Corvus Pharmaceuticals, Inc. (CRVS) Earnings Call Transcript & Summary

Good morning, everyone. Welcome to the 43rd Annual JPMorgan Healthcare Conference. My name is Grace Cho, and I'm one of the associates on the JPMorgan Healthcare Investment Banking team. Our next presenting company is Corvus Pharmaceuticals. And speaking on behalf of the company, we're pleased to have CEO and President, Dr. Richard Miller.

Thank you, Grace, and thank you, everyone, for coming to this presentation. I have a lot to cover, so I want to jump right into it. What I'd like to do today is provide an overview of Corvus Pharmaceuticals, but really focus in on our ITK program in soquelitinib, which we think is a first-in-class molecule that has broad applications in many areas of medicine such as cancer and immune diseases. So let me start with an overview of our ITK inhibitor platform and soquelitinib. As I mentioned, broad applications in oncology and immunology, our lead molecule soquelitinib is in a Phase III registration randomized trial in relapsed T-cell lymphoma, and I'll go through that with you, the rationale for that and the data from our Phase I. That same drug is also in a Phase I randomized trial, placebo-controlled in atopic dermatitis. There's very strong intellectual property protecting the molecule, composition of matter patents have issued in the United States. Forward-looking statement. Oh, I have to -- sorry. Composition of matter patents have issued in the U.S. and run until late 2037, and that doesn't include pharmaceutical extensions. The markets that are addressable by this drug are potentially very large. I don't need to go through them. Obviously, cancer and immune diseases are big markets. Let me just show an overview of the pipeline of the company. We're all in on ITK and soquelitinib, as you can see from this slide. I mentioned the Phase III T-cell lymphoma trial. There's a solid tumor study that's going to start with this molecule in a month or so, atopic dermatitis Phase I randomized trial going on, and I'm going to present updated data on that a little bit later in my talk. We're about to start in collaboration with the NIAID, a study in a rare disease called ALPS, ALPS Autoimmune Lymphoproliferative Syndrome, which is basically a very, very bad autoimmune disease and a couple of other opportunities that we may start later this year in other immune diseases. So my team and I have always been interested in this intersection between lymphoma an immune diseases. And that's because when you think about it, lymphomas are religious cancers of the immune system and what you learn in lymphoma can have applications in autoimmune disease, because there are really just two sides of the same coin. So this turned out to be true for rituximab, a drug that I worked on an antibody that I worked on, which, of course, got approved very quickly for lymphomas, but then went on to get approval for autoimmune diseases like rheumatoid arthritis and psoriasis and things like that. Ibrutinib, another drug my team worked on, BTK inhibitor started in lymphoma, learned a lot what it does to normal lymphocytes and then, of course, expand it into now what's being used in many different autoimmune diseases. And so I think the same thing will be true with soquelitinib. But here, we focus on T cells, T cell lymphoma and T cell diseases of the immune system. So very quickly on the mechanism of action, this is precision medicine at the quintessential example of precision medicine. So ITK, the target of our drug, stands for interleukin-2-inducible T cell kinase. It's involved in T cell receptor signaling as shown on this cartoon. But more important to the team at Corvus at the inception of the company was the involvement of this target in the differentiation of normal helper T cells into what are called Th1 cells, Th2 cells and Th17 cells. This is now in textbooks of immunology. It's Th1 and Th2 cells were first identified, I think, 30 or 40 years ago. But what was very important to the Corvus team was genetic studies done in the early 2000s showed that if you precisely knocked out the ITK gene, nothing else, you inhibited Th17 and Th2 cells and the resulting cytokines that come from those cells. Those are well known to you in a lot of diseases like IL-4 and 5 and IL-17 and IL-13, et cetera, many others. But you still permit the differentiation of what are called Th1 cells. And those were important to us because as cancer docs, we said, well, Th1 is good. Those are the cells that provide help to reject cancer and to reject or fight off viral infected cells. So we wanted a drug that could do that. No one has ever done that. People say, well, ITK inhibitors have been made before. No, but they're not specific because they also hit this RLK enzyme. RLK is an enzyme in the Th1 cell stands for resting lymphocyte kinase, which has a redundant function and allows the Th1 cell to form even when you block ITK. So the objective was to make a drug that blocks ITK, but does not block RLK. And that had never been done before. Now the story gets a little bit more interesting in just the past several months because now a few different laboratories have shown that this ITK is involved in multiple parallel signaling sequences in a lot of crucial T cells, including the Treg cell and the Th17 cell. And long story short, if you block ITK, you get a skewing, you get a shift from the inflammatory, pro-inflammatory Th17 cell to the Treg cell. Now why is that important? Because that's the possible holy grail of autoimmune therapy. Could you induce a lasting remittive effect on an autoimmune disease by inducing these suppressor cells. So we were able to make a drug shown here, published last month in cancer -- in drug discovery. And I won't go through all the details, the specificity, the binding association constant, the chemical structures, et cetera, are published in that paper, a very comprehensive paper with a lot of data in it. But one point I do want to make is that, and we knew this, we have a target, ITK that's very restricted in its tissue distribution, T cells and NK cells. We have a drug that's very specific for that target. And we have a drug that's eliminated pretty quickly from the body like in a day. So those three things are safety because the opportunity for off-target cross-reactivity is really minimized because limited tissue expression, specificity and rapid clearance. So the first disease using our strategy that we focused on were relapsed T-cell lymphomas. ITK is in T cell lymphomas. T cell lymphoma is a bad disease. I won't spend a lot of time on it here. But basically, there's really no treatments for it that work. And once you relapse from T cell lymphoma and pretty much everybody does, you have a 6-month survival. That survival curve, there is very, very ugly survival curve. And so we, using our strategy, start in T cell lymphoma, get data quickly, potentially advance it through clinical development and learn about what it does to the immune system. And very quickly, we looked at using monotherapy, just the drug, which is given orally. We went to doses as high as 600 milligrams twice a day. We saw no toxicity, no DLT, no MTD. We saw -- we were able to measure occupancy, that is the drug binding to the target. And we recognized that 200 milligrams, 1/3 of the highest dose we ever went to was safe had responses and completely occupied the receptor. So we didn't have to go any higher. And we talked to FDA about that as well. So we treated 23 patients in an expanded cohort with monotherapy, very refractory patients. And we had 9 out of 23 responses by Lugano criteria. That's a very high response rate in this disease. But the most notable thing about that is that of those 9, 6 were complete responses. Complete responses in relapsed T-cell lymphomas are extremely rare, very hard to get that. Not only were they complete responses, but some of these complete responses lasted a year, 2 years, et cetera. So those results were very good. We took those results to FDA. And this is the result of those discussions. We're now in a Phase III registration trial. The eligibility is, 1 -- you have to have failed 1 to 3 prior therapies, no more than 3. 150 patients. This disease is so bad only takes 150 patients. They're randomized equally, 75 in each arm to soquelitinib, 200 milligrams twice a day versus the standard of care agents. Now the standard of care agents are 2 drugs, belinostat and pralatrexate, which are basically chemotherapy drugs, one's an HDAC inhibitor, one is a folate antagonist. Those drugs have the usual side effects of chemotherapy. Cytopenias, myelosuppression, et cetera, immunosuppression. They have response rates, maybe 25%, very short-lived, very rare that you get a CR and the PFS is for those 2 drugs, progression-free survivals are about 1 or 2 months to 3 months. In our studies, we had 39%, 40% response rate, mostly CRs. PFS greater than 6 months. So let's look at these responses a little carefully and then I want to really try to emphasize how they pertain to the immune disease story. So this is kind of a typical patient on our lymphoma study. Peripheral T cell lymphoma. This is the most common type of T cell lymphoma. Football size mass in the skin of this patient also has circulating tumor cells and lymphadenopathy, et cetera, is on our drug monotherapy and this large mass and circulating cells go away by day 15. This patient went on to a CR, took the drug for 2 years. We stopped at 2 years while she was in complete remission. Now what's interesting is the other things we can learn from this, the leverage that we have. So we can interrogate the blood and tumor biopsies and the skin. And we can ask the question, what's the drug doing to the normal lymphocytes obviously making the tumor go away. And we can see, and I'll just go through this very quickly, a reduction in the Th17 cells, as shown on the top left there. Th17 cells remember, require ITK to differentiate, so you don't get those. We can see on the upper right, you can see a reduction in IL-5. IL-5 is a Th2 cytokine. Hard to measure Th2 in the blood, so you can measure the surrogate, IL-5 and other cytokines. And along with this drop in the IL-5, which is a reflection of blockade of Th2, you see a reduction of eosinophils from 17,000 down to below 1,000. 17,000 is very high eosinophil count. Just to put that in perspective, you've got bad asthma of your 700. So these are awesome changes. And you see similar changes in the tumor, we can measure Th1 cells going up, et cetera. So as we're doing these studies, we say, well, there might be an opportunity here in immune disease for mechanistic reasons and for what we learn -- from what we're learning in the clinic. So here's a patient with what's called cutaneous T cell lymphoma. By definition, this is a T cell lymphoma that originates in the skin. It's a Th2 lymphocyte. Oftentimes, people think and physicians think it's atopic dermatitis. They're misdiagnosed sometimes, and they get treated for atopic dermatitis except this disease doesn't go away. It gets worse and worse and worse and eventually kills you. So we see responses in this disease. So this, along with laboratory work, that we were accumulating told us that, okay, now there's an opportunity, and now we have the scientific strength to go into the clinic in autoimmune disease. So the rationale here is pretty straightforward. We have a drug that blocks as shown here, Th17 and Th2. But not just blocking those cytokines, it's not stoichiometry. This is you're blocking a functional, a function of these cells as opposed to, let's say, the list on the right there, agents that you know about DUPIXENT and SKYRIZI and all these other things you see on television every night. That's more or less blocking stoichiometrically either the cytokine or the receptor for that cytokine. So this is a very novel concept because we're blocking the cells that are producing this and other functional attributes of these cells that, frankly, are not that well understood yet. So what's the opportunity here? In addition to our work in T cell lymphoma, there's fast opportunities in immune diseases, Th2-driven diseases like atopic dermatitis, asthma, IL-17 driven disease, psoriasis, IL-5 driven diseases like allergic diseases, and fibrotic diseases, which are Th2, primarily Th2 driven, scleroderma, pulmonary fibrosis, other things like that. Okay. So this led us to a Phase I randomized trial in atopic dermatitis. Why atopic dermatitis? I get that question all the time. Why didn't you do psoriasis? Atopic dermatitis made a lot of sense scientifically. It's a Th2 disease. We see good responses in the skin of patients with T cell lymphoma. The science and the clinical information that we had from our lymphoma really pointed us in this direction, but there are other opportunities as well. So we are conducting now a Phase I trial in patients with moderate to severe atopic dermatitis. The plan is to enroll 64 patients. These patients have failed at least one prior topical or systemic therapy. There are 4 cohorts in the study. They are sequentially enrolled. Fill up cohort 1, then you go to cohort 2. Now I have to give my team a lot of credit. In less than 1 year, we went from a cancer clinical trial, Phase III trial, took all the safety, human safety data, clinical information, refile that with dermatology division, we had sufficient safety information, animal information, et cetera, started a clinical trial and have data that I'll share with you today. So that's really quite an accomplishment for less than 1 year. So the cohorts enrolled 16 subjects each at a 3:1 ratio of active to placebo, 12 active, 4 placebo. And the trial is blinded, double-blinded. Patient and the doctor do not know what they're taking. The pills are indistinguishable. The company is not blinded. It's a Phase I study. We can look at the data whenever we want. We thought that was important because we wanted to maybe amend the protocol or do things as we learned information. So the treatment, and this is important, 28 days. That's relatively short. 28-day treatment and then we follow the patients off of therapy for another 30 days, okay. The endpoints are safety. Remember, this is a dermatology division. Now I have to be a little bit cautious because this has not been tested in a relatively in a benign disease like this. And the efficacy end points are the usual things, EASI Score, IGA scores, et cetera. Now the different cohorts are designed to test a couple of different hypothesis with respect to dose. We know a lot about dosing from our lymphoma study. It's been over 100 patients with lymphoma. So the cohorts are 100 milligrams BID, and then we go to 200 once a day, same total dose but given at one time. So you get a higher peak concentration. Then we go to 200 BID. That's the lymphoma dose. And then 400 QD. So the reason for testing those different doses -- sorry, was that we know that this is a covalent drug and really what's important with a covalent drug since once it binds it irreversibly sticks to the target. And we have information and others do that the Cmax, the maximum concentration is more important than the steady state. So we saw that with ibrutinib. We saw that even early in our lymphoma studies. So we wanted to test what's more important in this disease, the Cmax are having a bigger -- a steady state. So that's the reason for those 2 dose levels. The other thing to point out is that 100 milligrams is not a very low dose. That's a pretty good dose. We learned that from our lymphoma studies. That will give you 50% to 80% occupancy of the target. Not 100, 200, 400, give you 100% occupancy, but we don't know that you need to have 100% occupancy. In fact, probably you don't. Okay. So now these are the results from cohort 1 and cohort 2 with respect to patient characteristics. Cohort 1, of course, I reported on -- we reported on back in December. That was 16 patients. Now we've added another 16. So we have 24 with soquelitinib, 8 placebos. Now we've had a very small number of placebos by design because we have this 3:1 ratio. We wanted to get data on the active therapy. And really, a couple of things to remark here. This is a pretty standard patient characteristics for these days. But just a couple of things to point out. We have a high proportion of African Americans. I mentioned that back in December. The patient characteristics in Cohort 1 and Cohort 2 are basically the same. They're really not any different. That's why I combine them. The African Americans, I'd point that out because they have worse disease. They are more refractory to treatment. So it makes the treatment a little more difficult. In fact, a lot of the studies now are trying to enroll more African Americans for many reasons. The mean baseline EASI score, 19.9%, 17.8%, a little bit better in the placebo, works against this. But those are pretty standard for these days. Now EASI scores have come down in the past decade. Everybody knows it because there is greater access to treatments, more drugs out there, more awareness, who knows. But it is coming down. And this is a real-world experience now. Now prior therapies, the thing to point out here is none of the patients on the active, the soquelitinib arm, none were on concomitant topical corticosteroids. I think they were at least 3 or 4 weeks since they had their last dose of corticosteroids. One in the placebo did take a concomitant corticosteroids. None of the patients on this study so far have had any breakthrough medication. So during the time on our study, they're not getting any other medications. This is data that we showed last month, but just to walk through it and then talk about the Cohort 2. So again, 4 weeks of treatment with a pill that, as I'll show you in a moment, it's pretty safe. The placebo mean percent reduction was 27%. Pretty good, pretty standard. I mean, typical for a lot of studies. The active was 55.9%, about a 29-point difference. Pretty good, a 30-point difference is pretty good, especially with 4-week treatment and especially with the dose that's not yet been optimized. Now look at 8 weeks. The data changes a little bit. The placebo, we had some placebos who actually got a little worse. So the mean percent easy change was 19, and our actives continue to get better, going to 69.1. That's a 50-point difference. So that's pretty good. Now let's look at the EASI 50s. That EASI 50 means 50% improvement in your EASI score, 2 out of 4 placebos, 50%. More in the active, of course, but look at EASI 75, 90 and IGA 0/1, none of the placebos. So this is why in 2016, when DUPIXENT was approved and this is published by the FDA and has been used ever since 2016 for every approved drug. They don't care about EASI 50. They don't care about mean percent reduction. What they care about is EASI-75 and IGA 0/1, they're not EASI 90s as well because those are enough of a signal above the noise to be meaningful, okay. You shouldn't get credit for something that a placebo does. So they said, okay, we -- the endpoints that you must use in your clinical trial, same thing is true in Europe, EASI-75, IGA 0/1, now you can use both endpoints, 1 endpoint co-primary, whatever you want to do, but those are the endpoints, because you have a high background in this disease because it waxes and wanes. Okay. So this is the updated data now from our studies, Cohort 1 and Cohort 2. We don't have 28-day follow-up yet on all the patients in Cohort 2. This is as of January 5 cutoff. We have 7 actives and 3 placebos from cohort 2 that have been through the 28 days. The rest of them are at different stages, of course. So first of all, let's start with the placebo 0. No placebo so far. And our study has achieved EASI 75 or IGA 0/1. Cohort 1, around 25%. Cohort 2, 29% to 57%, looks a little bit better. And by the way, the mean EASI reduction is a little lower in the Cohort 2. I'm not showing that data. And then, of course, if you combine them, cohorts 1 and 2 together on the far right, 19 subjects, 26% and 37%. This is very good data. 28 days of treatment, not 16 weeks, 28 days. As a matter of fact, if you compare this data to 16 weeks of therapy, SOLO-1, 2 which granted is a 900 patient trial, registration trial for DUPIXENT, what you'll see is usually placebos will be about 10% to 15%. So I would expect some placebos to reach this target, but we haven't seen it yet. And you might see anywhere from 35% to 52% of EASI 75s or IGA 0/1, but this is a very good result, especially 28 days. Now of course, we're going to continue to follow these patients. We're going to look and see whether the remit of effect continues, if there's continued improvement, all that stuff is being collected as we speak. Okay. Now what about safety? Really, the drug has been very, very safe. We have experience now in over 100 patients with lymphoma. We have over 9,000 patient days of treatment. We've had lymphoma patients on this drug for 2 years, as I said. In the soquelitinib arm, we had one new AE. It was a headache at day 57. That means you're off the drug for a month and somebody reported a grade 1 headache. So that's really not too significant. And we had 1 AE in the placebo, which was a grade 1 URI, upper respiratory infection. So safety continues to look really good. Okay. So sort of just to kind of wrap up and summarize. So we have a drug, oral, safe, new mechanism of action, potential broad number of indications. And in vitro studies, animal studies and some of the human studies indicate that we block a lot of these Th2 and Th17 cytokines. And we have these additional cellular functions. On what are called innate lymphoid cells, which I didn't go into here and also T regulatory cells or suppressor cells. None of the other agents have that. In fact, the efficacy I showed you is beginning to look a little bit like JAK inhibitor type efficacy in terms of EASI scores. Of course, there, they're treating for months. We're treating for 28 days. Of course, we're going to look at longer duration of therapy in the future. But anyway, we really do think that we're restoring immune balance or changing the function or resetting sort of the immune system here with this treatment. And then finally, to summarize, oral drug, new mechanism, very specific drug, safety in over 100 patients with lymphoma and atopic dermatitis. Efficacy, preliminary evidence of efficacy in cohort 1 and 2. Cytokine changes I reported on last month. We do see changes in serum cytokines that seem to correlate or relate to response. I think it's too early to be definitive on that. Responses appear to be durable. We're seeing that in the cohort 2 as well. Potential for broad number of indications. And of course, dose optimization is going to continue. We know we need to look at other doses. In a couple of weeks, we'll be starting Cohort 3, 200 BID, which is, we think, is our best dose. That's our lymphoma dose. And of course, at some point, lengthening the duration of therapy. So looking ahead, the key milestones around soquelitinib over the next year or so. The Cohort 2 data I've presented this week. A full data set midyear, end of second quarter 2025. The ALPS study should start. We should get answers from ALPS very quickly. because the end points there are changes in lymph node size, easy to do and changes in cytopenia. So all you need to do is follow their hematocrit and their white count, and their platelet count because they have autoimmune thrombocytopenia and neutropenia and anemia. Solid tumor study soon. And then we are now thinking about the second indication for autoimmune disease, which we think we can fire up by the end of the year. So with that, I think we'll take questions. And I appreciate your attention.

Thank you for the presentation. We'll open it up to the Q&A now. And for the Q&A portion, we will also be joined by Chief Business Officer, Jeff Arcara. I can get started here. How do you see this oral drug being positioned in the management of patients with atopic dermatitis? Would it be before or after injectables?

Let me take that. I've been getting that question a lot. It's interesting when we started the study, we were agnostic to that. We allowed you to be pre-DUPI post-DUPI or systemic therapy. I actually thought that we would be getting mostly the DUPI failures in post-DUPI. But what we're finding is quite the opposite. Almost all the doctors and the patients prefer to go on an experimental oral agent as opposed to taking an injection. And I ask myself is the fear of needles. They just -- most patients just don't want to step up to that degree of seriousness. They just want to try the oral agent, see if it works and then perhaps use the injectable later. So I think that this could actually be a frontline therapy. Now I also get the question all the time, what will it work in DUPI failures? Well, all I can say is I don't know because we don't have any data on that yet. But I see no reason why it wouldn't. It's a totally different mechanism of action. And in cancer, my field, when you treat a patient with cancer with drugs, and they stop responding. You don't go getting the same drugs with the same mechanism. You go give him different drugs with different mechanism because they're resistant or their pathophysiology has changed. So I think that we're going to have a broad opportunity here. But I think the real world experience so far is that -- I mean, we had a study open at 17 centers. And I can tell you, most of these people prefer to use it before they go to an injectable.

You were able to share 7 patient data from the Cohort 2. How are the other 5 patients trending specifically on the EASI 75 versus the 57% on the 7?

Okay. So the other patients are at different periods of time, so some are shorter and some are longer. I think that looking at the curves and the changes in EASI scores, they're trending as good or maybe slightly better than the cohort 1. The study wasn't designed to have statistical power to say, hey, cohort 2 is better than cohort 1 or vice versa. We're really, really looking for -- this has never been done before. This has never been -- this is ITK specific drug has never been tested in an immune disease to my knowledge. And so the fact that we're seeing efficacy at 100, maybe slightly better at 200, we'll see if that trend continues. But obviously, at some point here soon, we're going to have to do a Phase II trial and we're going to examine probably a couple of doses, probably increase the duration of therapy, and we'll probably get better results if we do that. I look at this drug a little bit different. I mean, of course, DUPIXENT and these other drugs, you have to take forever because when you stop them it comes back. Most patients stop the drug because they feel better and they don't want to take it anymore. I see this drug as maybe controlling your disease. I mean, I'd like to see it as curing it, but I'm not that naive yet. I see this drug as controlling the disease and then maybe stop, maybe comes back at some point in the future, you take it again because it's pretty safe and easy to do. And -- so we'll learn about all that. So there's a lot of things here, expanding the -- not just exploring the dosing and schedule but also a lot of other diseases. I think it's going to be really interesting to look at this in asthma and fibrotic diseases and other inflammatory diseases. This ALPS study, the rationale for that by the way, was we tested it in what's called an MRL mouse. That's -- some people think a model for lupus and it cures these mice. And these mice have this autoimmune disease with a mutation that is exactly what these people with ALPS have. The mouse and the human actually, it's a genetic disease. So children are born with it, and by age 2, they have lymphadenopathy and anemia and all kinds of blood count problems, proteinuria because of skin disease. And they have the same mutation in the mouse does. And the drug works so well in mouse. We said, oh my god, we got to test this in patients. And now we're starting with 18 year olds. We can't go right into children. But eventually, we will. Any other questions?

For the expression of ITK in lymphoma patients versus the atopic derm [indiscernible], 2 more T cells obviously the lymphoma and the density on the cell. So is there -- is the measure in cancer in terms [indiscernible] does that apply...

No, I don't think so because the interesting thing is, first of all, ITK is inside the cell. It's not on the surface. And even in lymphoma, and this is why we're going into solid tumors, the way it's working is Th1 skewing is inducing the normal T cells to fight the cancer cell. So the effect that we're seeing is on normal T cells, and it's a really good point you're raising because mutation is not an issue here. It's not like cancer, ibrutinib in B-cell lymphoma, where the target can mutate and then the tumor won't respond anymore. These are normal T cells we're working on and those cells are not mutating. So I wouldn't expect resistance.