we think we're in good shape on this. We think we have a broad platform, lots of partnering opportunities, and really working in areas where we have no competition now. And I love it because it reminds me a lot of Rituxan and ibrutinib. Now, eventually, there'll be a lot of competition, but I think that we have a very strong patent portfolio. With that, I'll take any questions if we have time. I think we might be a little over. Yes. So, Doctor, I know you mentioned that you have limited, you know, competition for soquelitinib, as ITK inhibitor. So, you know, in the atopic dermatitis, it's pretty competitive space. Yeah. Recently, we've seen, like, there's an ITK inhibitor and JAK3. So could you comment on that? Yeah. What's the key differentiation? Yeah. Yeah, I mean, atopic dermatitis, atopic dermatitis is a very competitive space, and that does scare me. But we went into this disease because it really proves the concept of ITK inhibition and blocking Th2. So this really sets the stage for others. We do have certain advantages. It's oral, it's really safe so far, it's novel, nobody else has it. And, you know, we'll have to see how efficacious it is and what the exact clinical role is, whether it's relapse patients or whatever. But this is very different than a JAK inhibitor. JAK inhibitor has much more side effects, which in this population is a problem. Keep in mind, this drug has never been tested in normal individuals. It was tested in lymphoma patients. We filed a new IND with the FDA, so our lymphoma safety was sufficient in a really sick patient population to allow us to go into relatively healthy patients with... So we feel good about the safety profile, the mechanism, the oral. You know, is it gonna work better than Dupixent? You know, I can't say that, but, it'll be different. And if it works in atopic dermatitis, you're gonna have people who want to move it into asthma and scleroderma and everything else. So again, it's, it's like T-cell lymphoma. We start there because there's nothing, right? You get it approved there, and by the way, we think that's a, you know, potentially reasonably big market for a company like, like Corvus, but then you're into solid tumors and a lot of other things. Think Rituxan, right? Rituxan started in low-grade lymphoma. People used to say, "Oh, that's a rare disease. Oh, it's lots of treatments work." You know, then it became $8 billion because it worked in so many other things. Thank you. All right. Thank you. Thanks, everyone.