Corvus Pharmaceuticals, Inc. Aktie

Okay. We'll continue with the next session. Thank you for joining us. I'm Paul Choi, and I cover the SMID-cap biotech sector here at the firm. It's my pleasure to have Corvus Pharmaceuticals here for our next session. My immediate left here is Jeff, who is the CBO of Corvus. Maybe what we'll do is let Jeff kick it off with some high-level comments on sort of what are the company's priorities for the remainder of 2026 and going into 2027, and then we'll go into questions after that.

Sure, sure. Yes. So maybe I can give a little bit of an overview of the company and talk about some of our competencies and priorities. So Corvus is a clinical stage company. We're developing novel immune therapies for the treatment of cancer and immune diseases, soquelitinib is our lead program. It's in a Phase III registrational trial for peripheral T-cell lymphoma, which is a really tough cancer as well as we're in a Phase II trial for moderate to severe atopic dermatitis and that's called the SIERRA1 trial. And both of those trials are enrolling as we speak.

Based on soquelitinib's target and mechanism of action, we think it's got a pipeline and a product opportunity. So in the second half of this year, we'll be starting an asthma study, a Phase II asthma study as well as a proof-of-concept study in HS. Just of note, we have really good composition of matter protection on soquelitinib. So we have protection through November of '37, and that doesn't include any pharmaceutical extensions, which could be an additional 5 years. And then ITK represents a platform technology for us. We have a number of next-generation and backup compounds in development.

So in terms of like our focus, I think maybe 3 things I can think of is we're really good at developing novel science, ITK, which stands for interleukin-2-inducible T cell kinase. It's involved in T cell receptor signaling and differentiation. We're really good at chemistry, so we can make very targeted and selective drugs, and that's important not only for efficacy, but also for safety. And we've gotten a very experienced management team that's done this before developing drugs like ibrutinib and Rituxan and bringing those to market. Does that make sense?

Yes, it does. So if we think about it this way, an investor might look at your company and say, wait, you're developing the same drug for a blood cancer and also in the dermatology space, how does that work potentially? And what is the rationale, I guess, to go from a Phase III program in a blood cancer into I&I? And more specifically, atopic derm. Can you walk us through what was sort of the background behind that?

Sure. So rationale for AD. So first of all, we follow the science. So essentially, how soquelitinib works is that we block Th2 and Th17 in their respective cytokines. So you think about we block Th2, we block IL-4 and 13, just like DUPIXENT, which, of course, is approved for atopic dermatitis. In addition, we block Th17. So therefore, we block IL-17 which is also involved in atopic dermatitis as well as other immune diseases. So the biology and the target made sense. In addition, for atopic dermatitis, any new therapy safety is absolutely required because you're actually treating 18-year-olds with eczema.

One thing that's really interesting about ITK is ITK has very limited tissue distribution. It is only found on NK cells and T cells. And we have a drug that's targeted and selective for ITK. So therefore, we think we'll have limited off-target effects. So I think that's important. And then finally, I think in terms of the current standard of care, we have an oral product, right? And so I think that's a big differentiation. Obviously, you've got DUPIXENT. You've got lebri and nemo, all injectables. So I think we have more patient preferred and with an oral product. Now of course, there is Rinvoq, right, which is an oral tablet, but it is -- does have the label, has the safety warning in the label as well as it requires monitoring. So we're hoping to improve on that as well. So that's the rationale for AD.

You touched on this a little bit, but with respect to the AD landscape, very dense, very competitive, which I think is a fair assessment. But can you maybe talk about how soquelitinib differs versus some of the other AD0 drugs that are either commercially approved or in clinical development. Then also on the oral side, there are some other oral programs that are out there on the JAK side and STAT6 programs. So maybe can you just walk us through the landscape there?

Sure. I mean, it is a crowded landscape, but it's going to be a huge market, right? It's a big market now, and it's projected to go to $30 billion and maybe even $50 billion by 2030 or '32. So significant opportunity. Now there's a lot of drugs in development that are subcu. And when you look at the pipeline for novel drugs, novel oral drugs, it's actually fairly limited. I mean, you've got us an ITK inhibitor, of course, there's STAT6 that you brought up. There's also IRAK-4 that's in development. I think Sanofi has a program there, but that actually there's been some negative data in AD in the past.

So I would say novel oral not as competitive, but still competitive. So the question is, how would we differentiate from other orals I think, first, the target that we just talked about. So we could be potentially first-in-class selective ITK inhibitor coming to market. I mentioned the limited tissue distribution. One thing we -- they tend to be expressed in a broader set of cells and tissues. So you can find them in the skin, in the lungs, in the GI tract, where again, we have this limited tissue distribution. So we think clinically that should support a good safety profile.

I think the other thing that is unique about our mechanism of action is that we not only block cytokines, but we also believe that we're modulating for rebalancing the immune system. And what do I mean by that? So not only we block Th17 and the respective cytokines style 17, but we've actually shown to be able to shift or switch Th17 to become active T reg cells. So in some ways, we're kind of taking our foot off the gas and also strengthening the brakes at the same time. And I think that leads to a third point of potential differentiation based on working more upstream and this mechanism of action, we actually think we could work in a broader set of patients. And I think there's an example of that in our January data when we released, we had about -- I think it was 35% of our patients were on a prior systemic therapy. And actually, we worked very good in those patients and even in patients that had failed prior systemic therapy.

So I think we might be able to work on a broader set of AD patients and in a broader set of illnesses and indications as well. That's a number of characteristics of how we could differentiate.

Since you brought it up, maybe you can recap for us your recent data. What sort of -- you talked a little bit about the population, roughly 1/3 of them were patients who have previously failed a systemic therapy. But can you maybe just compare and contrast how your recent data looks compared to the current standard of care and some of the existing therapies?

Yes. So we're -- we think we have pretty compelling clinical data. When you look at EASI-75 and IGA 0/1, we're somewhere between a biologic and JAK level of efficacy. So EASI-75 is actually comparable to a JAK placebo adjusted and IGA 0/1 comparable to a biologic. So we're pretty excited about what we've seen so far, and we hope that we can replicate that in our Phase II trial, which is ongoing the SIERRA1 trial.

Great. Another aspect of the data that you presented was patient follow-up through 90 days off treatment. Can you maybe recapitulate that for us? This is something that's kind of not typically followed in AD development. So can you maybe tell us what that data looks like and then just how do physicians and KOLs you've spoken with since you've released said data view this result?

Yes. Yes. So it is interesting data to see this kind of follow-up post stopping the drug. Maybe what I would say first is that our plan is to bring soquelitinib to market as quickly as possible. And we'll do that through standard continuous dosing first. And so just like what J&J just did with ICOTYDE, right, which was just approved for psoriasis. That's basically one pill once a day, and that's simple. So that's our plan. So we're going to follow the typical clinical development and regulatory path that's already been paid for us to bring the market -- soquelitinib market quickly in AD.

Now to your point, in the SIERRA1 trial, we are going to follow patients longer term. So it will be a SIERRA1 trial is a 12-week study for efficacy for treatment and then we'll have a 90-day follow-up off drug. So we'll see what that looks like. If we continue to see that durable effect, we'll continue to study it in future trials and likely it will be part of our lifecycle management strategy. Does that make sense?

Yes. And then maybe physician feedback on the response or duration of response off treatment. What have doctors said about this?

Yes. I mean they're encouraged. I think just in general, physicians are looking for more durable treatment and treatments with less treatment burden. But I will say efficacy is still #1 as it is for any drug. So I think they're excited to see the EASI-75 response and the IgA-0 response, which is what we've shown just with continuous daily dosing, which is why we'll pursue that for the initial indication.

Based on your data to date, as you think about soquelitinib in AD, is there a particular group or aspect or subgroup of the population or part of the population that you think makes most sense for the target and the mechanism of action here?

Yes. Yes. It's a good question because we work more upstream because we blocked Th2 and Th17 we brought -- we block a broader set of cytokines. We actually think we're going to work on a broader set of patients. And I think that actually aligns us up for actually like a first-line treatment, actually. And again, I mentioned that we've shown that we can work in patients that have actually failed a prior systemic therapy I think, obviously, in terms of making decisions about positioning and segmentation, it's really going to be driven by the target product profile. So we'll see what that looks like after the Phase II and that can inform some of these commercial strategy decisions.

You did present a 90-day off-treatment data for cohort 3, but you decided in your most recent update not to present that for code for Cohort 4, excuse me, can you walk us through the rationale behind that? And just was that protocol-driven or just was there anything else behind it?

Yes. I think 2 things. I think first of all Cohort 4 was meant to look at 2 months of efficacy dosing. And that was the purpose of Cohort 4. It actually wasn't to follow for off-treatment durability. So just as a reminder, cohorts 1 through 3, we're only 4 weeks of treatment. And when you looked at those curves, you actually saw the kinetics of those curves still pointing down. So we saw that, boy, if we kept treating, we might get a deeper responses. So that was the purpose of Cohort 4 to see what a depth of response that we could get and we absolutely did see that. And that was important because we needed to design the Phase II trial and start the Phase III trial, and we want to move forward as quickly as possible. So that was the purpose of Cohort 4.

In addition, we were already enrolling cohort 4 before we actually saw the 90-day Cohort 3 data. So we would have actually had to amend the protocol. We would have had to go back to the RV sites it didn't really make sense from a standpoint, from a time and money standpoint. So we decided it was just best to move forward. The purpose of that trial was a proof-of-concept trial to support the moving into Phase II. And we felt like we accomplished that and we wanted to move quickly. Does that make sense?

Yes, it does. You guys are working on prosecuting development of soquelitinib here in the U.S., but you've also engaged with a partner for ex U.S. markets, specifically Angel in China. Can you maybe remind us of what is their clinical development plan, how does that trial look like compared to yours? And then when might we potentially see some data from your partner in China?

Sure. So Angel is our partner in China. They have the right to soquelitinib and are developing it there. Corvus owns 46% of Angel, as you know. And they are running a very similar program to your point. So they're running a Phase Ib program that will lead into a Phase IIb trial in atopic dermatitis. So they have 2 cohorts. Cohort 1 is low dose, and that's a QD versus BID. And then Cohort 2 is a higher dose QD versus BID. And then based on the results of those 2 cohorts, that will inform the dosing for the Phase II portion.

So by the end of the year, we should see Cohort 1, which -- that will give us 12 weeks of dosing, which we don't have yet. So that will be interesting as well as we'll be able to see what the effect is at the low dose for QD. So that's what we'll have at the end of the year from Angel.

One of the big obsessions of Wall Street biotech investors is the difference in translatability of drugs in development in different geographic populations. Can you maybe just briefly recap for us how the treatment paradigm in China might differ and also any other sort of clinical differences between the Chinese population in the U.S. or Western population?

Yes, it's a good question, right? And I think that's one of the reasons we're starting with a lower dose cohort because we're studying in a Chinese population, so we want to be careful, right, and study it thoroughly. One thing that's interesting that Richard talked about is actually there was a study that showed that Chinese patients actually have higher incidence of IL-17, Th17 and IL-17 for atopic dermatitis. So with the fact that we blocked both Th2 and Th17, it will be interesting to see what the effect is in this Asian population. So -- but otherwise, all else is going to be the same in terms of enrollment criteria, EASI score, end points, EASI score -- primary endpoint is EASI score reduction, secondary points will be IGA 0/1, and EASI-75.

Great. Maybe turning back to your program and your Phase II SIERRA1 study. Can you walk us through the trial design and just how are you thinking about prosecuting that and what time lines might be both to enroll and potentially time lines to data?

Sure. So we're enrolling SIERRA1 now. It's a global study. we'll have about 70-plus sites in North America and Europe. It's a 200-patient study, and this is very similar to all the other programs like lebri, nemo, did a similar size study. So 200 patients. We have 4 dosing arms. So we have a placebo and then we have a low dose, again, QD, and then we have the 2 high doses, QID versus BID. And so it's a 12-week study, as I mentioned, and then we have the 90-day follow-up. And so we will look to read out that data in Q3 of 2027.

Okay. And just in terms of end points, any differences versus what you've done in your Phase II or should investors also look towards EASI-75 and IGA 0/1?

Yes, most part, it's the same endpoints. EASI-75, IGA 0/1, PNRS pretty much the same.

Okay. I want to turn back to a moment towards efficacy and thinking about sort of treatment options for patients who have been on prior therapies, and you present efficacy there. Can you remind us in SIERRA too, what portion of patients might be on -- have been on prior therapies? And do you -- maybe starting there?

Yes. Yes. So as I mentioned, in the Phase I trial, we had about 35% of patients on prior systemic therapies. In the SIERRA1 trial, the Phase II trial that's going on right now, we can have up to 40% patients on a prior systemic therapy. So we'll continue to look at that. And I think it's interesting. Of course, from a positioning standpoint and interest in the drug being an oral drug, most physicians as well ourselves, we see this as a frontline drug as a first-line drug prior to the injectable. But it's interesting to see this effect in prior systemic treated patients. So it gives you some optionality as well for future life cycle decisions. So again, we'll be able to see that data and look at that. We can have no more than 40% in the SIERRA1 trial. So we don't really know what percentage of patients that we'll see.

I want to double-click on that a little more because as you're running a trial with both frontline and treatment-experienced patients, this could have downstream implications for how to your point to how the drug is used whether as you envision it as a frontline trial or as a drug for refractory patients. Does that also think about your pivotal trial development down the road, would you similarly pursue a mixed population?

I don't know. We'll have to see from the Phase II trial. Again, being a novel oral safe product, I think most physicians and ourselves see this as a frontline drug in front of the injectables. But I will say you have to also look out 5 to 10 years, right? And if in 5 or 7 years, you have a biosimilar DUPIXENT and it's priced at $4,000 a year, you may have payers requiring you to step through some of these therapies. So if you do know you work in these, say, refractory patients or priorly treated patients, that's a benefit. But right now, I think if we're novel oral safe, we probably see it more positioned as a front line. Does that make sense?

Yes, it does. Maybe sticking on CR1 and your Phase II program. Can you maybe lay out how you're thinking about the differences between your dosing arm, specifically your 200 mg BID versus your 400 mg QD dosing? Are you expecting daylight between the [indiscernible] to be similar than different? Just how do you think [indiscernible]

[indiscernible] versus BID. Maybe a couple of things. So first, it's important to note that soquelitinib is a covalent drug, right? So once we attach to the target, we stay on the target. And this target, of course, is the ITK protein. The ITK protein has a half-life of 12 hours in terms of its turnover. So we'll stay on the target longer than the drug will stay in the plasma.

As a reminder, Cohort 1 and Cohort 2 were the low doses, but it was QD versus BID. And both those doses were effective. They separated from placebo. But remember, it was only a 4-week study. So with a 12-week study, we hope to see that the Q QD dose will be as effective as a treatment because our target is to have a QD dose. And that doesn't include any sort of formulation options you have as well. I mean, actually, Rinvoq is actually a long-acting -- but our target is to have a QD drug. So we hope to see that in the SERA01 trial, actually and in the Angel trial as well.

Yes. I want to turn for a moment to your oncology program because sometimes it gets overlooked. You're actually in Phase III already and relatively far along here. So can you remind us, first, what is the status of that study in PTCL?

Sure. So we're in a registrational Phase III trial for PTCL. That trial is enrolling 150 patients in about 40 centers and enrollment is on track. The primary endpoint for that is PFS, and that's versus current standard of care, which is belinostat or palatrexate, at least in the United States. And unfortunately, they're not very effective drugs. So there's a very, very high unmet need in PTC -- so our plan for that is that, by the end of the year, we're looking to have a futility analysis. So it's just essentially a go/no-go look at the data, and that should be out by the end of the year. And actually, by the time we enroll for the futility analysis or have enough events for the futility analysis, we probably have actually enrolled the entire study. So most likely, we'll just finish up the study and then submit the package because our goal is to have a full approval for the drug where the current therapies have -- they're under accelerated approval only.

Can you just remind me if the futility analysis will be done on a blinded or unblinded basis? And if not, is there any statistical penalty from doing this?

Like alpha yes, no alpha penalty.

No alpha penalty. Okay. You referenced currently available treatment options and including belinostat. And can you maybe just refresh us on what have these available options shown in PTCL in terms of the standard of care? And how do you think about, based on your prior data, what soquelitinib might do in terms of improving on efficacy here?

Yes, yes. So unfortunately, they don't work very well. These drugs were approved a long time ago. In fact, I think the FDA has got their eye on these drugs because they haven't done the pivotal drugs or pivotal studies. You see anywhere from, unfortunately, like 1.5 to 3 months PFS for these drugs. So most patients are going to come off these drugs due to toxicity or to just lack of efficacy. And in our PTCL trial, we actually have a crossover. So if patients fail on either belinostat or palatrexate, they can cross over to soquelitinib. So unfortunately, just still a high unmet need in terms of current standard of care.

Just on that crossover arm part, can you just maybe walk us through how that might down the road affect a potential OS analysis? How do you think about that? And just sort of the implications there?

Yes. So the primary endpoint is PFS. And I think we're looking at just under 5 months PFS, basically doubling what is currently there. And we've already had discussions with the FDA. We have an approvable for one trial. But look, I mean, our OS, I think if I remember right at the ASH meeting is I think we're almost 28 months. So very different. So we are seeing an effective -- an effect on these patients. And again, to keep it, it's a novel oral drug, which is also a big advantage for the [indiscernible]

You mentioned this briefly earlier, but just on the registrational path within PTCL, how do you think about this? Is there a way to fast track it for either a regular approval? Or are you thinking about more of an accelerated approval with a final approval post your data or full approval downstream?

Okay. Yes. So we have fast track status today for soquelitinib. There's a high unmet need that we just talked about. So assuming the data is supportive, we will and can talk to the FDA about regulatory path, so potentially an accelerated approval or breakthrough therapy designation.

Great. I want to give the audience a moment to ask any questions if they have any, happy to pass around a mic, if necessary. Just raise your hands, and we'll be happy to get a mic to you. But in the meantime, can you just sort of remind us of how prevalent PTCL is and how you think about the commercial opportunity there?

Sure. So prevalence is about 70,000 patients globally. In the U.S., it's about 10,000 patient prevalence, EU, 15,000 prevalence and the rest, the balance is Asia. It's more prevalent in Asia because it's actually -- a lot of it is driven by EBV and the virus. So in the U.S., the incidence is around 3,300. So -- and unfortunately, most patients get chemotherapy, but unfortunately, most patients fail. So they're going to pass down to the refractory patient population, which is where we're studying it right now. So look, I think with a high unmet need and a small orphan in terms of the size of the market, it's a significant opportunity for us. It's probably underlooked.

Okay. Can you remind us, you have fast track status for soquelitinib here in PTCL. But if you are successful here with your clinical trial and theoretically get an approval, can you walk us through what the exclusivity implications might be from getting an approval here? You talked earlier about composition matter going to 2037 with possibility of extensions there, but just maybe sort of what are the exclusivity implications from getting it maybe the first new drug approved for PT cell in a long time.

ure. Yes, absolutely. And so we also have orphan designation. So obviously, assuming a successful approval in the U.S., it gets you 7 years of exclusivity and in Europe, it gets you 10 years of exclusivity as well. So that would give us some additional protections in addition to the composition of matter patents that we have.

Maybe turning back to ITK biology. I think you and I and Richard have talked about its applications potentially in other non -- other therapeutic categories outside of AD and also PTCL. Can you maybe talk about where you're investigating soquelitinib currently beyond those 2 lead indications and where you think ITK biology might be applicable?

Yes. Yes. So as I mentioned, we'll -- in the second half of the year, we'll start a Phase II trial in asthma as well as a proof-of-concept trial in HS. So like I mentioned, at the front end, we follow the science. So asthma is a Th2-driven disease, very much similar as to AD. In fact, the overlap, I think, is about 25% of adults and up to 40% of children have concomitant disease. So we're following the science with asthma. Still unmet need for oral tablets in general for most I&I diseases. It's the same in asthma. Also, there's some efficacy opportunity as well. About 25% of patients in asthma don't respond to current therapies. And you're talking about a very large market there, 60 million patients in the G7, 10 million patients moderate to severe.

So it makes a lot of sense from the biology and from the market opportunity and our profile to look at asthma. HS is really interesting, right? That's primarily a Th17-driven disease, and we've shown clinically that we can actually really impact and lower TH or IL-17. BIMZELX was recently approved. That's been a very successful drug, and that blocks IL-17A and F. So we think the biology makes sense there, at least for soquelitinib. That's about 1.2 million patients in the G7, about 700,000 patients that are moderate to severe.

And actually, I was just looking at Evaluate Pharma, and they actually now have that projected to be an $8 billion opportunity starting out of $500 million. So I think it's going to grow. So I think both opportunities are significant for soquelitinib.

Maybe just sticking with the asthma advancing soquelitinib. Can you talk about which in terms of -- you talked about moderate and severe patients. But is there a particular group within that, whether it's EoE-driven disease, other areas that make most sense for you to investigate first?

Yes. Obviously, EoE makes sense. In addition to blocking IL-4 and 13, we block IL-5, right? And so obviously, you've got Fasenra, you've got Nical, are very successful drugs. They're a couple of billion dollars each, and they're effective in asthma. It's an interesting point you bring up. Obviously, the larger portion of the market is T2 disease. So that's 70% of the market. But the subset of non-T2, there's a subset that's actually driven by IL-17. And because we block both Th2 and Th17, we could potentially work in the non-T2, obviously, the drugs like TEZSPIRE that are approved there. So we're still designing the Phase II protocol for asthma, but that's something we're considering is could we actually maybe include at least a segment of non-T2 as well that could expand the market opportunity for us.

Great. And then on the HS side, typically, patients go through HUMIRA, which is approved for that. But clinical development in HS has been a bit of a land -- mind field, excuse me, for clinical stage drugs. Can you maybe talk to what your learnings are from competitor programs that have had some stumbles recently as you think about developing a clinical program in HS?

Yes. I mean we're -- so we're talking to our KOLs right now. So we are very cognizant of what you're bringing up. And I think that's why we're doing a proof-of-concept study in HS versus saying a Phase II trial in asthma. So I think we want to be -- have a definitive answer in terms of the study design, but we also want to make sure we're managing our resources. And there's a number of things that we're looking at in terms of endpoints and how you manage placebos and how you're measuring some of these endpoints are still being discussed. And so it's an evolving field. But you do have a pathway now with BIMZELX. There's other drugs in development. So we are looking at a number of protocols to make sure we kind of optimize the HS protocol, and we're working with some of the KOLs now to finalize.

Maybe looking a little bit into the future after asthma and HS, you've talked about historically about a range of diseases that might also be subject to ITK biology. Maybe what would sort of be the focus areas for investors down the road as we think about development?

Yes. I think in our slide deck, we have a slide that kind of talks about the diseases by biology. So Th2, Th17, fibrotic diseases, IL-5. So I think it's interesting is IBD. I think IBD is very interesting, right? And we have a number of really good animal models that show that we're pretty -- that we can impact the biology of IBD. So I think that's something we'll consider and look at. And again, I think, obviously, we've got soquelitinib that's in the clinic. So we may do a number of these proof-of-concept studies with soquelitinib. But then the question might be, would it make sense maybe to switch to a next-generation ITK inhibitor just to maximize the opportunity, right, in terms of patents and Inflation Reduction Act and that sort of thing.

Can you remind us what your cash position is currently and what your cash runway does -- takes you to in terms of prosecuting your current programs in the clinic and just how you think about the needs for your pivotal trial program, pivotal stage programs?

Sure. So in January, we raised $200 million. Our balance sheet as of March 31 is $237 million. And what that buys us is that we have money to complete the Phase III PTCL study, the Phase II atopic dermatitis study, the SIERRA1 as well as the asthma and the HS study. And that gives us a runway into mid-2028.

Okay. Great. There are no questions from the audience. I think we'll end it there. My thanks to Jeff and Corvus for joining us today.

Welcome, everybody. My name is Richard Miller. I'm the CEO of Corvus Pharmaceuticals, and we're delighted to be conducting this webinar and in-person meeting at the Society of Investigative Dermatology Meeting, where Corvus and its collaborators have 2 papers, 2 posters and the pleasure of having 2 of our speakers, 2 of our presenters speak here today with you. So this is a very exciting time for Corvus. I think you'll see both from some of my introductory remarks and from the speakers that we have here today that Corvus really does have a very special compound that's going to have applications in many, many areas of medicine. And so let me start with our forward-looking statements, and introduce today's speakers in addition to myself.

I'm very happy to have Dr. Albert Chiou here. He's a Clinical Professor of Dermatology and the Director of Clinical Research in the Department of Dermatology at Stanford University Medical Center, along with Albert, Dr. Kavita Sarin. Kavita is a Professor of Dermatology and an expert in precision medicine and genetics also in the Department of Dermatology and also in the Cancer Institute at Stanford.

Now I picked these 2 speakers for a reason. Yes, they're very smart. Yes, they have -- they're very photogenic. But more importantly, they complement each other. That is clinical research together with the science and elucidation of mechanisms, which is going to hold for us the promise of new applications and better ways to use our drugs and understand them better. So these 2 speakers really complement each other and really add to the scientific prowess of Corvus. They make us smarter, and they set new standards, higher standards for us every day.

Let me start with the agenda for today. I will make some introductory remarks. And then we'll have Dr. Albert Chiou talk about the treatment landscape for atopic dermatitis as well as review the clinical data from our Phase I trial. Now interestingly, we heard this morning from Kavita on the biomarkers. That was probably would be better to have the clinical first, but the schedule of the meeting, we can't control. So Dr. Sarin went first, but she gave a brilliant talk and is going to go through that again for us. So after Dr. Chiou, Dr. Sarin will go through the immunologic and biomarker data. And I use the word immunologic deliberately. It's more than a biomarker. It's fundamental biology. We have learned new things about this disease and about the immune system.

Then I'm going to follow Dr. Sarin's talk with some key takeaways, if I'm able to summarize their beautiful work as well as talk about our pipeline. And then I hope we have time for Q&A, both from the people in the room and those in the back, you guys can move up here. We have more seats up in the front. So we'll have Q&A from people in the room here as well as on the webcast. And I know we have a very large audience on the webcast.

Okay. So with that, just some details on the papers that we're talking about. On the left, Dr. Sarin's talk was this morning. A really beautiful talk. I hope that you can look at her slides and go through it, but she is going to cover most of that today. There's a poster session this afternoon with her data, and she'll be there and able to answer questions in more details if you have any. And then on Saturday morning, Dr. Chiou is going to deliver his paper on the Phase I clinical results. I think that's going to be a very important paper. The poster on that paper will be tomorrow afternoon as well. So a lot of details that they're not able to cover in the usual 10-minute talk.

Okay. So let me start with sort of get everyone grounded. Soquelitinib is a first-in-class drug. Why is it a first-in-class? Because other people have talked about ITK, a target, and I'll get into that more in a moment. But really, nobody was able to make a drug that just hits ITK. And that's because it's hard to do. ITK has several closely related enzymes called the TEC family kinases. And some of those just have 1 or 2 amino acid differences in their structure and their ATP binding site. And I'll tell you in a bit why we were absolutely fastidious about the specificity.

So we have a novel mechanism of action, first-in-class drug with, we believe, now broad opportunities because it can control so many important functions in the key immune cell called the T cell. So the mechanism of action is dependent on the high degree of selectivity for ITK. And this enables it to block many different pathways, also to reprogram T cells so that you can have a lasting effect beyond the drug. Kind of like when you vaccinate somebody, they're vaccinated, the drug is gone, but you're immune for a while. So this is sort of the same thing. The immune system has memory. It's programmable. Thank God for that because otherwise, we'd have to take medicine every day.

Oral administration, we're studying this drug mainly BID dosing. We believe eventually it's a QD administration. It's now in a Phase III trial in a very bad disease called peripheral T-cell lymphoma. It's a registration randomized trial in peripheral T-cell lymphoma. As well, we're now enrolling our Phase II trial, randomized double-blind study, Phase II in atopic dermatitis, similar to the patients that you're going to hear about in a few minutes from Dr. Chiou. We plan to enroll -- we plan to start studies in other diseases, hidradenitis suppurativa later this year and asthma. And that's just the beginning because we think that this really is a pipeline in a product, and I know that's a cliche, but this really could be that.

I had the privilege of working on an antibody called Rituxan. That was a pipeline -- a product in a pipeline, too, because it could do all different kinds of lymphomas, you could treat various autoimmune diseases. So I look at this in a similar way. The opportunity is vast, pulmonology, gastroenterology, dermatology, oncology, rheumatology, just to name a few. Strong IP. We have issued patents, composition of matter patents. It's issued in all the major territories. You can look up the patents. Those protect us in those territories through to 2042. And we have a bunch of patent applications covering things like methods of use, monitoring Th2, Th1, Tregs, et cetera, all kinds of other permutations of that, working their way through the USPTO.

Management team. So we've done this before. My colleagues and I have done this before. It's called Rituxan, it's called ibrutinib and a couple of others, BRAF inhibitors. So we know how to take drugs or biologics that have big opportunities and get it done. And we're all driven by science, medicine, good clinical research and development. That's what we pride ourselves on.

Okay. Now let's talk a little bit about the mechanism, because I think we can make some really important points here. So ITK stands for interleukin-2-inducible T-cell kinase. It's been around a long time, as I mentioned, and it's known to be crucial in many T cell functions, T cell receptor signaling, T cell differentiation, apoptosis, many, many T cell migration. It's important in many, many areas. And we know that it's fundamental in the differentiation of a naive CD4 cell into what are known as Th17 cells, Th2 cells and Th1 cells. So those are the 3 main types of helper T cells. The Th1 cell, that's important, so, fights cancer, fights infection. Th2 cell, important in protecting also against certain infections and tissue homeostasis, regeneration, same thing for Th17.

Now Th17 and Th2 cells are the cells we're going to focus a lot on today because they're involved -- they're heavily involved in inflammatory diseases. So it was shown by Pam Schwartzberg and Leslie Berg 25, 30 years ago that if you knock out ITK gene in a mouse, just ITK, what happens, as shown on the right here, is that you can't make Th17, you can't make Th2 because they're dependent on ITK. And then consequently, you can't make those cytokines. What are those cytokines? IL-4, 5, 9, 13, 31, GM-CSF, TNF alpha. When you think neutrophils in some of these diseases coming from there, GM-CSF. But interestingly, when those workers made that knockout mouse, they still were able to produce Th1. Why was that? Well, the Th1 cell has a redundant enzyme known as RLK. Sometimes in the old literature, it's TXK. You may see that terminology sometimes.

Okay. So the genetic studies showed that if you knock out ITK, you skew to Th1, you lose Th2, Th17. Now interestingly, I know there's a lot of companies out there that are saying, I got ITK inhibitor too. Most of them hit RLK. The genetic studies show if you hit RLK and ITK together, you get T cell dysfunction. You're severely immunocompromised. And of course, we don't want to do that in autoimmunity. So what we did at Corvus is say, we want to do this. So our strategy, the inventive step, the aha moment, every great company has an aha moment was, "hey, we got to make it specific for ITK and not for RLK." And we weren't really that smart, even though we were saying aha, we're not that smart. We just went to the library and read a lot. That's helpful.

So anyway, now the important thing to tell you about interleukin-2-inducible T cell kinase is that it's not all over the body. It's just in T cells and NK cells and ILC2s. We don't have time to talk about ILC2s today, but they're really important in immunology and in autoimmune diseases, asthma, atopic dermatitis, other diseases. But the specificity of the drug for a target that is only in T cells and NK cells. So that's really, really very important. So when we hear about mechanism, you're going to hear a lot of stuff about mechanism from Dr. Chiou and Dr. Sarin. Remember, it's limited to those tissues to T cells and T cells can orchestrate all these different kinds of immune effects.

I told you memory was part of the immune system. There's a second important component, diversity. It can do a lot of things. Because one day, you're getting a virus, the next day you're getting a bacteria, the next day you're getting the fungus. You don't know what -- I mean, we're getting assaulted every minute. Trust me on that. So the strategy, make an ITK-specific drug, and we were able to do that, okay? And we've published that, all right? We have an oral ITK-specific drug. It is a covalent drug, by the way. That's one of the ways we confer specificity. I wouldn't go into the details of that. But this morning, there was a question about covalency. Well, yes, it's covalent, but the protein turns over in 12 hours. So the drug is out of your body very quickly. The half-life of this drug in the body is in the plasma rather is 2, 3 hours. Okay? So there's no lasting effect of the drug once you stop it, pretty much gone.

In the mouse where we can give radiolabeled compound, we know 99.99% is gone in 24 hours. Anyway, so this is the mechanism of action. So if we can make a drug that can block ITK and spare RLK, we may inhibit Th2 and Th17 and spare Th1. That's a good thing, okay? Now each of these cells has characteristic transcription factors. So we can elucidate them. We can measure them. We can look at them in the body in the blood and so forth. GATA3, ROR gamma T, T-BET, you'll hear about another one pretty soon called FOXp3. In fact, you're going to hear about it right now. So the story got much, much stronger in the last few years.

Now there is no question. No question whatsoever. There was just another paper last week that came out from a group in New York that Th17 and Tregs. Tregs are suppressor T cells. They're the brakes on the immune response. Anytime you react to microbe or whatever, you make an inflammatory response to something's got to shut it down when the microbe goes away. Those are the Tregs, among other things. So ITK turns out to control the differentiation of Th17 and Tregs. And when you block ITK, and this was done with -- by Avery August using our drug. It was also done by him genetically, you stop Th17 and you skew towards the Treg. There's no question about that anymore. We've seen that in every experiment we do in the lab. 5 or 6 different labs have shown that. And we now see it in our patients in atopic dermatitis.

Okay. So where does this leave us? Well, we have a drug very specific for a target that's only in your T cells, which are -- is not all over the place. It's very restricted. And yet we have the ability to block various cytokines, the Th2 cytokines, 4, 5, 13, et cetera, Th17 cytokines like IL-17 and 21 and GM-CSF and others. And we can increase Tregs. I'm not going to go into the ILC2 story here, but that's an emerging, very important part of the story. Now comparing that to some of the approved agents, I mean, which you already know, those are stoichiometric. If I give an anti-IL-13, I'll block IL-13 for sure, but I won't block the other things. And I'm not really changing the function of the immune system. I'm blocking a ligand.

Now JAK inhibitors, of course, they do -- they can modify T cell responses. But many of these targets of the current drugs suffer from the fact that many, many tissues express the target, notably, the hematopoietic system and the immune system. So if we look at some of the stats or some of these other receptors or proteins, signaling proteins. They're not just in T cells. They're in T cells, B cells, myeloid cells, erythroid cells, et cetera, et cetera, et cetera. I can't name them all. I don't remember them all, but they're throughout the system. And that gets a little scary if you want to treat people for long term, if you wanted to do that with agents that are perturbing fundamental processes in the body.

Okay. So that's the foundation here. The foundation for taking soquelitinib into the clinic in immune diseases. We were already in the clinic in T-cell lymphoma. Now the reason why T-cell lymphoma is attractive is because those are Th2 cells. They frequently involve the skin, and they're really going crazy. They have no respect for the patient. They grow and grow and grow. We think we can inhibit them in a large number of patients, and that's a Phase III trial that's going on now. But along the way, as we began to put pieces of the puzzle together and as we started to do more experiments in the lab and preclinical models in animals and so forth, we began to realize that, "hey, autoimmunity and inflammatory diseases would be great." And that led us to atopic dermatitis, Th2 disease involves the skin, many of the same cytokines involved, and you can see the disease very easily. Plus, I was friendly with Albert and Kavita. No, not really. I am friendly with them, but that wasn't the reason.

Anyway, so with that, it is my great pleasure now to turn the podium over to Dr. Albert Chiou. And I think you're going to find his talk extremely exciting.

Great. My pleasure to speak here, and I actually really love this format because I get a little more time than at the actual symposium talk to double-click on the details here. So like Richard mentioned, my name is Albert Chiou. I'm a medical dermatologist over at Stanford. I serve as our Department Director for Clinical Research, and I've been involved in clinical trials for atopic dermatitis, including some of the early dupilumab trials, the IL-13 inhibitors, a number of the JAK inhibitor trials and then now soquelitinib. So I also take care of a large number of patients with moderate to severe atopic dermatitis who are on systemics, including a busy practice where we see a lot of the folks referred in from the community who have failed first and second-line therapies. So this is a topic near and dear to my heart.

And maybe I'll just start first with a reflection. Atopic dermatitis is not -- it's not a lethal disease, but it's a highly, highly morbid disease. It is really tough on our patients. So this is a combination of factors. One is that especially in our adult patients with moderate to severe disease, for most of them, this is going to be a chronic lifelong issue. They deal with very unpredictable flares. And that in itself is very, very hard on people psychologically. And then you just have this daily bother from itch and frequent complications like skin infection. So it really hits a lot of aspects of patients' quality of life, their health.

And what's really interesting about this patient population is there's a lot of varied patient preference on what is the ideal treatment for them. Even in my most severe patients, what I find is that we're oftentimes balancing these discussions of efficacy, but also what each individual is willing to accept in terms of side effects. There's also a lot of variation in what they'd accept in terms of treatment duration and what happens if they miss a dose or come off the treatment. So with this context, I'd love to talk through the therapeutic landscape right now, at least our approved therapies that we're using right now in the clinic.

So first and foremost, we have to acknowledge dupilumab, our first real targeted treatment and that in our IL-13 is now the mainstay first-line for atopic dermatitis, and that's primarily because of the excellent safety profile. They don't have broad immunosuppressive effects. So in this disease, safety is paramount. And one thing we have to keep in mind, I'm an adult dermatologist, and I know a lot of our need is in adults, but a lot of this disease burden is in children, where safety is even a higher bar.

That being said, with these biologics, we know the targeted monoclonal antibodies, there can be variable response. Remember, in the -- depending on which of the dupilumab trials you take a look at, about 30% to 60% of patients don't hit EASI-75, which is a high threshold of clearance of the skin. Also, patients have to be comfortable self-injecting themselves with subcutaneous medications. And that just adds to patient hesitancy, requires a lot of handholding from our staff. And then finally, they do have side effects. So if you look at dupilumab, the IL-15 inhibitors, in particular, conjunctivitis, injection site reactions, these are all things that come up when you talk to patients about this.

Now for the patients who want an oral medication or essentially are reaching for a little bit more efficacy, the JAK inhibitors have become really, really helpful tools in our toolkit. That being said, we have to acknowledge their limitations. They have a really hefty black box warning. That infections -- you have to talk about infections, blood clots, death. You can imagine this really adds to the hesitancy that patients have about starting them. And then they require regular blood monitoring, which again, just another barrier to patients willing to start this.

And so I do think that with all this here, there is a tremendous need for additional treatments for atopic dermatitis, especially those that can address some of these aspects of the disease I just mentioned. So first and foremost, we have to acknowledge that there are a lot of patients who don't respond to any of these first or second-line therapies or have some side effect or contraindication to them. So we always need something with a novel mechanism of action that can capture some of these patients and rescue them. So that's just very, very clinically important. But you can take this a step further.

I'd say that imagine that you're a fly in the wall for one of these conversations with these patients where they're first indicating their interest in moving beyond topical therapies, trying to get into a systemic therapy. And I think the most frequent refrains you'll hear are something along the lines of, "hey, is there a safe pill that I can try for a while" or very rational questions like "if I start this medicine, am I stuck on this for the rest of my life? Or what happens when I stop it when I decide that I don't want to take it anymore." And so we're in this current landscape, having a lot of these nuanced conversations about trade-offs.

And we are talking about potential side effects, blood monitoring, or if you're talking about the JAK inhibitors or if you're being really honest, you just say, gosh, we have great data that if you stop this medicine, you have an 80% chance of flaring and needing some sort of rescue medicine potentially within weeks. So that's where we're at. And I think if we take a step back, we are in a far better place now for atopic dermatitis. And when I first started when we were just using conventional immunosuppression. But that being said, I think our patients are asking us to do better. And that's why I think it's so important that we have clinical trials like this and in development of treatments like soquelitinib that can offer more to this really large and important patient population.

So with that, I'll jump into the study design and clinical data that we're presenting here at the SID. So here's the study design. This is a randomized placebo-controlled blinded dose exploration study looking at soquelitinib for moderate to severe atopic dermatitis. You can see here that we have 72 participants and that's kind of the standard entry criteria for moderate to severe atopic dermatitis that is focused on adults here. Patients who are required to fail the prior topical or systemic therapy, and that will come into play later when we talk about the prior systemic exposures.

So for the first 2 cohorts, Cohorts 1 and 2, patients were evaluated for soquelitinib at the same total daily dose, but either at split or once-daily dosing. And then Cohort 4 essentially doubled that dose to evaluate them at the highest tested dose in this trial. Cohorts 1 through 3 were randomized 12 patients to active treatment and 4 patients to control, and they were treated with just 4 weeks of active treatment. Cohort 4 here, I'll kind of point out is an interesting one. There are a total of 24 patients in this cohort, they were randomized 1:1 active and placebo. And then these patients were actually evaluated for 8 weeks of total duration of treatment. So giving us a peek at what happens with an extended course of treatment.

So here are our patient characteristics here at baseline. And you'll see here, these are cohorts 1 and 2, Cohort 3, a pooled Cohort 1 to 3 and then the Cohort 4, which again, those are the patients that received 8 weeks of total treatment, so twice as long as the other 3 cohorts. Kind of if you just look closely at the actively treated patients versus the placebo-treated patients, you'll see they're actually well balanced between them in terms of baseline demographics, baseline EASI scores and proportion of prior systemic therapy exposure.

One of the things we did observe is that as we got into cohorts 3 and 4, the baseline EASI severity actually crept up. And we think that's basically due to the nature of the recruiting sites that activated by that point in the trial. I think one interesting point about this trial population is a fairly high proportion of patients who are exposed to systemic therapy. So more than 1/3, which is not the case in many of these atopic dermatitis trials. And most of those prior exposures were dupilumab, but with the representation of other AD systemic therapies.

So let's jump into the efficacy results. This is seen here for cohorts 1 through 3. So recall, these are the patients treated for 4 weeks of total dosing. And we'll take a look here for -- sorry, cohorts 1 through 2, looking at EASI-75 and IGA 0/1. So these are really important endpoints. They traditionally have been co-primary endpoints for pivotal trials for atopic dermatitis. And we can see for the lowest tested total daily dose, cohorts 1 and 2, we're actually starting to see patients hit these responder thresholds at just 4 weeks.

And then if you take a look at Cohort 3, these are the patients who received double the total daily dose compared to cohorts 1 and 2, you'll see an even more impressive EASI 75 and IGA 0/1 responder rate there, particularly if you look at EASI 75. And notably, for these patients, none of the placebos were able to hit any of these responder thresholds. If you take a look at EASI 50, EASI 90 and the mean percentage reduction in EASI, you'll see very similar directional results with improving scores for Cohort 3 at the highest dose, especially when you compare to placebo.

So here's a plot of the mean percentage reduction in EASI for cohorts 1 through 3. And what you'll see here on the vertical axis is the actual change in EASI percent from baseline. And then horizontal axis is time, of course. And then I'll just point you towards that middle white period. This is the actual 4 weeks of active treatment that these cohorts 1 through 3 patients received. And all the way on the right in the gray here is a 30-day follow-up period off any active treatment. So they're followed up 30 days after the last dose to see how their skin and safety is doing.

So in orange here is the placebo group. This is a pooled placebo group from cohorts 1 through 3, and you'll see them in the top curve there. And then in blue and red here are cohorts 1 and 2. Again, these are the patients that got treated with the same total daily dose. And you can see that their curves overlap almost perfectly. And they do start to separate from placebo. You can start to see that occurring at day 15, and that becomes very apparent on day 28.

So here's the really interesting part about this trial. At the follow-up, you actually see maintenance of that clinical response. So I was involved in the other trials for JAK inhibitors and other therapies. This is something that you don't often see in atopic dermatitis where the disease frequently comes back after treatment. And then in Cohort 3 here in the green, what you can start to see is a dose response. So these are the patients treated with double the total daily dose. You have an earlier and deeper response. You can see it as early as day 8, statistically significant, day 28 and again, that maintenance of response here.

So we would love to double-click on that part of it because as a clinician, that's what really popped out to me with those data. First of all, the efficacy, of course, the rapid deep response, but also this durability. So what's interesting in this slide is that this is a real focus on Cohort 3, and these patients unique to this cohort were followed up to 90 days after the last dose. And so what we can see in this cohort, you have that early deep response, but then you actually have durable maintenance of that improvement all the way to the last date of follow-up. So we actually don't see deterioration even through the last follow-up visit. So we don't know how long this persists because we've ended it and it's continuing.

So I don't want to steal Dr. Sarin's thunder because she's going to help us look into the biomarker and potential mechanistic explanations for this durability. But I will just point out too, if you really look at this Cohort 3 population, you'll actually see that they have increased T regulatory cells in the blood, and that's especially apparent when you compare them to placebo in the lower dose treated patients. So if you recall from the mechanism, we know that ITK's activity is shifting us from Th17 inflammation over to those T regulatory cells. So that could provide a potential mechanism for why we see this clinical durability.

So this is just a reminder of what happens in real life when you treat patients with other medications with this rebound or worsening of the skin disease. So these are 3 of our approved therapies and just an example of an investigational product. So the JAK inhibitor is kind of a classic example, highly efficacious. But in the clinical trials and just clinical experience, you can see once you stop the medication, that skin improvement starts to deteriorate pretty rapidly, oftentimes within 2 to 4 weeks. And then just anecdotally, my patients tell me that they miss a dose, they'll feel that itch is starting to come on even before the signs start to change on their skin.

Even with dupilumab, which is a biologic, we know from the SOLO continuation studies and just from clinical experience, this is where day 0 is actually when they completed their 16 weeks of dupilumab and they were randomized to other doses of dupilumab or essentially stopping it by being switched to placebo. And you can see that deterioration in the skin control at that point as well, seeing hints of that as early as 4 weeks, but definitely by 8 weeks. So this is just one more example of another investigational product, the STAT6 inhibitor. And what you can see there is that at the end of treatment, you can start to see some of that clinical deterioration as well.

So now let's take a look at Cohort 4, and I actually really love this slide because this gives us a sneak peek at what happens if you try to extend the duration of therapy. So Cohort 4 is unique in this study. These are the patients that got 8 weeks of active treatment, again, a 1:1 randomization active to placebo. And then here, we see the highest degree of EASI 75 and IGA 0/1 response.

At this 8-week treatment duration, we are seeing some patients in placebo hitting EASI 75, but very, very low compared to the actively treated patients. And we see directional results in the same manner, EASI 50, EASI 90 and a mean reduction in EASI. But again, just really pointing out, 75% of these patients are hitting EASI 75, which is, as a clinician, something you're really excited about. At this treatment duration as well, we're starting to see the placebo patients flare as defined by requiring rescue medications. So we had a couple of patients that flared here and none on the soquelitinib treated.

So just plotting out here the response curves. And what you can see here in orange is the placebo group. And then what we see is this continuing to deepen response curve for the Cohort 4, again, highest treated dose. Also the longest period of treatment and then that clinical durability seen again at the end of that treatment period. And of note, I will point out that, that slope does not start to plateau. So at 2 months of treatment, we do not see a plateau in the improvement of the EASI scores there.

So this slide, I think, is very illustrative if you're just trying to take a look at all the different cohorts in kind of their EASI 75 and IGA 0/1 response. So on the left here, we're taking a look at cohorts 1 through 3, again, treated for 4 weeks. And in the solid bars here, we can see the EASI 75 responder rate. And then in the striped bars, we can see the IGA 0/1 responder rate. So you can see in this pooled Cohort 1 to 3, at the end of just 4 weeks of treatment, we are seeing EASI 75 and IGA 0/1 response. And then interestingly, that is maintained day 30, day 60 and day 90. And again, we are not just cherrypicking the responders here. This is a total population and maintenance over that time frame. And then Cohort 4, what you're seeing here is, again, longer duration of treatment. You have a superior EASI 75 and IGA 0/1 and then maintained at the 30 days of follow-up.

So we then asked the question, so what happens to the folks who've had prior systemic therapy exposure? Again, a kind of a marker for more severe disease or tougher phenotypes. And this pools all 4 cohorts together, so you can see the placebo group versus the soquelitinib treated groups, and you see a separation of the curves in terms of mean percent reduction in EASI. And then over here on the right panel, you can see the patients with prior systemic exposure. So even that placebo group is only the placebo-assigned patients who had prior systemics and actively treated patients with prior systemic exposure. And you can see it continues to have that separation of the curve, suggesting good activity within these patients with prior exposure. And this is the one I love as a clinician. So this is the folks who knock on my door. These are the patients with prior systemic failures.

So taking a look again at the patients with the highest total daily doses, they were able to identify 6 patients with prior systemic failure. All of these patients have failed dupilumab, many additional agents, including some with a couple of failed agents. And what they were able to see is 3 of those 4 patients actually improved on soquelitinib, 2 markedly so. And both patients who were assigned to placebo ended up flaring, again, requiring rescue medications. So I think from a clinical perspective, this really gives us a lot of excitement about the potential activity of soquelitinib in patients with prior treatment failures.

So just turning over to a summary of our safety here. This is taking a look at cohorts 1 through 3, again, 4 weeks of active treatment and then Cohort 4, which is 8 weeks of active treatment. And what we can see is that the frequency of adverse events is well balanced between active and placebo-treated patients. Actually, in the folks with the longest exposure, placebo ended up with more adverse events. There were no severe or serious adverse events and no patients discontinued due to AEs.

So here's the granular safety table. And again, taking a look at cohorts 1 through 3 and then Cohort 4, the longest exposure. And kind of the big takeaway here, again, a mix between placebo and actively treated patients, again, pretty well spread across. Most notably, there was no hematologic or laboratory abnormalities, and there was no infectious signal in the safety data. Some patients treated with soquelitinib reported a headache. Apparently, that all occurred at a single site and most of them were transient, lasting less than a day. So hard to read into that. But overall takeaway, a really clean safety profile, especially from our interest with relation to infections and lab abnormalities.

So in conclusion, we present our Phase I clinical data about soquelitinib. We are really excited about this ability to target Th2, Th17 inflammation and also potentially start to shift into these T regulatory cells for atopic dermatitis. So far, we see a clean safety profile, no infection signal, no lab abnormalities. And again, we can attribute that to the tissue selectivity of this medication. We saw an early and deep response with a relatively short dosing period of just 4 to 8 weeks. Again, this is a Phase I trial. And again, that speaks to the broad targeting of Th2.

And we also see durable treatment effects with patients with prior systemic exposure, including prior systemic failures. And so finally, just I think we'll tee up my colleague, Dr. Sarin here. We're really excited about this mechanism. We think that this might actually provide promise for other conditions with autoimmune inflammatory disease, especially with this potential mechanism of rebalancing immunity. So thanks so much.

So given the time, I think we'll hold questions until the end. It's now my great pleasure to introduce Dr. Sarin. But before I do, I always like to say that, you know I have something else to add. Before I do, I always say it starts with the patient. What do we observe in the patient? We observed clearing of skin lesions. We observed safety. We observed a durable effect. And then we go into the laboratory and we say, okay, well, how do we explain this?

And one of the things I think you're going to learn from Dr. Sarin is the translation here is absolutely beautiful and portends for, I think, I believe, success not only in atopic dermatitis, but many other diseases as well. So I'm really looking forward to your talks, Kavita. And I also understand that following Albert is difficult.

Thank you, Richard. Thank you, Albert. That was a great talk and really excited about the clinical efficacy. But I get to present the really fun stuff, which is what is happening underneath the skin that explains this clinical response. So it gives me great pleasure to present the immunologic data from soquelitinib for atopic dermatitis. And Richard did such a beautiful job going over the mechanism, but I do want to just highlight it one more time so that this is the basis of all of the studies that we'll be presenting so that everyone is on the same page.

So as Richard mentioned, ITK is a T cell signaling kinase that's primarily expressed in T cells, NK cells and ILC2 cells. And ITK plays a critical role in mediating TCR differentiation and TCR signaling. But what's really important to understand is that ITK is not equally required across T cell programs. Genetic studies have shown that loss of ITK preferentially suppresses Th2 and Th17 responses, but spares immunoprotective Th1 responses, and that is due to the compensation from a related kinase called RLK. The second important thing to know is that ITK plays a critical role in immune switching between Th17 and T regulatory cells. Loss of ITK has been shown to shift cells away from Th17 programs into Tregs.

And as Richard mentioned, that is the beautiful design of soquelitinib, which was designed to suppress selectively ITK, but spare RLK, thereby suppressing Th2 and Th17 immunity, but sparing Th1 so that we retain protection against cancer and other infections. And this biology is central to atopic dermatitis, which is primarily driven by type 2 inflammation. And as Albert mentioned in his beautiful introduction to the landscape of therapies, many of the therapies that are currently very effective for atopic dermatitis suppress these Th2 cytokines in this pathway, IL-4, IL-13 and so on. And they are effective, but they're not necessarily durable, as Dr. Chiou mentioned.

ITK inhibition is happening just upstream at the T cell programming to shift away from Th2 and Th17 programs and so really can lead to more of an immune reprogramming or a shift to suppress these downstream cytokines. So Dr. Chiou also did a great job going over this. I'm going to be extremely brief and summarize the whole trial in one single slide. So this was a Phase I placebo-controlled study and patients were enrolled in 4 cohorts. In the first cohort, patients were treated for a total of 4 weeks at increasing doses of soquelitinib. And in the fourth cohort, patients were treated for a total of 8 weeks at high-dose soquelitinib 200 milligrams twice a day. Now for this talk, I want to draw your attention to 2 things. The first is that it was placebo-controlled, but the second is that every cohort had 30 to 90 days of follow-up off of treatment, which allows us to look at the durability of response.

And I'm also going to summarize all of the work that Albert just presented into a single slide, which really highlights 2 things: the clinical efficacy with a significant improvement in EASI scores in 4 to 8 weeks of treatment. And the second thing, which is the durability. If you look at both 30 to 90 days off of treatment, none of the patients had a recurrence of their atopic dermatitis, no one had a rebound and no one required any rescue medications. And this is why it's so interesting to peek underneath the skin and see what is happening immunologically.

So from an immunologic standpoint, we investigated the effects of ITK inhibition on Th1, Th2, Th17 and Tregs. And the assays were looking at serum cytokines, blood flow cytometry and PBMC single-cell RNA sequencing. And this is the first finding. Soquelitinib reduces Th2 biology. On the bottom left is PBMC data showing a dose-dependent reduction in proliferating Th2 cells. The Th2 cells are down. On the right, we see a significant reduction in Th2-related cytokines, IL-4, IL-5 and IL-13. We also see a reduction in TARC, a Th2 chemokine, which is directly associated with the activity of atopic dermatitis. But I want to call your attention to the gray shaded area here to highlight a very interesting finding, which is that even 30 days after treatment, so during the drug-free period, the cytokines continue to decrease.

The second interesting finding is that soquelitinib led to an increase in persistent Tregs. On the top here, you can see that soquelitinib led to an increase in Tregs marked by CD4 positivity, CD25 high and FOXp3 as compared to placebo in the high-dose group, the 200 milligrams twice a day as well as the Cohort 4. But here's what's really interesting. Those Tregs continue to persist after the drug -- 30-day drug-free period. And this may actually explain the durability of response that's seen clinically.

And when we look more closely at the Th17 Treg axis, we see the following. Soquelitinib increased BACH2, which is a transcription factor that's involved in promoting T cell stability and Treg stability and longevity in the high-dose group. So on the bottom left here, you can see increased batch 2 expression in the high-dose group treated with soquelitinib as compared to placebo. And conversely, treatment with soquelitinib led to a decrease in RORgamma T, a master transcription factor for Th17 cells. So this suggests that soquelitinib may be playing a direct role in regulating that Th17 Treg axis. So what is one potential mechanism behind this? Well, one is that ITK has been shown to sequester batch 2 in the cytosol through downstream phosphorylation and inhibition of ITK by soquelitinib may release BACH2, so it can translocate into the nucleus and induce transcription of genes as FOXp3, promoting Treg longevity.

The third finding, which is relatively unexpected, was that soquelitinib led to inhibition of the JAK-STAT pathway. On the top, we observed that SOCS3 expression increased in circulating T cells, including Th2, Th1 and TC17 cells. On the bottom right, we observed that JAK1 signaling was suppressed as along with STAT6. And this is important because, as Albert mentioned, the JAK/STAT pathway is central to atopic dermatitis and STAT6 is central to IL-4 and IL-13 signaling. And this was somewhat unexpected because ITK is not known to play a direct role in the JAK/STAT pathway. So we believe this may be happening through sort of the T cell immune reprogramming away from Th2 and Th17 programs. And it is also important because that suggests that maybe this JAK/STAT inhibition may be more selective in the T cell programs.

So in conclusion, soquelitinib is an oral selective covalent inhibitor of ITK that spares the related kinase. And it appears to be rebalancing Th2 and Th17 responses, suppressing Th2 and actually shifting Th17 responses towards a Treg program, with persistent Tregs even after the drug is discontinued. It also appears to inhibit the JAK-STAT pathway in the T cells. And together, this may explain the durable remission that's seen clinically as well as its favorable safety profile. But more broadly, this really highlights a new paradigm for treating inflammatory conditions. Target upstream at the T cell differentiation node shift away from the inflammatory T cell programs while preserving the immunoprotective T cell programs, reprogram immunity and the potential for durable control.

And with that, I'd like to turn it back to Richard.

As I told you, seldom in my experience in medicine, do you see such a consistent translation where all the things just sort of line up with the proposed mechanism of action and more importantly, the clinical findings. So that's really beautiful. So I have the task, and I want to go quickly because I do want to leave time for questions. So why are we excited about soquelitinib? It's very simple. We may be modifying the underlying biology of the disease, okay? We're not just blocking a cytokine or blocking a receptor. We're changing the disease. We're disease modifying. That is a big, big statement and it can be -- if confirmed in other trials and other diseases really does change the paradigm, as Dr. Sarin's last slide mentioned.

Now it's even better than that because do you realize that those Tregs are antigen-specific? Okay. They're not just suppressive. A Treg has a T cell receptor and is only suppressing a particular antigen response. Did you realize that the Th2 cells that were decreased were, as she said very cleverly proliferating Th2 because we can figure that out with our science. So it's not just blocking every Th2 in your body, it's the proliferating ones. Those are presumably the ones that are associated with the ongoing inflammatory reaction.

Okay. So the precision, she's an expert in precision medicine is really amazing. So we may be modifying the underlying biology, and that represents a new way to think about therapeutics, treatments, monitoring, et cetera. And what is -- and is it worth it? You bet it is because I don't know of any patient who wants to take a drug forever. Every drug has side effects. Every drug has chronic implications that may take years to figure out. Most people want to take a drug for a while and go off of it, hopefully never come back. If it does come back, do it again.

My own personal experience as a physician at Stanford treating patients with Rituxan was patients got 4 weeks of Rituxan, then it went to 8 weeks. Then 70%, 80% didn't need it again for 30 months. But when they came back, guess what, they wanted it again. And they wanted it again after that. And I had patients in my clinic who I gave Rituxan to 10x because it worked, it was well tolerated, and it gave them a good remission. They didn't have to take pills and come in and do all kinds of stuff. They had a simple infusion, they were done.

So new paradigm, we're modifying the disease. And I don't need to go through the details here. You've already heard blocks Th2, Th17 rebalances Tregs. I do want to emphasize that those Tregs are not just suppressive. They're antigen-specific suppression. That's why it was a Nobel Prize last year in medicine, not for me, unfortunately, but for the people who have discovered it. The profile for us now that's emerging, I want you to think about this, is a shorter treatment period. 28 days gave you a durable response. Maybe a longer duration will give you even more durable response. That's a question that will need to be answered. Remissions are durable. We see activity in people resistant to treatments, not just had other treatments, but failed a dupi and a JAK inhibitor in one case, cytotoxic.

So we may be in an era where maybe we don't need to treat you for a year. And unfortunately, you stop your drug in a year and 2 weeks later, the disease is back. Okay. If you look at all those studies that Albert alluded to, the rebound occurs in 4 weeks or less. That's why we didn't have to follow patients for more than that, really wasn't worth it. We weren't seeing any rebound. And every other agent, the rebound occurs within a couple of weeks.

And then finally, just again to remind you, we are enrolling a Phase II randomized double-blind trial in atopic dermatitis. So really quickly on that trial, I've shown this before, 12 weeks of therapy, moderate-to-severe AD, very similar to the patients that we just described to you, 4 arms, placebo, 200 milligrams QD, 200 milligrams BID, 400 milligrams QD. So we are looking at QD dosing and of course, the placebo, they're equally balanced. It's completely randomized. It's a global study. The primary endpoints will be the typical what's your EASI score at 12 weeks and then, of course, the other secondary endpoints. And this study is now ongoing. We expect to have data from this study around third quarter of 2027.

Now we have a very important collaboration with a company called Angel Pharmaceuticals. I'm pleased to announce that Dr. Charles Lee from Angel. He's the President of Angel. He's my boss. He's here with us today. Charles and I and the team at Corvus and the team at Angel work very closely coordinating research and development. Angel has the rights to soquelitinib in China. We have the rights in the rest of the world. And this is the study Angel is doing. It's pretty similar to what we've been doing, 12 weeks of therapy, moderate-to-severe AD, there are 2 cohorts. It is placebo-controlled.

We think placebos are important in this disease, even for the laboratory measurements. And basically, 100 milligrams BID, 200 milligrams once a day, placebo, we can look at the data then, then they go into the next cohort, 200 milligrams BID, 400 milligrams once a day, placebo. We will have data from the first cohort, Charles tells me or I guess he's going to be in trouble by the end of the year. The Angel team is doing a spectacular job. Again, we work very closely with them. We have conference calls every week, going over patient selection and information and so forth. And once that's completed, the study automatically rolls over to Phase II, 60 to 90 patients treated, again, with a placebo treated on 1 or 2 of the doses that are studied.

So again, sort of to summarize, we think our results show that soquelitinib could become, I say leading oral. I mean leading therapy. It is oral, but I think a leading therapy period for atopic dermatitis and possibly other diseases. And I won't go through all these diseases. We have positive clinical results. We have shown safety. We see deep responses, including in patients who are refractory to other therapies. That is very challenging patients. We see durability consistently. Now is that going to -- are we going to see 100% durability forever? Probably not. I'm sure that there's going to be patients who fail at some point in the future, but we haven't seen it yet. And we have, I think, identified immunologic parameters that support the mechanism of action that are going to teach us more that are already informing our second and third-generation compounds.

Okay. This is an iterative process. Take the patient, go back in the lab, make better stuff. And I think there is a possibility of coming up with biomarkers that maybe will predict who does well, who needs -- who has the more durable responses. Maybe it's a Treg, maybe it's a cytokine from the Treg or something like that. So there's a lot of work to do, but we have something very special, and we're all over it. So finally, I use this bull's eye slide to remind myself, I look at this every night that it's the target. It's all about picking the good target, a target that has applications to a disease that's relevant and hopefully more than one disease. And we've been able to make a very specific drug, the aha moment, the inventive step, go for specificity over potency.

We used to argue, "hey, this one is more potent," but I would say, "yes, but it hits RLK, okay." No, I don't care about the potency as much. I like that, but I want the selectivity. I want both to get that. And as you can see here, Phase III in lymphoma, Interim data from the lymphoma study later this year. I forgot to mention Angel data, maybe I did mention late this year. So we're really looking forward to the Angel data in their Phase II later this year. Angel is also going to be starting an asthma study, and I know they're preparing to file an IND on that as we are. And then I think you can see the rest of the opportunities here. ALPS, I didn't have time to talk about that. We are planning to present -- hopefully present some of that data at the ASH meeting in December. That's a very interesting disease. Very rare disease, but very interesting, again, teaching us a lot, autoimmune lymphoproliferative syndrome, bad disease.

And finally, our upcoming milestones. Phase II HS study, asthma by end of year, Angel data late 2026, ALPS data, ASH, Phase III interim data later this year and lymphoma. Those are the near-term milestones for Corvus. And so with that, let's open it up. Maybe Dr. Sarin and Dr. Chiou can come to the front, and we'll answer questions. I think we'll take the questions from people in the room, and then we can also open it up to the webcast.

So any questions for any of us? Mostly ask Albert and Kavita because they're smarter. Graig?

Graig Suvannavejh from Mizuho. I think investors who look at this data see it as early. It's promising, but it's early. We've got other programs that are out there as well. So -- and there were some references to JAK inhibitors and STAT6 and perhaps some other mechanisms of action. But as -- maybe for Dr. Chiou, as you are involved in many clinical trials right now, as you see the ITK inhibition mechanism of action relative to the other mechanisms of action, is there any other aspect of what you're seeing with soquelitinib that beyond maybe the prevention of rebound or having long durative efficacy, at least at this stage. Is there anything else that you would point to that helps to differentiate this versus some of the others where investors seem to be paying attention to equally, if not more so?

Yes. Thanks for the great question. Honestly, I was holding my breath for the safety data to come through. I think just like I started with, I think safety is paramount in this disease. I think a lot about these pediatric patients that will eventually need something. And then on that particular point, it's great that we have dupilumab, which is a great treatment, but it's an injectable, which for kids is a big deal. So a safe oral medication, I think just that alone is something right there. I think the efficacy data, yes, really, really early. But just so promising, right, especially looking at that 2-month dosing, the 75% of patients hitting EASI 75. I mean, you can put that up against most of these really promising investigational agents that are coming through right now.

So I think in terms of oral medication where you have just checking that safety box, at least from what we know, and again, really hoping that holds up in later phase trials with that real promise of the efficacy, it's fantastic. Honestly, durability is so fascinating, that was icing on the cake, right, to come in after that. But I was talking to someone earlier, if you kind of look at that cohort 4, 2 months of treatment and then maybe 30 -- sorry, 90 days of durability, I apologize that's Cohort 3. That's like about 6 months, right? You can imagine, even if that's the worst case and just that durability plummets at the end of that, like 2 courses a year and that sort of response for AD. Boy, that's a great conversation to have with the patient.

Thank you. Next question.

First of all, I think the durability issue is getting back to the last question. Nobody wants to take this medicine continuously. And so having the durability is the thing that really distinguishes us. It's amazing. So -- but I noticed that you -- that the highest dose also was the only dose that had blood levels of Tregs. And also, it seems like the more you go out, the longer the durability. So what are your plans for? Is it possible then to take it 2 months for a year? And what do you think about that? I mean because that is a game changer.

Thank you. First of all, we should not let that person in the room. He's a professional. But can I take that? So Tony, Dr. Oro, the -- this is the data we have now. So 1 month gives us Tregs that persist at this dose, 2 months gives us Tregs that persist. I think a real question now is does longer treatment give you even greater durability? Maybe you don't even need to give it for 28 days. In animal models, you don't need to give it that long, and you may induce this. So that's another thing to think about. Can we even go shorter and generate the Tregs. So we don't really know the answer to that.

But in animal models where we can be a little more -- we can do more biopsies and look around. There's no question, you see Tregs infiltrate lesions, skin lesions very quickly, and same thing in asthma models. And so that's new biology, and I think there's going to be a lot of clinical questions. But I think from a clinical development standpoint, not to worry. I think the clinical paradigm for approval would be 4, 8 or 12 weeks of therapy, placebo-controlled, what's your EASI score. Now if you want to claim I can retreat somebody a second and third time, I think you are going to have to go in the clinic and prove that. But that's been done before with dupi and so forth continuation studies.

But the question was, why is it different from anything else? And then it's -- I mean, that's the answer is that it's the durability -- non-injectable durability is a game changer.

Yes. Thank you for that comment. Any other questions? Zack?

Yes, we have a couple from the webcast here. So I'll start with one from Paul Choi from Goldman Sachs. For the doctors, what sort of duration or study size is needed to establish the benefit risk profile as safe?

Yes. So that's a great question. So I think one of the things that maybe we'll have to talk about is the duration of the clinical trial, right? So this Phase I for a lot of the patients, only 30 days of follow-up after that dosing period. I think what we're seeing is that there is a pharmacodynamic effect that's persisting with that durability, which is a great finding in this trial. But I think we do have to follow these patients out many months. And I'm starting to think about the other trials that have been run for, say, the biologic trials or others to just get a sense of that safety over that full exposure period of months after the last dose, which is a great opportunity as well to further evaluate that durability aspect of the medication as well.

I know that as we've been talking about the next phase trials, a lot of that is powered around kind of efficacy endpoints as well. So I think maybe if you want to touch upon some of those considerations. But at least what I'm thinking about is this drug is really interesting even after you stop the last dose and that having some of that safety follow-up for -- throw out a number 6 months afterwards, et cetera, just really understand what's going on there. Because again, we haven't seen the end of the durability yet, at least from these initial phase trials.

I don't know maybe if Paul has a follow-up question on that. So because I wasn't sure whether he was asking about the safety in the off-treatment period or the on-treatment period. I mean both are important. But I forgot to mention that in the follow-up period, the study is still blinded. So the patient and the doctors still don't know what they're getting during the follow-up. That's an important point. One other point as long as we're talking about placebos and controls is, as you can see from Dr. Chiou's safety slides, there's really no side effects that are worrisome to the patient. The placebo and the treatment were identical basically. And this is an oral medication.

So when we say the trial is blinded, it really is blinded. So just think about if you were taking a drug that had injection site pain. And let's say it was 60% or 70% of patients. Well, that's not really a blinded trial because you know the patient knows that they're getting the drug. And I see this -- to me, this disconnect in some of these trials where you got 20% of people getting conjunctivitis, you've got 60% injection site abnormalities and they occur every time. And so how do you blind that? Well, the answer is it's not really blinded.

Now I'm not criticizing that it's the best you can do. I mean I think those studies are doing the very best they can do. But it really does raise the question. But when we say blinded, I can tell you because I've swallowed some of those pills, they're not different, okay? I don't want to do it for a year, but it's -- they're not different. And it's impossible to know what you're getting. So it really is blinded.

Anyway, any other questions from there?

Yes. We can move on to another one from Li Watsek from Cantor. This is a 3-part, so bear with me. Immune marker cytokines were lowered in the drug-free stage. What would be the explanation for that? Do you see that reduction from the placebo arm? Next, can you discuss what you saw in placebo arm in terms of rebound and biomarker changes? And then last, how does the biomarker data read-through to other potential indications for soquelitinib, the asthma trial, HS, et cetera? Can we expect to see similar durability effects?

Okay. So I hope I can remember the 3 questions. The first question is the reason the cytokines are still falling in the drug-free period is because there's Tregs around and the immune response is still being inhibited. So that's our explanation for why they continue down. Now you'll notice they bounce around a lot, cytokines. Measuring cytokines in these patients is very difficult because the timing is difficult. I mean every patient is a little different. You don't know when the optimum changes are occurring. Some of these cytokines are very short-lived, like I think IL-4 has a plasma half-life of 4 hours. So you can easily miss these things.

We are noticing interesting things like IL-5 drops early, IL-4 later. Now what is the explanation for that? We're not sure. Different subsets -- as Kavita mentioned, different subsets of cells being affected differently. So the answer to the question number one, the cytokines continue to drop because of the ongoing Treg-induced immune regulation. The second question on placebos. Placebo cytokines jump all over the place and really don't give you any constant stuff. They could be down, they can be up, they can be down, they can be up. It's just really -- I didn't show that really for the sake of simplicity. You certainly don't get a consistent thing in a drug-free period. There's no question about that.

Now the rebound question on placebo, if you remember those slides that Albert showed, placebos don't rebound. I always get asked that question, how placebos do? Well, because they don't respond that well. Remember, we had 0% EASI 75s and you didn't get any drug. So how -- in cohorts 1 and 2. And so when you -- if you don't have much of a response, it's hard to rebound. And they're not getting treated with anything. So whatever the mechanism of rebound is in a JAK inhibitor or dupi or a STAT6 inhibitor, whatever that mechanism is, I wish I knew what the mechanism is, but I don't think anybody knows. But it's really striking how quickly it occurs within a couple of weeks, if you look at those curves. So anyway, we -- the question of the placebo rebound is sort of not really addressable because they don't rebound. There's nothing to rebound to. And then I think the other question was...

The read-through for other indications.

Well, we think the read-through is good because -- and that's why we're doing an asthma study, which, again, is thought to be Th2-driven and all the cytokines and things that we're thinking of are important in asthma. Now we are going to do something a little different in asthma, and that is, given our mechanism of action, we do not need to restrict it to eosinophilic asthma. So let me say that again, that's double the population, if you don't -- roughly, because half the patients don't have eosinophilia.

And so most asthma studies require an eosinophil count of 300 or sometimes 150. That is eosinophilic or allergic asthma, we're going to open that up wider. And so I think the read-through is -- all I can say is that we've now looked at many different animal models, inflammatory bowel disease, asthma, psoriasis, atopic dermatitis, graft-versus-host disease, systemic sclerosis. I may be forgetting a few, but -- and we see consistent efficacy, robust effects in all of those diseases.

Okay. Next one from Etzer Darout from Barclays. Have you also looked at the placebo group EASI scores in cohorts 1 to 3 out to day 118? And also, do you have 90-day off treatment for Cohort 4?

So let me take the last one. We don't have 90-day treatment for Cohort 4 because we recognize that we didn't really need to do it. First of all, you got to realize to do this requires an amendment to your protocol, IRBs and you also have to pay for this. And we were comfortable enough with what we saw with the Treg data from Cohort 3 and from Cohort 4 to say, okay, let's take our resources and double down on this in the Phase II trial, which we're doing and where we will have 90-day follow-up, okay?

Now placebos, placebos flare. If you follow them in these drugs, I don't think we went over the flares, but I don't think we've ever seen a flare in a treated patient, but we do see it in the placebos. So if placebos bounce around, as you know, also remember another thing about our trial. Somebody else, I think, Graig, you asked this question. I would argue that the patient population we have is sicker than most of your AD studies. Why do I say that? First of all, 35% of prior therapy, 8 patients have failed. I mean are refractory to prior therapies. Nobody takes those. Nobody takes those patients.

So when you talk about 1/3 of the patients and half of those are refractory in a study with only 50 subjects, that's a pretty big hit potentially. And so yes, I mean, we don't have 1,000 patients and you need to do that at some point. But we have a very robust clinical experiment where we took patients who were pretty sick and we had -- and we saw efficacy. And that's what motivates us to go on. Look, I think that the data we've shown in a sicker patient population is as good as any data, any product under development I've seen and even some of the ones approved, albeit they have hundreds or thousands of patients. So that's why we're excited about this. It's what we're doing.

Okay. Next question from Sean Lee from H.C. Wainwright. Seeing the inhibition effect on JAK/STAT pathway, would that potentially lead to safety issues long term? And does it matter to tease out the treatment effect from that -- from the Treg effect? Or does it not matter?

Okay. So I'm glad that he asked that question because I forgot to mention that, is that, remember, it's not like we're blocking JAK/STAT in every hematopoietic cell, okay? It's only in the cells that have ITK and probably only in those activated T cells. So it's very restricted. Now again, the fact that we're seeing changes in the JAK/STAT pathway, it's not because our drug is interacting with ITK. Let's make sure people understand that. Our drug does not bind any JAK, JAK1, 2, 3, no. So this is an indirect effect. And it's due to the fact that -- and it's very clear in the patients that we treat with soquelitinib, SOCS3. SOCS3 stands for suppressor of cytokine signaling 3. It is one of the brakes. Remember, the immune system has gas pedal in a brake.

So SOCS3, when you're trying to shut down an immune response inhibits the JAK/STAT signaling because you're trying to cool things down. So we're seeing patients' inflammation go away. We're blocking T cell signaling upstream. Naturally, SOCS3 goes up. SOCS3 is going to block those pathways. So it's almost a secondary effect. I don't think it's a primary effect. But again, it's nice to see this biology happening. right? It's nice to see that you're having this multitude of effects in conjunction with clinical responses and durability and all that other stuff.

But just to be clear, we're not a JAK inhibitor because we got, I don't know, some guys out there saying, "Oh, we're a JAK inhibitor." No, no, no. We're not a JAK inhibitor. We don't bind JAK. No binding to JAK. We affect SOCS3. SOCS3 will dampen JAK -- some of the JAK/STAT signal, okay? And that's occurring in only the cells that have the ITK target. So that's not happening in your myeloid cell or your macrophage or any other cell. okay? So that's very important. But it's very interesting to see that you really are shutting down this inflammatory response. You got Tregs.

Well, first of all, what do you think Tregs are doing? They're trying to shut down the immune response. Wouldn't it be crazy if the immune system makes Tregs and turns on JAK/STAT signaling. You wouldn't, when you drive your car, step on the brake and step on the gas at the same time. Well maybe, you would do -- but you wouldn't do that. So the immune system is dampening the response, Tregs and reducing JAK/STAT signaling. So that's an indirect effect, but very interesting because yet it's another clue to the fact that we have some very interesting biology going on, unprecedented. Nobody has seen stuff like this before, okay?

Any other questions?

We'll do one more, and then I think we need to wrap up. Jeff Jones from Oppenheimer. Can you speak to what magnitude of change is typically considered clinically significant in regards to Th2 populations?

I will speak in general. Well, I mean, I think that's a tough one. So I believe that Jeff is asking the relationship between the degree of Th2 reduction and clinical response, we just don't have enough data to make those kinds of correlations at this point. But that may be actually something to look at. Listen, we're working really hard looking at all of this, serum cytokine relationships to response, Treg in relation to response, all of those things. It's tough. You can't do -- you're going to need many more patients to make those kinds of correlations.

And what I said, this is human biology. I mean it's highly variable. I mean, as you can see, these patients are -- some are young, some are old, all different prior therapies, et cetera. But that's a great question, Jeff, but I don't think we have enough data yet to come to that. But should you get that, should you come up with the Th2 level that predicts response or duration of response, I would file a patent on that in about 10 milliseconds. Any other questions?

So anyway, first of all, I want to thank Dr. Chiou and Dr. Sarin on really wonderful presentations. I mean that was really exciting. I'm so inspired now. I don't know what to do with myself. But I want to thank the people in the audience here for attending. I want to thank everyone on the webcast. I think that we have some really exciting data that we presented this morning and Dr. Chiou's presentation on Saturday, poster tomorrow. Kavita's poster also this afternoon. Again, you have a chance to come by and hassle her even more. So we look forward to seeing you at these posters, but I want to thank everyone, and we're eager to report on our future progress. Thank you.

Good afternoon, everyone, and thank you for standing by, and welcome to the Corvus Pharmaceuticals Fourth Quarter and Full Year 2025 Business Update and Financial Results Conference Call. [Operator Instructions]

It is now my pleasure to turn the call over to Mr. Zack Kubow from Real Chemistry. Please go ahead, sir.

Thank you, operator, and good afternoon, everyone. Thanks for joining us for the Corvus Pharmaceuticals Fourth Quarter and Full Year 2025 Business Update and Financial Results Conference Call. On the call to discuss results and business updates are Richard Miller, Chief Executive Officer; Leiv Lea, Chief Financial Officer; Jeff Arcara, Chief Business Officer; and Ben Jones, Senior Vice President of Regulatory and Pharmaceutical Sciences. The executive team will open the call with some prepared remarks followed by a question-and-answer period.

I would like to remind everyone that comments made by management today and answers to questions will include forward-looking statements. Forward-looking statements are based on estimates and assumptions as of today and are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied by those statements, including the risks and uncertainties described in Corvus' annual report on Form 10-K for the year ended December 31, 2025, and other filings the company makes the SEC from time to time.

The company undertakes no obligation to publicly update or revise any forward-looking statements, except as required by law.

With that, I'd like to turn the call over to Leiv.

Thank you, Zack. I will begin with a brief overview of our fourth quarter and full year 2025 financials and then turn the call over to Richard for a business update. Research and development expenses in the fourth quarter of 2025 totaled $9.9 million compared to $6 million for the same period in 2024. R&D expenses for the full year 2025 totaled $33.7 million compared to $19.4 million for the full year 2024.

For both the fourth quarter and full year 2025, the increases in R&D expenses were primarily due to higher clinical trial and manufacturing costs associated with the development of socolitinib as well as an increase in personnel costs. Net loss for the fourth quarter 2025 was $12.3 million compared to a net loss of $12.1 million from the same period in 2024. Included in the net loss for the fourth quarter of 2025 and 2024 were noncash losses of $0.7 million and $2.2 million, respectively, from Corvus' equity method investment in Angel Pharmaceuticals and a noncash loss of $2.3 million in the fourth quarter of 2 associated with the change in fair value of the company's warrant liability.

Total stock compensation expense for the 3 months ended December 31, 2025, was $1.6 million compared to $0.8 million for the same period in 2024. As of December 31, 2025, Corvus had cash, cash equivalents and marketable securities totaling $56.8 million compared to $52 million at December 31, 2024. In January, we closed an upsized underwritten public offering that included a premier group of biotech investors and generated net proceeds of $189 million including the net proceeds from this financing, pro forma cash at December 31, '25, was approximately $246 million, extending our cash runway into the second quarter of 2028.

And I will now turn the call over to Richard, who will discuss our clinical progress and elaborate on our strategy and plans.

Thank you, Leiv, and good afternoon, everyone. Thank you for joining us today for our update call. In 2025, we made significant progress advancing the development of sicolitinib, our first-in-class selective ITK inhibitor that is designed to rebalance or reset the immune system. This was highlighted by the presentation of final results from our Phase IIb trial in peripheral T-cell lymphoma in an oral session at the ASH Annual Meeting and the recent announcement of data from Cohort 4 of our Phase I atopic dermatitis trial, which showed that socolitinib could become a leading therapy for atopic dermatitis and potentially other inflammatory diseases.

Shortly after the data announcement, we completed a $200 million financing, reflecting high investor interest in the opportunity for socolitinib and ITK inhibition given our strong data to date, its unique mechanism of action and its broad potential to help patients across multiple areas of medicine.

As a result, we are entering 2026 in a position of strength with ongoing enrollment in our Phase III PTCL trial, our recently initiated Phase II atopic dermatitis trial and the opportunity to expand into mid-stage trials for other important inflammatory diseases such as hidradenitis suppurativa and asthma later this year.

Based on our current plans and anticipated time lines our cash runway extends beyond key data readouts for all of these programs. On today's call, I will recap the highlights from our Cohort 4 data announcement share the latest on our plans to present additional data from the trial at an upcoming medical meeting and provide an update on our Phase II trial.

I will also review our pipeline expansion plans and key upcoming milestones. The results from Cohort 4 and the full Phase I trial showed that socolitinib's emerging clinical profile appears to provide substantial advantages in the treatment landscape for atopic dermatitis. One, it is an oral medication. Two, it has a novel mechanism of action that combines tissue selective and target specific precision with ability to affect multiple inflammatory signaling pathways. Three, it appears safe and effective in a broad range of patients, including those who have received prior systemic therapies and four, it produces durable responses with no disease rebound.

Based on our market research, this profile would be considered a significant advancement for patients with atopic dermatitis. So we are excited that selitinib data further elevates its profile and potential. It shows one of the strongest results at only 8 weeks of therapy and the durability of responses with no disease rebound may provide the opportunity for new approaches to therapy of immune diseases, including the potential for socolitinib to be an intermittent therapy.

Overall, if the current profile continues to be supported by larger clinical trials, we believe socolitinib will be very well positioned to be among the leading options for the treatment of patients with moderate to severe atopic dermatitis.

I will now review key highlights from our recent data announcement. First highlight efficacy. For cohort 4, which was designed as a randomized placebo-controlled trial with drug given over an 8-week treatment period, the mean percent reduction in easy was 72% versus 40% for placebo that was statistically significant at 0.035. 75% of patients, 9 of 12 achieved EASI-75 and and 1 additional patient was an EASI74. 25% of patients achieved easy 90% and 33% achieved IGA 0 or 1. 11 of 12 patients achieved EASI-50 and the only nonresponder was a patient who was refractory to previous therapy with both DUPIXENT and RINVOQ.

Two of the EASI-90 patients were resistant or nonresponsive to prior systemic therapies. 20% of placebo patients achieved EASI75 and or 17% if you include 2 patients that missed the day 56 evaluation and on later evaluation, never reached EASI75. In addition, 2 placebos required rescue medication due to disease flares versus none in the active group. The two placebo patients who were EASI-75 were both patients who had not received prior systemic therapies, none of 7 placebo patients who received prior systemic therapy achieved EASI75 whereas 3 of 5 active patients who received prior systemic therapies achieved EASI75.

The cohort 4 results confirm our hypothesis from cohorts 1 through 3, which is that extending the treatment duration would deepen responses. The data also show that socalinib is superior to placebo in every efficacy end point evaluated. And when compared to other agents, we believe the results of the team so far for socolitinib place it among the most active agents, oral or injectable approved or under development for atopic dermatitis.

Second highlight, durability.Starting with Cohort 3, we took a more systematic approach to measuring the remission duration with a longer blinded post-treatment follow-up period of 90 days compared to 30 days tracked for cohorts 1 and 2. The cohort 3 data show that responses observed at day 28, the last day of treatment, were maintained or slightly improved out to 118 days or 90 days without therapy. This compares to other systemic therapies for atopic dermatitis, which all show a rapid rebound in disease that starts as soon as 1 week after stopping therapy.

We see no rebound phenomenon with socolitinib, both in cohorts 3 and 4. We believe that the induction of T regulatory cells by socolitinib could be responsible for this durable suppression of inflammation and sustained disease remission. We have seen this in preclinical experiments and biomarker data shows an increase in circulating T regs in cohort 3 patients.

The demonstration of circulating T regs is quite remarkable. As usually, these cells are very rarely found in the blood. It is likely that these cells are migrating to and concentrating in sites of disease, as we have found in our animal models. Third highlight, broad applicability. 35% of all patients enrolled in the Phase I trial had received prior systemic therapies including 50% of patients in cohort 4. Dupilumab was the most commonly used prior therapy followed by JAK inhibitors and some patients received multiple prior therapies. This includes patients who were resistant to their last systemic therapy.

In other words, they were nonresponsive to their prior treatment. Typically, patients that are treatment-resistant or who have gone through multiple prior therapies are more challenging, and this was confirmed when looking at the placebo patients in the trial. The response curve data showed that placebo patients who received prior systemic therapies do worse than those who did not receive prior therapies, indicating that prior systemic therapy is an unfavorable characteristic.

However, the response curves for patients receiving socolitinib are very similar across these groups, indicating that socolitinib is not affected by prior systemic therapy experience. Together with our baseline patient characteristics, this also indicates that the patient population treated on our protocol was more unfavorable than those reported in most atopic dermatitis clinical trials.

As noted above, in patients who received prior systemic therapies, the EASI-75 was 0% for placebo, 0 out of 7 versus 60% 3 of 5 seen in patients who received socolitinib.

So in terms of patient indications, our conclusions are that socolitinib is active in patients who have received prior systemic therapies with outcomes no different than naive patients, despite these patients having more unfavorable disease. Responses were observed in patients who are refractory to their prior systemic therapy. This supports our hypothesis regarding the novel mechanism of action for soculininib and the lack of resistance due to prior therapy experience.

Fourth highlight safety. No new safety signals were seen in cohort 4 with a longer 8-week treatment duration. In cohort 4 and the full Phase I trial reported adverse events are similar in both placebo and active groups. No significant lab abnormalities were observed. There were no hepatic abnormalities, no changes in liver function tests infections were similar and treated and placebos and were minor.

I'd like to make some additional comments on infection. We have received questions from investors regarding the potential for EDV viral reactivation. These questions are based on very rare reports in the literature of EBV infection in babies born with germline mutations in ITK. In a neonate, the immune system is primitive as T and B cells have not yet formed Immune system maturation occurs during development and exposure to antigens.

A germline mutation in ITK in the primitive developing immune system is completely different than transiently blocking the kinase domain of ITK with a small molecule drug in an individual with a mature immune system. We have seen no serious infections of any kind in more than 150 patients treated with soculitinib across our lymphoma, atopic dermatitis and ALPS trials to date. This involves over 14,000 patient days of treatment with some patients on therapy for more than 2 years. In PTCL, -- most patients harbor EBV and other viruses, such as CMD.

In our Phase I lymphoma study we identified over 30 patients with EBV virus detectable at baseline that is before therapy in their blood, measured using a PCR technique that is they are Virena. None of these patients or any other patient had any evidence of EBV reactivation or related illness during the treatment, which in some cases, lasted over 2 years. And recall, these patients are extremely immunocompromised. One other thing to note, ITK inhibition spares Th1 cells, also known as Th1 skewing. T cells are the cells responsible for eliminating viruses.

Now beyond clinical results, biomarkers have been identified that the support the novel mechanism of action with ITK inhibition that leads to immune rebalancing. Some of these biomarkers represent new discoveries. Briefly, the data showed a decrease in IL-4, IL-5 and IL-17 cytokines, a small reduction in tar, a reduction in TH2 cells and an increase in T regs. In ongoing work, we are also finding very significant and interesting changes in Jackpot signaling pathways that will be reported on later. With the additional information that is emerging both from the clinic and our biomarker analysis, such as induction of Tregs, we believe that socolitinib's novel mechanism of action and safety will allow for its utility in diverse indications in immune inflammatory diseases and in cancers.

Our socolitinib abstract was accepted for oral presentation at the Society for Investigative Dermatology or SID Annual Meeting, which takes place in mid-May. We plan to present the Phase I clinical data, expanding our safety and durability data. We will also focus on our biomarker results in this presentation, which we believe will provide novel ideas regarding control of immune diseases.

Our late-breaker abstract was not selected for presentation at AAD, which typically favors later-stage trials. Angel Pharmaceuticals, our partner in China, is enrolling their Phase Ib/II trial in atopic dermatitis. This is a blinded, placebo-controlled trial that is evaluating a 12-week treatment regimen in 48 patients. With socolitinib doses of 100 milligrams BID, 200 milligrams QD, 200 milligrams BID and 400 milligrams QD.

The patient's eligibility and endpoints are the same as was used by Corvus. Depending on the results from the Phase I portion, an additional 60 to 90 patients will be enrolled in the Phase II portion of the study. This trial is open at leading centers in China that are very experienced in performing these types of trials.

The study is conducted in close collaboration with the Corvus team. Results from the initial cohorts are expected late this year.

Now I would like to discuss our Phase II randomized placebo-controlled trial in atopic dermatitis. We announced today that the trial has been initiated. This trial is planned to enroll 200 patients with moderate-to-severe disease randomized into 1 of 4 cohorts with 50 patients in each cohort. We will allow patients who have received prior systemic therapies. -- doses of 200 milligrams QD, 200 milligrams BID and 400 milligrams QD will be examined along with placebo.

The treatment duration is 12 weeks with an off-treatment follow-up period of 90 days. The primary endpoint is median percent reduction in the easy at 12 weeks, a typical endpoint for Phase II studies in atopic dermatitis. Other endpoints include EASI75, EASI90, IGA, PP-NRS and others. This will be an international study. We anticipate the data from this trial will be available in mid-2027. Outside of atopic dermatitis, we continue to enroll patients in our Phase III registration PTCL trial with an interim analysis expected later this year.

We recently conducted a planned meeting of our outside independent data safety monitoring board, no safety signals were observed and the study continues as planned. In December, at the American Society of Hematology or ASH Annual Meeting, we presented the final data from our Phase IIb clinical trial, evaluating sicolitinib in patients with T-cell lymphoma. The data are supportive of the ongoing Phase III program, showing that patients in the 200-milligram BID cohort the same dose being studied in Phase III had a median progression-free survival of 6.2 months and a median overall survival of 28 months comparing very favorably to results with other therapies.

For example, median survivals with chemotherapy are less than 1 year and PFS are less than 3.5 months. The data presented at ASH also shows soculitinib's immunobiological effects and its mechanism of action of affecting T cell differentiation via ITK inhibition. These data support its potential in atopic dermatitis and a much broader range of immune and inflammatory diseases.

We also continue to collect very exciting data from our ALPS or autoimmune lymphoproliferative syndrome clinical trial with 3 patients now on therapy for close to a year. We continue to collaborate with the team at NIAID and our current plan is to submit data for a potential presentation on the study at the ASH meeting in December. In terms of upcoming clinical trials, we plan to initiate a Phase II trial of socolitinib for hidradenitis suprateva and asthma later this year. There are strong scientific rationale for evaluating sicolitinib in HS, which is it is an IL-17 driven disease.

In both in vitro and in vivo animal models, so is a potent inhibitor of Th17 cells and reduces IL-17 production. Our trial designed for HS is further along -- at a high level, we are planning to enroll about 60 total patients with moderate to severe HS into 3 arms: 200-milligram BID, 400-milligram QD and placebo. The treatment period will be 12 weeks and the primary endpoints are safety and efficacy measured by high score 50, high score 75. The asthma study design is emerging and will likely involve about 150 patients treated for 3 months.

In closing, our confidence continues to grow in the long-term potential for socolitinib in atopic dermatitis, peripheral T-cell lymphoma and a broad range of additional inflammatory diseases. We are only beginning to unlock the full potential of ITK inhibition and immunomodulation, which could lead to new and better therapies for inflammatory autoimmune and fibrotic diseases and cancers.

We are building strong momentum with sicolitinib and our ITK platform, and we look forward to updating you on our progress throughout the year. I will now turn the call over to the operator for questions-and-answer period. Operator?

[Operator Instructions]

First question comes from Roger Song from Jefferies.

Great. Congrats for all the progress you have made Richard, maybe just 1 question related to the retro from the data readout you will have before the Phase II, the global come the United States mid next year. So you will have a PTCL potentially data and then also the China 12-week study data. So how should we think about the retro from those data results to the Phase II AD maybe from the efficacy and then the safety perspective, particularly on the high dose, 400-milligram QD?

Okay. So we are anticipating that Angel Pharmaceuticals who is conducting a placebo randomized trial looking at different doses, we'll have some data from their initial couple of cohorts later this year. That would be the first data readout. That's going to be looking at 100 milligrams BID and 200 milligrams QD. But recall, they're going for 12 weeks. They're treating for 12 weeks. We've only gone up to 8 weeks. So that will be very important information for us.

Then at a indentation can report that -- and then the next part of the study will look at a 200-milligram BID and 400 QD, that will be probably middle of 2027, okay? So we'll get some data on more patients and things. Now in total, after that, Angel goes on and does 50, 60 -- or 60 to 90 patients in a Phase II study rolls right into that. In total, you're looking at around 140 patients or so and that yes, 130, 140 patients. And that's totally completed by mid-2027 or early '27.

So we'll have some data from them late this year more data in first half of 2027. The PTCL trial will have an interim formal review in later this year that has a futility analysis as part of it and safety analysis but the complete results are expected in late '27.

Okay. Now what I talked about on the call, was we do have also periodic safety outside independent safety reviews on the Phase III PTCL trial. We had those very recently and everything looked good as I mentioned.

And your next question comes from Li Watsek from Cantor.

Two from us. is first on the data that you're going to present the meeting in May, Richard talked about biomarker and durability data before. Can you just maybe set expectations for us?

Yes. Well, I can set expectations. The durability continues to look great. And in terms of biomarkers, the things I've mentioned previously, but we have discovered some new biomarkers, which is going to be probably the main part of the SID presentation. Fascinating work around the T regulatory cells and some of the JAK-STAT signaling. And the key message there is that you're affecting different multiple cytokine pathways. -- even though you're targeting a very specific enzyme restricted to T cells that can affect several different cytokines, all of which are important in inflammatory diseases, like IL-5 and 4 17, et cetera.

So plus, we'll update the clinical data with the durability and a few other things.

And then my second question Sorry. And my second question is on the Phase II trial in as -- just wondering what the benchmark that you're looking at, especially relative to the approved agents like.

In the space? Do you think in terms of efficacy, you have to match the biologics?

Well, first of all, we have to find the optimum dose, which we're going to look at a couple of different doses -- but of course, the AD study informs us as well as the T-cell lymphoma study informs us on the HS trial. I would expect efficacy as good or better than what's out there, which is what the corrected His scores are, what, 25% or so.

And your next question comes from Graig Suvannavejh from Mizuho.

Richard, congrats on the great progress we're seeing with socolitinib across multiple indications, I just wanted to maybe touch upon a couple of things. First, just on your next data presentations. You did mention that maybe you did apply for late-breaker abstract to AAD. I think you gave us a reason why perhaps your abstract was not accepted, although I do think that Chimera does have a late breaker. I don't know their data set very well as I don't cover it, and so it's not at the top of or the tip of my tongue but any thoughts on whether it is perhaps they had a bigger database because I do think that the -- so curious if you have any thoughts there.

Well, what gets accepted abstracts that get accepted or even publications that accepted, this is a capricious process. And there are a lot of factors. I don't know why they accept some and not others. I personally am shocked that the Chimera with no placebo and an interesting study for sure. But I don't have an explanation for it. There may not be a good one. I just thought I'd speculate I wouldn't get too worried about that. I mean I've had some really, really good papers get accepted at journals and be rejected at others. It is -- at the end of the day, it's One or 2 guys read some abstracts. I used to do it myself. You get a few hundred to review and you you decide what looks good or whatever.

So I don't know if I'd focus too much on any reasons on that. But we're not very active in AAD. We've never done anything there. We don't have boots to our journals I think that's another factor could be another factor. Not sure. Anyway, SID is a good meeting. If anything, scientifically more rigorous -- it is the meeting for early stage and translational biology and research. So we ended up, I think, in a very good place.

Okay. Great. If I could ask just on the Phase II trial in AD that you did start and congratulations there. I think you mentioned that data would be available in middle of 2027 and just trying to get a sense of in between now and mid-2027, Will there be an opportunity for the company to provide some kind of update, -- just trying to get a sense of news flow from that trial from now until mid-2027.

So that Phase II trial is placebo-controlled, randomized and blinded. No, we will not see that data. until it's completed. And as I mentioned, the ANGEL trial is underway that's also blinded and placebo controlled, but they can look at the data after each cohort, similar to what we did in our Phase I. So there will be a news flow from that in terms of the AD stuff.

Okay. And last question, if I could, just on hidradenitis suppurativa, just given coverage of some other companies that I have. I'm under the view that there are not very good preclinical models -- and just wondering then how how do you handicap success in HS when perhaps there are not very well established or good predictive models in HS.

You are correct. There are no good animal models for HS -- but it's pretty clear in the human studies that IL-17 is very important. TH17 and IL-17 are very important, and in TILE-7are approved to treat it. So I think there's a proof of principle already that if you can block IL-17, it should work. And we block IL-17 among the many other cytokines that we block that has a lot of different inflammatory cells, T cells, neutrophils B cells, for example. And again, I think the advantage of socolitinib is that since you're blocking multiple cytokine pathways, you actually affect many lineages, many different lineages.

And I think that's going to be important because when you look at the sites of disease, even atopic dermatitis you just don't see TH2 cells you see a lot of different cells. So I think that that's 1 -- I mean, I would say the best explanation for that is, hey, anti-IL17 works in that disease and we block it even better.

And your next question comes from Jeff Jones from Oppenheimer.

Since I think we've tested maybe talk about AD and how you guys are -- this is a different disease and indication than the dermatological ones, -- how are you thinking about dosing and your strategy there?

I think you mean asthma probably. Yes. You mentioned they did. So well, as you know, atopic dermatitis and asthma frequently go together and drugs that work in 1 often work in the other. They seem to be part of the atopic syndromes. We have several -- now that's 1 where we do have several animal models and our drug works really well in those asthma models, 4 or 5 different models or socolitinib works beautifully.

In terms of , I think it's the same dosing that we've talked about. The AD and PTCL studies inform the asthma. The asthma study is pretty much the same dosing regimens. There will be no reason to change that.

Sorry, just to elaborate. Remember, we have the best biomarker in the world, which is that, and we've been doing this for years. You can give the drug -- you take out the T cells from the patient either in the blood or the sites of disease, and you can measure quite accurately the drug sitting in the target. It is a clean quantitative assay -- it blocks the function of that enzyme. That's a biomarker. And we know that when you give a 200-milligram dose, you pretty much completely block that.

I appreciate that, Richard. And then on the ALPS trial, which you're doing with the NIH, can you maybe comment on how that -- the outcome of that might impact how you think about other indications or inform what you guys are doing?

So ALPS is a disease where you have such an overreactive autoimmune response to so many different things. They have antibodies to red cells and white cells and platelets. And and other things. And in ARP and lymphocyte proliferation abnormal emphasis. And we have seen really interesting results in our patients. So I think the -- that what we're learning there is similar to what we learned in lymphoma is that the drug is very active. It's safe and it's interfering with the signaling pathways that we would predict.

Now I'm not sure I can say, okay, if it works in, it's going to work in lupus, even though the ALPS mouse equivalent is a model for SLE. But I don't think we're thinking of it that way. We're thinking of it as a indicator that we're affecting aberrant auto inflammatory responses in a disease where there's no good treatments really. So it's kind of a model, if you will, but it's a human model. It is an orphan disease. There's no good therapies. -- could you get approval for ALPS? Yes, you could. It's more of a childhood disease. We've been treating adults.

We do intend to increase the number of sites, and we do intend to move down and age into children over the next year or so. We've been talking about that with NIH. So it's another indication, and it happens to be an autoimmune disease.

And your next question comes from Aydin Huseynov from Ladenburg.

Congratulations for the tremendous progress so far this quarter in your pipeline in the drug saclitinib. I got a couple of questions. So first, I wanted to ask about the near term focus near-term Phase II readout interim analysis from the trial in PTCL. I was curious to hear any comments you may provide regarding the enrollment process so far, what types of PTCL, you're actually enrolling? Is it NOS, -- cutaneous -- and what the physicians are using a standard of prefer buildout or pralatrexate. Just curious to your overall dynamic of the trial?

Okay. So let's take that question first. So the trial is enrolling and it's going perfectly according to plan. The patients get randomized into either socolitinib monotherapy 200 milligrams BID versus the investigator's choice of either belinostat or pralatrexate. Now recall, belinostat and pralatrexate are received conditional approval, accelerated approval maybe 15 years ago or so based on response rate in patients with relapsed PTCL.

So in our discussions with FDA, that was the logical control arm. So socolitinib versus those agents. Now it's not a blinded trial because you can't -- well, first of all, we don't usually do that in cancer, but you can't blind socolitiums oral, right, as we know. -- belinostat and pralotrexate are given intravenously and have associated usual toxicities of chemotherapy, mucositis, blood count problems, things like that. So far, the trial is enrolling. We had our first safety monitoring board, and there were no new safety or different safety signals with regard to sicolitinib. -- obviously, is much safer than chemotherapy. So we win on every -- and every count on that.

Now later now the types of patients that are enrolled are, as stated in the protocol, our PTCL NOS, that's the most common one. We do allow anaplastic lymphomas that are out positive. The other big category would be what's called T follicular helper which used to be let's called I angioimmunoblastic lymphoma. So not CTCL. CTCL really is a little bit more of a chronic disease and is treated differently. So that's the reason not to include that in this trial. But it's pretty typical. These are the most common peripheral T-cell lymphomas.

Now peripheral T cell lymphoma, again, just to remind people, there is no fully approved treatment for relapsed disease. It has a median PFS belinostat median PFS is 1.7 months. Prolotrex it is 3 months. And OSes are under a year. So those are really bad -- these are really bad disease. These are sick patients. I can tell you that we are very, very happy with the way the trial is going -- and I think it could represent a very important breakthrough in hematology. -- if we finish the trial and get the results that we're expecting. Does that answer your question?

So appreciate that. Yes. Have another us, if you don't mind? So yes, so regarding the upcoming trial design in asthma, do you plan to have a cohort with patients who may have both asthma and atopic dermatitis. And in your opinion, is there any accelerated path with small pivotal trial with patients with 2 diseases simultaneously. So essentially, that would allow socolitinib secured 2 diseases at the same time. And as we know, Topix is the only drug that treats both diseases, but maybe you can have it in one shot.

Well, that would be great. But I don't know. So first of all, trying to get 2 indications on -- that's really very difficult. And you can get anecdotal information. I know some people report that. And we've had some anecdotal information about that.

But the problem is you don't know how many patients are going to have both diseases concomitantly how severe it is, what measurements you're going to use and how you power the study statistically for each disease. So it's really hard to do that.

Anecdotally, it's something you would look at you have to do a separate trial and even DUPIXENT was separate trials for asthma and eosinophilic esophagitis and COPD and all those things. So it requires a separate trial. Now one thing we are considering is we're really very interested in, I would say, two things. One is this durability of response is quite interesting. And we think we have explanation for it. I think we have very good immunologic explanation for it. It's very elegant and compatible with what's known about the immune responses and so forth.

We also are very struck by the activity we see in patients who failed previous therapies. And I talked about that in my discussion here. So we are allowing, and I don't know if I mentioned it, we are allowing patients who have failed prior therapies in our Phase II atopic dermatitis study. Now some people, many investors have been asking me, why don't you do a separate study in the resistant patients with atopic dermatitis. And that is something we are thinking about. -- that could be a smaller trial because the efficacy and the placebo so the efficacy in placebo -- sorry, placebos do so poorly, you would presumably show a bigger difference with a fewer number of patients.

But we are including both naive and experienced patients in our Phase II. I would do that in Phase III as well which would enable you to get the total population of patients. But there's no doubt that with more and more therapies coming out in atopic dermatitis, the proportion of patients that are not treatment naive. That is that have failed the prior therapies. That pool of patients is increasing. And the pool of patients that is naive is going to decrease proportionately.

Okay. So that the resistant patient becomes, I think, very attractive. So the -- I would say the 2 exciting -- I mean we have a lot of things that we're excited about it's oral and it's safe and and all that other stuff. But the durability is, I think, a game changer changes how you approach the disease. And I think the fact that you can think about frontline therapy or relapsed disease or multiple therapies, intermittent therapy. That's our -- it's the way we think about it.

Makes sense. Very helpful, and congrats with the results.

And your last question comes from Sean Lee from H.C. Wainright.

To touch upon the durability a bit more. I think in the previous Phase I study, you guys follow the patients for up to 3 months -- how long are you following these patients in Phase II? And is the study powering any way to really make a differentiation on the durability of this response.

So the Phase II trial has built in continued blinding of the trial out to 90 days beyond the therapy. So it's 12 weeks of therapy plus the 90 follow-up. That's baked into the protocol. However, the endpoint is the EASI score compared to placebo at 12 weeks. And that's the typical end point to do something different would be sort of typical. What -- now I think that in the future, this issue of how durable the responses are is something that you might study separately.

But I think it stands to reason. I mean, we'll talk more about this, but we have over 90% of our patients don't relapse and follow-up now out to 3 months beyond the last dose. Over 90% of patients disease just doesn't come back. Now you look at other agents do be stat 6, that whatever the -- what's the IL-13s, IL-2s, whatever, these diseases come back pretty quickly in my view, that's not a very good therapy. Best therapy is a shorter treatment duration disease goes away, you don't need to take your drug again for a long time, if at all, hopefully, -- that's asking a lot.

So the durability is important because it's important to understand why it's happening does it pertain to other inflammatory diseases. In other words, how broad is that going to be? Is that unique to atopic dermatitis? Or is that something that you could think about for other autoimmune diseases? And that's why we're excited about that. But anyway, the answer to your question is in the Phase II, it is part of the formal follow-up is blinded, but it's not part of the statistical end point -- the statistical endpoint is the typical one, which is easy score at 12 weeks.

Okay. Got it. For the -- touching on the Atmos second question, is the upcoming study, will you be focusing on our asthma with the cast high? Or are you targeting the more difficult-to-treat T17 driven population as well?

We're probably going to -- so those are some of the things we're discussing now. We're leaning to taking everybody I see -- and for the on. I'm actually -- Sean, I'm glad you brought that up because there's something -- some people will say, well, we only treat TH2 disease. I don't know where that comes from. Some people say, "Oh, you're only selecting patients with atopic dermatitis that are TH2.

First of all, I don't even know how to do that, but we're not doing that. Our atopic dermatitis patients are run of the miltations from U.S. centers. They have to have the necessary eligibility criteria, but we didn't enrich for any patient population. Most of our, by the way, AD patients do not have eosinophilia. Their used initial accounts are normal or low. So I don't think we're going to restrict it to the high EO asthma. Although I have to say the asthma study protocol has not yet been finalized and that's still under discussion.

Okay. Well, first of all, thank you, everyone, for participating in our call. We look forward to updating you throughout the rest of the year and beyond. I appreciate everybody's interest. Thank you.

Ladies and gentlemen, this does conclude your conference call for today. We thank you very much for your participation, and you may now disconnect. Have a great day.

Good morning, everyone. Thank you for standing by, and welcome to the Corvus Pharmaceuticals Conference Call. [Operator Instructions] It is now my pleasure to turn the call over to Zack Kubow of Real Chemistry. Please go ahead, sir.

Thank you, operator, and good morning, everyone. Thanks for joining us today on the call. This conference call is being webcast with presentation slides. We encourage participants to join the webcast in order to view the slides. You can find the link to join the webcast on the Investor Relations homepage of the Corvus website. On the call today are Dr. Richard Miller, Chief Executive Officer; Leiv Lea, Chief Financial Officer; Jeff Arcara, Chief Business Officer; Dr. Ben Jones, Senior Vice President, Pharmaceutical Development; and Dr. Suresh Mahabhashyam, Vice President, Clinical Development.

The executive team will open the call with some prepared remarks, followed by a question-and-answer period. I would like to remind everyone that comments made by management today and answers to questions will include forward-looking statements. Forward-looking statements are based on estimates and assumptions as of today and are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied by those statements, including the risks and uncertainties described in Corvus's quarterly report on Form 10-Q for the quarter ended September 30, 2025, and other filings the company makes with the SEC from time to time. The company undertakes no obligation to publicly update or revise any forward-looking statements, except as required by law.

With that, I'd like to turn the call over to Richard Miller.

Thank you, and good morning, everyone. We are very eager today to present the results from our Phase I clinical trial with soquelitinib in atopic dermatitis. The data reinforced that soquelitinib is a first-in-class oral drug that represents a potential significant breakthrough for the treatment of atopic dermatitis and other immune diseases. I had the privilege of being involved in the discovery and development of 2 pioneering medicines: Rituxan, an anti-CD20 antibody widely used for the treatment of lymphomas and immune diseases; and ibrutinib, a BTK inhibitor also widely used for the treatment of lymphomas and more recently, expanding indications into immune diseases.

It is my belief that selective inhibition of ITK may be following a parallel path and also may now find its place along with these breakthroughs in medicine. Today, I would like to start with some background on ITK and soquelitinib, and then we will cover our safety and efficacy data from all the cohorts and placebo. We will focus mostly on new data from our cohort 4 as well as longer follow-up from cohort 3 and our emerging biomarker data. We will review our data in patients who received prior systemic therapies.

And we will discuss our go-forward plans, including the opportunity for soquelitinib to address a range of clinical indications. Before getting into more details on the background and clinical data, let me summarize the key takeaways as shown on this slide. Cohort 4 results show that soquelitinib could become a leading therapy for atopic dermatitis, and it is oral. First, it confirmed positive clinical results in the trial. It appears that soquelitinib is safe and effective therapy for atopic dermatitis.

EASI 75, EASI 90, and IGA 0/1 were achieved 75%, 25% and 33% of patients, respectively. The mean percent reduction in the EASI score is 72% at 8 weeks of treatment. Second, we have shown deeper durable responses. Extending the treatment to 8 weeks from 4 weeks in cohort 4 is safe and leads to a deepening of response. Third, responses are durable and with continued reduction of EASI scores post treatment, including for longer follow-up in cohort 3. Fourth, soquelitinib is an active drug in patients who have received prior systemic therapies with similar efficacy in systemic treatment naïve or experienced patients.

And fifth, biomarkers have been identified that support the novel mechanism of action with ITK inhibition that leads to an immune system rebalancing. With the additional information that is emerging both from the clinic and our biomarker analysis, such as induction of Tregs, we believe that soquelitinib's novel mechanism and safety will allow for its utility in diverse indications in immune inflammatory diseases and in cancer. Let's get started with the next slide. ITK, or interleukin-2 inducible T-cell kinase plays a crucial role in the differentiation of naïve helper T cells into more specialized cells known as Th1, Th2 and Th17. Gene knockout experiments in mice done many years ago show that knocking out ITK results in the inability to form Th2 and Th17 cells.

These pro-inflammatory cells produce many inflammatory cytokines such as IL-4, 5, 13, 17 and others. So blockade of these cells inhibits production of a range of inflammatory cytokines. Th1 cells possess a redundant enzyme known as RLK or resting lymphocyte kinase. So ITK inhibition does not interfere with their function. The Th1 cell is crucial for antitumor immunity and fighting infection, especially from viruses. This suggests that selective ITK inhibition would not lead to immunosuppression.

More recently, another critical function of ITK was discovered as shown on this slide. ITK controls a switch between Th17 and suppressive T regulatory cells. Independent investigators have shown that using either gene knockout of ITK or blockade of ITK using soquelitinib results in a switch from Th17 to the Treg cells. This is an exciting result as the induction of Tregs has been a highly desired treatment strategy for control of autoimmune diseases. We will be talking more about Tregs later.

Our strategy was to make a drug that would inhibit ITK selectively. If that was possible, then one could potentially reduce inflammation and autoimmunity without causing immunosuppression. This would require a drug that was very specific for ITK and especially spares RLK. The realization of this critical feature and the synthesis of such a pharmaceutically acceptable compound had never been accomplished before.

Based on our experience with BTK and kinase inhibitors, we were able to do just that. This slide shows the exquisite specificity of soquelitinib for ITK as shown on the kinase dendrograms. Here, we compare to ibrutinib, which binds several tech family-related kinases, including ITK. Soquelitinib is an oral covalent irreversible drug that only binds to ITK. The specificity of binding and the dissociation constants are shown in the table. A low number means strong binding. Soquelitinib binds ITK at low nanomolar concentrations.

The details of this work were published last year in the Nature Partner Journal Drug Discovery. Now a word about specificity since it has important clinical implications. In the case of ITK and soquelitinib, we have a target that has limited tissue distribution, T cells and NK cells. And we have a drug that is very specific for that target. The confluence of limited tissue distribution and specificity of the drug portend for safety since potential off-target effects are minimized. So these 2 attributes contribute to the therapeutic index of soquelitinib, number one, the drug-specific binding; number two, the target's limited tissue distribution.

We first initiated clinical development of soquelitinib in T cell lymphoma. In December, we reported final results of our Phase I/Ib study in an oral presentation at the Annual Meeting of the American Society of Hematology, and we are currently enrolling a registration Phase III trial in relapsed peripheral T-cell lymphoma. The evaluation of soquelitinib for T-cell lymphoma has the following rationale: Completely unmet need for better therapies, ability to move quickly into the clinic to obtain safety, efficacy, PK and effects on normal immune cells and function.

Foundation for work in immune diseases since T-cell lymphomas involve Th2 lymphocytes and also commonly involve the skin. The disease is often associated with autoimmune manifestations. An example is shown on this slide. Here are 2 patients from our Phase I T cell lymphoma trial with cutaneous involvement. These patients had massive disease burdens that responded one complete remission and partial remission to monotherapy soquelitinib and they continued on treatment for 2 years, the maximum duration allowed under the protocol.

As we were advancing in the clinic in lymphoma, we were also evaluating the potential for soquelitinib in a range of immune diseases. Briefly, we found robust activity with the drug in many preclinical models, including asthma, pulmonary fibrosis, psoriasis, atopic dermatitis, inflammatory bowel disease and others. An overview of these data are shown on this slide and involve areas of dermatology, pulmonology, rheumatology and gastroenterology. Moreover, in experiments looking at soquelitinib in human cells, both in vitro and in vivo from our lymphoma patients, we confirm the immunologic effects.

As shown here, we found that soquelitinib inhibits the production of IL-4, IL-5, IL-13 from normal T cells, but not interferon gamma because that is a Th1 cytokine. Similarly, looking at malignant Sézary or Th2 tumor cells on the right, we also see reductions of these cytokines, including TARC. On the bottom of the slide, we show studies conducted on the blood from one of the lymphoma patients. These studies show the expected in vivo changes in Th1, Th17 and Th2. Note the profound reduction in IL-5 and eosinophils in this treated lymphoma patient.

With this background, we initiated clinical trials in atopic dermatitis for several reasons. First, it is primarily a Th2 disease, but also involves Th17 and other cell types. Second, it involves the skin, similar to T cell lymphomas. Third, it is a significant commercial opportunity with a need for safe and more effective oral therapies. This slide summarizes the market opportunity. Briefly, there are over 3 million patients with moderate to severe disease and currently only a fraction are receiving therapy. Current therapies are mainly injectables, require continuous therapy and/or have troubling side effects. JAK inhibitors carry a black box warning.

Let's move into our clinical trial in atopic dermatitis or AD. This slide shows the clinical trial design. Patients with moderate to severe AD were eligible if they had failed at least one prior topical or systemic therapy. They were not required to have responded to the prior systemic therapy. This is in contrast to most other clinical trials where these unfavorable patients are not eligible. There were 4 cohorts evaluated sequentially. The study was placebo-controlled and blinded. Placebo controls are critically important in AD studies, especially with novel agents.

The patient and doctor were unaware of the treatment assignment. The company was not blinded. For cohorts 1 to 3, 16 patients in each cohort were randomized to receive active or placebo at a 3:1 ratio, 12 active and 4 placebo. The treatment duration was 28 days with an additional 30-day follow-up off of therapy. Concomitant topical steroids were not permitted. The cohorts evaluated doses of 100 milligram BID, 200 milligram QD and 200 milligram BID. The doses were selected based on our experience in lymphomas where 200 milligram dose was found to produce maximum target occupancy.

200 milligrams BID is the dose being tested in our Phase III lymphoma trial. BID dosing was evaluated because we have shown that ITK protein turnover has a half-life of about 12 hours. Although soquelitinib has a plasma half-life of a few hours, its pharmacodynamic effect is much longer because it is irreversibly bound to the target. We plan to evaluate other once-per-day dosing regimens in future trials since it is not likely that one needs complete target occupancy continuously.

As we discussed a few months ago, based on the promising findings from the initial 3 cohorts, we amended our protocol and designed a new cohort 4 that had some key differences from cohort 1 to 3. Cohort 4 was a prospectively defined clinical trial intended to corroborate and extend the results from cohort 1 to 3. The key differences were: one, 24 patients enrolled using a 1:1 randomization of active versus placebo; and number two, the treatment period was extended to 8 weeks from 4 weeks with 30-day follow-up post treatment.

Soquelitinib dose was 200 milligrams BID, same dose as cohort 3. The 1:1 randomization was done to further strengthen our conclusions. This is especially important in atopic dermatitis, where efficacy endpoints have some degree of subjectivity. The entire study was conducted in the United States at 17 centers. Here are the baseline patient characteristics for the 4 cohorts. A total of 72 patients were enrolled across all the cohorts, 48 active, 24 placebo. The data for the cohort 4 patients is shown on the right. This cohort is very similar to cohort 3. Age, proportion of African Americans prior systemic therapy and mean baseline EASI are very similar. The arms are well balanced. If anything, placebo is more favorable. 50% of patients in cohort 4 had received prior systemic therapies. Let me review the efficacy data for cohorts 1 to 3 before moving to cohort 4. This data has been presented previously, but it sets the stage for our cohort 4 data. As you can see, we find better efficacy in cohort 3, the 200 milligram BID dose, with mean percent reduction in EASI score of 64.8% compared to placebo of 34.4% at 28 days.

The EASI 75 is 50%, 1 patient was an EASI 90. No placebo achieved EASI 75, which is likely due to the short treatment duration of only 28 days, and our patient population is more unfavorable than most studies reported in the literature. Here are kinetics of response for cohorts 1 to 3. Cohort 3 shows a more rapid and deeper reduction in EASI scores compared to Cohorts 1 and 2. The curves are continuously decreasing at day 28. This suggested to us that longer treatment duration could lead to deepening of response. Also, the responses persisted beyond the 28-day treatment period.

For most other treatments, once treatment is discontinued, one sees a return of disease within a few weeks for many patients. This slide shows new data from Cohort 3, where the remission duration has been more systematically examined by amendments to the protocol, which provided for longer blinded follow-up. Responses were maintained or slightly improved out to 118 days, an additional 3 months without therapy. Our hypothesis was that the induction of T regulatory cells by soquelitinib could be responsible for this remission as we have seen in preclinical experiments.

Indeed, we found an increase in circulating Treg cells in cohort 3 patients, but not in cohort 1, 2 and placebo. These cells are functional Tregs that are FOXP3 positive, CD25-high, CD4 and CD45 positive. It is remarkable to find these cells as they are usually very rare in the blood as they are trafficking to sites of disease. It is likely that these cells would be even more abundant in the involved skin sites of disease as we have seen in animal models. Our conclusion from these results is that we may be inducing Tregs that contribute to durable suppression of inflammation and sustained disease remission.

By comparison, here are published results from abrocitinib, Cibinqo, Pfizer's JAK inhibitor from their Phase IIb study. This study followed patients beyond the 12-week treatment period. Shown here are the response curves at the various doses evaluated. The 2 bottom curves are the approved doses of 100 milligram and 200 milligram QD. Note the rapid rebound in disease that starts as soon as 1 week after stopping therapy, week 13. Other agents, including Dupixent, Rinvoq and some of the recent novel agents have similar findings. We have not seen this phenomenon.

I also want to show some of our data on itch as reported using the PPNRS scale. This is a patient-reported outcome. This slide shows the data for cohort 3 compared to placebo. It does appear that we have a significant effect on itch. We also show the frequency of a 4-point change in the PPNRS scale. These are changes that are considered to be very clinically meaningful by regulatory authorities. Since high PPNRS was not an eligibility criteria, not all patients could reach the 4-point threshold. Cohort 4 data is not yet available.

Overall, our conclusions from cohort 1 to 3 were that soquelitinib appears to be safe and effective compared to placebo with a 28-day treatment regimen and disease remissions are durable. Now let's look at cohort 4 results on Slide 19. Here is the 8-week efficacy data for cohort 4. The mean percent reduction in EASI is 72% versus 40% for placebo. This was our predefined endpoint. The p-value is 0.035. 75% of patients achieved EASI 75, 25% EASI 90 and 33% IGA 0/1. 11 of the 12 treated patients achieved EASI 50, 92%. Two placebo patients achieved EASI 75.

On this slide, we show EASI 75 for placebo of 2 of 10 or 20%. Two additional placebo patients were noncompliant and missed the day 56 evaluation and on later evaluations never achieved EASI 75, which would make the proportion 2 out of 12 or 17%. Two placebos required rescue medications due to disease flares versus none in the active group. Our conclusion from these data are that soquelitinib is superior to placebo in every efficacy endpoint evaluated. Here are the response curves for the cohort 4.

This is very clear data with the separation of the curves seen at the first clinic visit day 15 and continuous separation from placebo at day 28, which further increases out to day 56 without a plateau and a steady downward slope. As noted earlier, the day 56 p-value 0.035. We see a continuation in disease control in the post-treatment 30-day follow-up period out to day 86. These data confirm our hypothesis from cohorts 1 to 3, which is that extending the treatment duration would deepen responses. We allowed patients who had received prior systemic therapies in our study.

Our hypothesis was that resistance mechanisms to other therapies would not affect the activity of soquelitinib. This slide shows the prior systemic therapy experience in cohorts 1 through 4 of our trial. 35% of all patients had prior therapies, as shown on this slide, 50% in cohort 4. Not surprisingly, Dupixent was the most commonly used agent followed by JAK inhibitors. Some patients received multiple prior therapies. Some patients were resistant to their last systemic therapy that is not responsive to treatment. Now let's look at our outcomes in patients with prior systemic therapies.

On the left side of this slide, we show the response curves for all soquelitinib treated patients and all placebos cohorts 1 through 4. The efficacy results in all treated patients is strong with a p-value of 0.003 at day 28, which includes all the patients in the study. On the right, we show the response curves for those patients with prior systemic therapy. The separation of curves is very clear in both cases. The curves are very similar for patients receiving soquelitinib, indicating that soquelitinib is not affected by prior systemic therapy experience.

Note that placebo patients who received prior therapies do worse, indicating that prior systemic therapy is an unfavorable characteristic. This results in even greater separation of the curve in -- from the soquelitinib arm. In the next slide, we show a similar analysis for patients in cohort 3 and 4 since they both received the same 200 milligram BID dose. On the left, all patients treated at the 200 milligram BID dose. On the right, those patients who received prior therapies. We utilize the same placebo groups as noted earlier for comparison. we see clear separation of the curves with wider separation in the patients with prior therapy.

Again, the soquelitinib curves are nearly identical, indicating that the treatment effect is maintained in both treatment-naïve and experienced patients. On the next slide, here are all the curves together on 1 plot for cohort 3 and 4, just to highlight that the soquelitinib curves are nearly identical for both prior treatment naïve or experienced. Although not shown, the same is true for the curves with all the patient's cohort 1 to 4. Turning back to the patients that were resistant to their last systemic therapy. We were able to establish confirmation of treatment resistance in at least 6 patients who were not responding to their prior therapy as they came on our study. These patients would be excluded from most clinical trials, which either excludes patients with prior systemic therapy or requires patients to be responsive to that therapy.

All of our patients were in cohorts 3 and 4 and included 4 active and 2 placebo patients. As shown on this slide, the 2 placebos had disease flares requiring rescue medications and 3 of the 4 soquelitinib-treated patients improved with 2 achieving EASI 90s, 1 patient had a 27% reduction. 1 patient did not respond to soquelitinib. This, by the way, was the only patient out of the 12 that did not achieve an EASI 50. Our conclusions are that soquelitinib is active in patients who have received prior systemic therapies with outcomes no different than naïve patients despite these patients having more unfavorable disease.

Responses are observed in patients who are refractory to their prior systemic therapy. This supports our hypothesis regarding the novel mechanism for soquelitinib and the lack of resistance due to prior therapy experience. Here is a summary of the efficacy data for all 4 cohorts looking at EASI 75, EASI 90 and IGA 0/1. Cohort 4 confirms and extends the efficacy of cohort 3 with larger sample size and 1:1 randomization. 75% of soquelitinib-treated patients achieved EASI 75, 25% achieved EASI 90 and 33% are IGA 0/1.

I should note, one additional patient was an EASI 74, a near miss. Two placebos achieved EASI 75. No placebo achieved EASI 90. It is worth noting that the 2 placebos that achieved EASI 75 were both subjects with no prior systemic therapy. None of 7 placebos with prior therapy experience achieved EASI 75 compared to an EASI 75 seen in 3 of 5 actives who received prior therapy. Now let's turn to safety on the next 2 slides. No new safety signals were seen in cohort 4 with a longer 8-week treatment duration. Reported AEs are similar in both placebo and active groups. No significant lab abnormalities were observed.

On the next slide, we show AEs of special interest. There are no hepatic abnormalities, no changes in liver function tests. Infections were similar in treated and placebo. We do not have the problems of conjunctivitis or injection site reactions, which are not only troublesome to patients, but also confound trial blinding. With a novel mechanism of action of soquelitinib, we expect it to identify new and different biomarkers, and we are beginning to uncover these properties.

A detailed description of these is beyond the scope of today's discussion, but we intend to present some of these data at the upcoming American Academy of Dermatology and Society of Investigative Dermatology meetings over the coming months. For now, this slide shows the effects on Th2s and serum cytokines. On the left, we show serum IL-4 levels from cohorts 1 through 4 and placebo. IL-4 levels dropped in cohort 3 and 4, and this drop occurs relatively late. The reduction is sustained and continues beyond the end of therapy in both cohorts 3 and 4, consistent with our findings of prolonged efficacy.

The reduction is dramatic out to day 86 for cohort 4. Next, we show serum IL-5 for cohorts 1 to 3. Cohort 4 results are in process. Each dot is a patient where serum IL-5 levels at baseline and on treatment are measured. Cohort 3 patients have the most reduction in IL-5 levels compared to cohorts 1 and 2, and these changes are seen as early as day 8. IL-5 in placebo patients is not affected. Interleukin-5 is a cytokine primarily produced by T cells and ILC2 cells, innate lymphoid cells. That is crucial for the growth, differentiation, activation and survival of eosinophils.

IL-5 plays a key role in allergic inflammation, particularly in asthma. IL-5 binds to its receptor and signals through STAT1, STAT3 and STAT5. Our findings indicate that changes in serum IL-5 levels occur early relative to IL-4, which occurs later. Next, we show the effects on Th2 cells. In 6 patients analyzed so far using single-cell RNA-seq in cohorts 1 and 2, we see a strong trend indicating a reduction in Th2 cells compared to baseline. This was found in 5 of 6 treated patients with soquelitinib and not in any placebos examined so far.

We are building on this and carefully analyzing cell types and gene expression in cohorts 3 and 4 using single-cell RNA-seq. On the right side of this slide, we show early findings looking at serum IL-17 and TARC, which are both reduced compared to placebo. IL-17 is of particular interest to us since it is a product of Th17 cells, it is involved in atopic dermatitis and it signals through STAT3. We are finding many other indicators supporting our mechanism of action, including effects on JAK/STAT signaling involving JAK1, JAK2, TYK2, STAT1, STAT3 and STAT6. All of this is suggesting that soquelitinib will affect multiple cytokines and cellular functions involved in inflammation.

We have just submitted an abstract on these results for the SID meeting, which occurs in May. Now let's compare our results to other agents. Here, we show the endpoints of EASI 75 and IGA 0/1 for approved biologics and a JAK inhibitor along with soquelitinib. As you can see from this slide, our data at 4 and 8 weeks for cohorts 3 and 4 are competitive with other approved agents at 16 weeks, including JAK inhibitors. We have a sicker patient population. We believe the results obtained so far for soquelitinib place it among the most active agents, oral or injectable approved or under development for AD.

Now I would like to discuss our upcoming plans. With the data shown today, we are very well poised to initiate our Phase II randomized, placebo-controlled trial in AD as shown on this slide. The trial is planned to enroll 200 patients with moderate to severe disease randomized into 1 of 4 cohorts with 50 patients in each cohort. Doses of 200 milligrams QD, 200 milligrams BID and 400 milligrams QD will be examined along with placebo.

The treatment duration is 12 weeks with an off-treatment follow-up period. The primary endpoint is median reduction in EASI at 12 weeks, a typical endpoint for Phase II studies in AD. This will be an international study. We plan to open this trial very soon in Q1 2026. On this slide, we compare the effects of soquelitinib to other approved agents. Soquelitinib affects multiple cytokines and cell types, including IL-4, IL-5, IL-17, IL-31 and many others. It also affects Tregs and ILC2s. This is very different than the mechanisms described for other agents.

Given these properties, the therapeutic opportunities in the I&I space are very broad, and they include Th2-mediated diseases, Th17-mediated diseases, IL-5-driven or allergic diseases and fibrotic diseases.

Recently, in collaboration with Dr. Yannick Allanore at Inserm in Paris, we published an article on the activity of soquelitinib in mouse models of pulmonary fibrosis, including a transgenic model of systemic sclerosis. This paper has just appeared in the journal Arthritis Research & Therapy. The next slide summarizes the large and growing market opportunity in the I&I space. As you can see from the slide, the market is anticipated to grow to $170 billion by 2030 with oral agents expected to gain an increasing proportion, which is still only a small fraction with the potential for significant growth.

Let me summarize our findings to date and go-forward plans. Soquelitinib is first-in-class selective ITK inhibitor with a novel mechanism of action that appears well suited to address a broad range of immune diseases, including atopic dermatitis. Clinical data in atopic dermatitis now confirms that soquelitinib appears to be safe oral medicine that produces deep responses that are durable with relatively short treatment periods, including in patients who have received prior systemic therapies.

It blocks multiple critical immune cell signaling pathways that reduce inflammatory cytokines and rebalance cellular immune function through effects on Tregs and other cells. Looking forward, we have multiple value creation opportunities for soquelitinib. Phase II clinical trials in AD, hidradenitis suppurativa and asthma are planned to start in 2026. A Phase III registration trial is ongoing in relapsed peripheral T-cell lymphoma.

Finally, we have a strong intellectual property position on soquelitinib. The composition of matter patents have issued in major territories, providing protection through 2042. Other patent applications covering methods of use monitoring, et cetera, have been filed. Since we invented soquelitinib, there are no royalty or other financial obligations related to the IP of this drug. In closing, we are very excited about our IT program as we believe it will have broad applications across many areas of medicine.

On a personal note, I consider soquelitinib to potentially be a revolutionary approach to the treatment of immune diseases. I am very proud to work alongside our talented and dedicated employees and collaborators as we bring this important new therapy to patients. Thank you. Operator, I think we can now open the call for Q&A.

[Operator Instructions] Your first question comes from Roger Song with Jefferies.

Great. Huge congrats for the data. It's coming a long way. A couple of questions on the data per se. First of all, the two missing patients missing on the 8-week visit, you mentioned they are non-compliant. And I'm just curious about what else they are non-compliant, why we should not care about those 2 patients? And then if you can just let us know the EV reduction for those 2 patients at a later time point after 8 weeks.

Thank you for the question, Roger. The 2 missing placebos of the data is included up until day 56. In other words, they came in, in all the visits, including day 43. So that data is included in the curves. They missed day 56, they come in, let's say, a week or 2 later. They're not counted in any subsequent data. We just carry that through. Now of those patients, the EASI scores were -- I know one was an EASI 50 and one was not an EASI 50. The exact numbers are -- one was a minus 17 at a later visit, and that is 17% reduction, one was about a 60% reduction. If you included those 2 patients, if we took those time points and put them in the response curves, the p-value, it doesn't change the curves hardly at all. You can even see the difference. The p-value instead of being 0.035 is 0.038. Okay. And then I forgot the rest of your question.

No, this is great. And then regarding the H-score, I understand you have a pretty profound number on the cohort 3. The cohort 4 data is not available yet. So -- but can you let us know what is the baseline age for the cohort 4? And then can you comment on the directional reduction on the H-score for cohort 4, I think?

Okay. So first of all, the cohort 3 data, the baseline was about 6.5 to 7, if you look at the curve I showed. In cohort 4, 7.2. That's the average, I guess, 7.2. Yes. So we did not require a baseline itch score, PP-NRS score of a certain level, which we are going to be requiring in our Phase II trial. And obviously, if you don't -- if you have a low PP-NRS, then it's difficult to show the 4-point change. So in our future trials, we will require at least 4 or more. So I know others talk about percent change in itch. That's really not a very good way to look at it. It is a patient-reported score. It's highly variable. We did not really rigorously collect it in our Phase I because we were more interested in safety and objective efficacy parameters.

In our Phase II, it will be done more rigorously with electronic capture or reporting and very uniform requirements for when the patient does it. It's influenced by a lot of things, what time of the day the patient reports the score, where they are, how happy they are, things like that. So it's an important endpoint, but it has to be captured very rigorously. In any event, we see a very nice change in itch at -- in our cohort 3. And I think you can see from the biomarker data that cohort 3 and 4 seem to be producing more effects.

Last question from us. In your Phase II design, you decided to include the 400 milligram QD as one of the dose cohort. Just curious about the risk of the war, given you haven't tested that dose cohort as QD, but you also mentioned the durable PD effect. Do you need that QD to be -- to make [indiscernible] to be very commercially viable?

Well, first of all, I think QD dosing is going to be possible, in fact, likely with our drug because it does have a sustained effect. It's a covalent irreversibly bound drug. We also see that in a lot of different laboratory work. The 3 doses that are being evaluated in the Phase II, 2 of them are once a day, 200 milligrams once a day, 200 milligrams twice a day and 400 once a day. Now the 400 milligram once-a-day dose is actually being tested in China by our partner, Angel Pharmaceuticals. So we will have data on that.

Your next question comes from Aydin Huseynov with Ladenburg.

Congratulations with this essentially JAK-like efficacy. I got a couple of questions for you. So given the mechanism of action for soquelitinib and this efficacy that you reported, do you think it would make sense in the future to position the drug as a first-line therapy ahead of JAK inhibitors and ahead of Dupixent?

I think that soquelitinib could be a first-line treatment for atopic dermatitis or later line. It's -- I think that our clinical trial and our planned Phase II clinical trial, where we will also enroll experience prior systemic therapy patients will position us to be a drug that would be used frontline or later line. Of course, as these other agents are out there, more and more patients are becoming treatment experienced. So I think the beauty of our drug is that we have a drug now where we're showing that it doesn't matter whether you use a first line or later line.

And so I think we -- I think that whole -- that entire indication is open for us. Now what I -- do I think dermatologists would prefer to use our frontline, our agent frontline? Well, I think it's safe. It's convenient. I also think that we don't have the rebound phenomenon that all these other treatments have. I mean that's pretty clear already. So I think that there's no reason not to use our drug frontline.

I'm trying to understand the EASI curves for soquelitinib and when they may potentially plateau. So I'm looking at Rinvoq EASI curves. I think they plateau at week 8 and Dupixent curves plateau at 12. So for soquelitinib, so it still seems to be pretty steep at week 8. So given the mechanism of action, the ITK inhibition, when do you think theoretically, the curve can plateau what would 12 weeks trail, 16, 24? Just curious to hear your thoughts on this.

Well, you can't go below 100. So it's going to plateau somewhere. But it does look like there's a straight downward slope continuing as you point out. And that's one of the reasons we're going to 12 weeks in our Phase II. I mean it's going to plateau out somewhat. I mean I'd be careful cross-trial comparisons are always dangerous and especially dangerous in AD and especially now where you have a lot of other treatments out there now. So trying to compare us to a Dupixent curve from years ago in a naïve population is difficult.

I think you can see from our demographics that we have 35% of our patients had a prior therapy. You can see and that makes a difference in the disease as shown by our placebos. Now we also only have 24 subjects in cohort 4. It's a good trial, 1:1 randomization, well balanced, but it's only 24 subjects. So I don't know where it's going to plateau, but we're going to test it beyond the 8 weeks. Now I do think that we're moving into a paradigm shift in how we may treat this disease. If we're talking about resetting immunity, then -- and not just blocking a factor, not just blocking a cytokine, but resetting the immune system, then we're in an era now where you can talk maybe about intermittent therapy. where you would treat for some period of time and just watch patients and disease comes back, retreat them.

And I've been through that before. That's the Rituxan story in lymphoma, where intermittent therapy became a way to manage low-grade lymphoma for years, for years. And I personally have had patients I took care of with Rituxan where they had intermittent therapy over 20 years. That's how old I am. And I think that's a good strategy. I don't -- I think the current therapies for AD where you take a drug for months and months and you stop and the disease comes back in a few months, that's not very satisfying. Patients don't like diseases to come back that soon. They don't like the diseases at all. And they don't like to take drugs forever either, whether they're oral or injectable. So I think that -- I think with our mechanism of action, which is coming into focus now, I think we have an opportunity to establish new paradigms in therapy.

And given the lasting Tregs and actually Rituxab being used across all 3 lines of therapies. So I have another question for hidradenitis suppurativa. So given the efficacy that you've shown in atopic dermatitis, atopic dermatitis is obviously established market, more than $10 billion. Hidradenitis suppurativa is not established yet, but it could be potentially larger. But curious to hear your thoughts on how soquelitinib may position itself in hidradenitis suppurativa and actually, across all these 3 large derm indications, atopic dermatitis, hidradenitis suppurativa and psoriasis, where do you think soquelitinib may show the largest differentiation versus standard of care, especially IL-17?

So first of all, the reason we're going -- one of the reasons we're going after HS or hidradenitis suppurativa is because it's primarily a Th17 disease. Atopic dermatitis is primarily Th2, although Th2, Th17 are involved in all of them. So there is a strong scientific rationale to go after HS, and that's the reason. We have an oral drug. I forget the name of the drug from UCB, the antibody that requires injections. So again, I think that if we show similar efficacy in HS, you have the same argument, why not use it frontline? I mean it seems to be safe, and it seems to -- if it turns out to be effective in that disease in our Phase I study in that illness, I don't see why it wouldn't become frontline.

And by the way, psoriasis, psoriasis makes a lot of sense for us. We just didn't go into that because it's such a competitive space. Now as we get more experience, perhaps we will go into that space. Psoriasis from a scientific rationale is a beautiful disease for us. Th17, other inflammatory components makes a lot of sense for us. And mechanistically, the story behind our ITK inhibitor is getting really interesting and really exciting.

And I think we're going to have a good story about that at the SID meeting. I mean some very interesting things are happening to gene expression for these inflammatory cytokines and the STAT -- JAK/STAT system. Remember, IL-17 signals through STAT3, IL-5, STAT1, STAT3, STAT5. So we affect several of those, which gives us the opportunity to be much broader in terms of our potential indications.

Congrats again over this great data.

Your next question comes from Li Watsek with Cantor.

Congrats on the home run data. Maybe just one on maybe longer-term safety. And I guess just based on what you've seen so far, including some of the data points from PTCL dataset. Can you just talk a little bit about your confidence on the clean safety profile is going to continue to hold up over time?

Okay. Thank you for that question. Regarding safety, we have a lot of experience with safety now. And you pointed out, thank you for reminding me about the lymphoma study. We have hundreds of patients now treated with soquelitinib out over months and years. And in the lymphoma study, these are very fragile, usually elderly patients with multisystem problems, tumor infiltration in many organs, liver, kidney, et cetera, lung. We have not seen a single patient, not a single patient in our lymphoma study has discontinued therapy due to a safety or toxicity reason.

We have not seen any liver function test abnormalities. We've not seen any hematologic suppression. Now I know some of our tables at meetings so hematologic abnormalities. But in our lymphoma patients, many of our patients come on. They're already anemic, they're already neutropenic, et cetera. So those are not drug related. And so far, in our 72 to 48 patients with atopic dermatitis, we really don't see any safety signals. In fact, I think our AE rate is lower than placebo, which is -- well, which is amazing. So we also are not surprised by the safety.

We really saw no dose-limiting toxicities in animals. We saw no dose-limiting toxicities in our Phase I lymphoma study where we end up to 600 milligrams BID. There was no signs of any toxicity, even though we were super saturating the target. So we have no animal tox issues that we've seen. We didn't see it in patients. And again, I said it earlier in my presentation, there are 2 reasons for this, very, very specific drug, very specific drug and a target that is very limited.

I mean, go look at the Human Protein Atlas of ITK, you'll only find it in some lymphoid tissues. That's where your T cells and NK cells are. Go look at some of these other targets that people look at. They're all over the place. So my experience with Rituxan, one of the reasons Rituxan was so good and so safe is that same thing. If you look at where CD20 is expressed, very limited, only in lymphoid tissues where there's B cells. So specificity and selectivity usually go towards safety because you don't have the off-target problems.

And maybe a strategy question. As you think about the development path for soquelitinib as this drug can potentially go very broad. You talked about asthma HD and can be a pipeline in a drug. So that would require a lot of resources. So what are your thoughts on going along versus bringing someone on board at some point?

Well, we're certainly open to -- first of all, we understand that we can't study all these diseases and all these disciplines ourselves. And we are engaged in discussions with various potential partners, and we're going to explore opportunities that make sense for us. So we're certainly open to that.

Your next question comes from Graig Suvannavejh with Mizuho.

Congrats on the data. I've got 2 to start with. One, can we just revisit the data and the remarkable efficacy results, but in the context of what seems to be a very clean placebo response where you're not seeing anything from EASI scores. Could you just remind us kind of how you think about what you saw from the placebo group, what might explain very low EASI scores there?

And then also as we go and look forward to the initiation of your Phase II study and it being a longer study, what might you think about that placebo-adjusted efficacy? So that's kind of my first question. And my second question, just if you could just remind us of the competitive landscape in terms of the ITK inhibitor players and how your molecule might differentiate from others that may be in development?

So all right, let's talk about placebos. First of all, we have a placebo. That's the first point. And placebos are very important in these kinds of trials because, as I mentioned, there is some degree of subjectivity, and there's a strong psychological component. I don't understand it, but patients once they start taking these pills, even placebos, they feel better and they even respond -- seem to respond to them. So placebos are very important. Now in our cohorts 1-3, and I know some people have brought this up to me, we had 0 placebos reach EASI 75. And look, first of all, it was a relatively small sample size. It was only, what, 24 patients or something placebo. So it's a small sample size, number one.

Number two, it was only 28 days of therapy. So you have a short window and the chance of a placebo dipping into the EASI 75 is reduced. And thirdly, and I think this is more significant, I'm absolutely convinced that the patient population in cohorts 1, 2 and 3 and 4 for Corvus are sicker much sicker than what's been reported in prior literature, especially if you start going back and looking at papers 10 years ago, where there was no other therapy these guys were getting.

So I think that the cohorts 1 to 3, 0 was a reflection of sicker patient population, short therapeutic window and small numbers. We did more patient's, we probably would have seen some placebos. Now in cohort 4, we did increase the number of placebos. We had 2 patients who achieved EASI 75. And that would be 20% or 17%, depending on how you want to count it. That's within the range of most studies. So I don't think there's anything abnormal there. Now again, I did mention that of those 2 placebos, they did not receive prior therapy. Of 7 placebos that did receive prior therapy, 0 achieved EASI 75, 0. We start to see the difference there and how that matters. And whereas we did see EASI 75s, in fact, EASI 90s in some of our active patients. So what do we have? 75% reached EASI 75 versus, call it, 20%. That's a good result. It confirms our cohorts 1 to 3. It puts us in, I think, the efficacy realm of JAK inhibitors, although we don't have, obviously, the treatment experience. But it looks like we have JAK-like activity, better safety and no rebound, which is, I think, a big point.

So our placebos overall, if you look at our -- put it all together, our placebo rate is very similar to what other studies are. Maybe it's a little lower, but I would explain that based on sicker patients. Now the second question was ITK landscape. So first of all, we've been pioneers in this space. We have -- I should say, we've benefited from lots of great immunologists who did work 20 years ago and over the last several years on this. So we benefit from their great work. But in terms of the clinic and human biology, we've been the pioneers. And we -- the inventive step for us was to be absolutely rigid in our requirement for specificity for ITK.

And a lot of other people, once ibrutinib was successful, everybody started making kinase inhibitors to that family of targets, but they didn't really spend or think much about specificity. But we actually knew from the studies that were published 20 years ago that gene knockout studies that specificity was important, and it turns out to be true. I think now we've confirmed that. So I don't know of any specific ITK inhibitor in clinical trials at the moment. But I think after today's call, you can count on a lot of people working on ITK inhibitors. Now they know it needs to be specific. And every one of them, let's see what, 3 months from now will say they're better than we are. But we can count on that.

Now we're not standing still either. We have a very active program of second, third-generation compounds. Looking at other nuances of ITK biology that I don't need to get into here. We have some nice degraders that we've made that we're sorting through. So we think that the ITK target is a platform. ITK turns out to be a really, really important target in T cells involved in T cell receptor signaling, involved in differentiation, involved in apoptosis, involved in a lot of other things. So at the moment, we're the leader, although I expect there to be intense competition. Did I answer your question, Graig?

You did.

Your next question comes from Etzer Darout with Barclays.

Congrats on this dataset. Just curious about feedback from clinicians on the soquelitinib profile. Just trying to get a sense of how they may view this data, particularly in patients with prior systemic therapies and in the backdrop of competitive landscape. And then secondly, if you could comment on what you view as sort of potential timing of the Angel Pharma dataset and whether or not that's something that could be incorporated into your Phase II design. I understand that they only started that in the fourth quarter of last year, but just curious if there's anything you could kind of learn from that trial ahead of starting your Phase II?

With regard to physician excitement about our drug, I think the physician feedback has been extremely positive. Obviously, the fact that we're oral, the fact that we don't have the safety signal. And I have to tell you, some of these docs who had refractory patients and they start taking soquelitinib and then respond, even though it's blinded, they figure out that it must be active, they can't be placebo. So it's been very positive. And of course, the mechanism of action is actually beautiful. The specificity of the drug and the mechanism of the action is quite interesting and impressive. Now regarding Angel, I don't think I should comment on that. They just started their trial. There will be data coming out of that later this year.

Your next question comes from Jeff Jones with Oppenheimer.

And just to echo congrats on the really strong dataset. I guess one question around the placebo patients in the mean EASI reduction. At the end of therapy, it looked like clearly, the soquelitinib patients didn't sort of have a rebound effect, but it was interesting that it looked like the placebo patients seem to hold on there as well to their response. Any thoughts on what you're seeing there?

Small sample size and also a couple of placebos flared. And so you can't follow that. So that, I think, is the explanation for that. And Jeff, one other thing, when you have a small reduction in EASI, it becomes easier or harder to -- I get what am I looking for? It's harder to show a change. I mean, if you're going to rebound and -- I mean, if you only reduce a small amount and you go up a little bit, it's not that significant. It's easier to see changes -- it's easier to see rebound when you have a big effect, on other words. So if you look at that graph I showed of abrocitinib, when you look at the lower doses on placebo, they hardly have any rebound because they didn't respond very well to begin with.

Appreciate that. And then I guess, end of last quarter, you reported around $66 million with runway into 4Q of this year. Can you comment as to whether the studies that you're planning in AD, asthma and HS are included in that runway or not?

Let me turn that over to Leiv.

Jeff, those studies are included. But I should say we know we need to raise more capital. That's pretty clear, and we'll raise more capital when appropriate.

Sorry, we have another question. Let's take one more question, operator.

Your next question comes from Sean Lee with H.C. Wainwright.

Congrats on the great data. I just have 2 quick questions. First, for the upcoming Phase II study, are there any significant differences in the inclusion and exclusion criteria for the patients compared to the Phase I?

The answer to that is no. We will allow prior systemic therapy, but we're capping that at 40%. The only reason to cap it is because if we left it open, you'd get 100% prior therapy. And we want to make sure that the -- that we keep our indication broad. But basically, no difference in the eligibility.

And my second question is, could you provide a quick highlight of the clinical milestones expected this year and their timings?

So we expect an interim analysis from our lymphoma study later this year. That's a futility analysis. We expect to start asthma. We expect to start HS. They won't read out until next year, '27. The Phase II AD study will take 18 months approximately to read out. Am I forgetting anything? Those would be our milestones.

I think that concludes the Q&A for now. First of all, I want to thank everyone for participating in our call. We're really excited about the future for soquelitinib and ITK inhibitors and our pipeline. Thank you all, and we look forward to updating you on future calls. Bye.

Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.

Good afternoon, everyone, and thank you for standing by, and welcome to the Corvus Pharmaceuticals Third Quarter 2025 Business Update and Financial Results Conference Call. [Operator Instructions]

It is now my pleasure to turn the call over to Zack Kubow of Real Chemistry. Please go ahead, sir.

Thank you, operator, and good afternoon, everyone. Thanks for joining us for the Corvus Pharmaceuticals Third Quarter 2025 Business Update and Financial Results Conference Call.

On the call to discuss the results and business updates are Richard Miller, Chief Executive Officer; Leiv Lea, Chief Financial Officer; Jeff Arcara, Chief Business Officer; and Ben Jones, Senior Vice President of Regulatory and Pharmaceutical Sciences. The executive team will open the call with some prepared remarks, followed by a question-and-answer period.

I would like to remind everyone that comments made by management today and answers to questions will include forward-looking statements. Forward-looking statements are based on estimates and assumptions as of today and are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied by those statements, including the risks and uncertainties described in Corvus' quarterly report on Form 10-Q for the quarter ended September 30, 2025 and other filings the company makes with the SEC from time to time. The company undertakes no obligation to publicly update or revise any forward-looking statements, except as required by law.

With that, I'd like to turn the call over to Leiv Lea. Leiv?

Thank you, Zack. I will begin with a brief overview of our third quarter 2025 financials and then turn the call over to Richard for a business update.

Research and development expenses in the third quarter of 2025 totaled $8.5 million, compared to $5.2 million for the same period in 2024. The $3.3 million increase was primarily due to higher clinical trial and manufacturing costs associated with the development of soquelitinib as well as an increase in personnel-related costs.

The net loss for the third quarter of 2025 was $10.2 million, including a noncash loss of $300,000 related to Angel Pharmaceuticals, our partner in China. This compares to a net loss of $40.2 million for the same period in 2024, which included a $32.8 million noncash loss related to the change in fair value of Corvus' warrant liability and a $700,000 noncash loss related to Angel Pharmaceuticals.

Total stock compensation expense for the third quarter of 2025 was $1.2 million, compared to $700,000 in the same period in 2024.

As of September 30, 2025, Corvus had cash, cash equivalents and marketable securities totaling $65.7 million, as compared to $52 million at December 31, 2024. Consistent with our last quarter, we expect our current cash to fund operations into the fourth quarter of 2026.

I will now turn the call over to Richard, who will discuss our clinical progress and elaborate on our strategy and plans.

Thank you, Leiv, and good afternoon, everyone. Thank you for joining us today for our update call.

Our primary focus continues to be on the development of soquelitinib for both atopic dermatitis and T-cell lymphomas, and we have several important milestones upcoming for these programs. First, we have completed enrollment in the extension Cohort 4 of our Phase I trial, and we expect to have the results of the full data set in late December. Given the proximity to the holidays, we plan to report results in January.

Second, the initiation of our Phase II atopic dermatitis trial is on track for early Q1 2026. We believe soquelitinib is strongly positioned as an oral medication with a novel mechanism of action that so far has shown favorable safety and efficacy profile. There has been increasing interest in drugs with novel mechanisms to address atopic dermatitis and other inflammatory diseases. Our confidence in soquelitinib is bolstered by our belief that the data to date not only stands up favorably against recent data sets from other approaches, but indicates that we have the potential to be a leader in this space.

We are also encouraged that the clinical evidence obtained to date with soquelitinib in both atopic dermatitis and in T-cell lymphoma bode well for the potential of ITK inhibition in a broad range of immunology and inflammatory indications, and we continue to explore potential next opportunities for our platform.

On today's call, I will provide an overview of extension Cohort 4 and our plans for reporting this data and the status of our planned Phase II trial in atopic dermatitis. I will also discuss the relevance of our soquelitinib ASH oral presentation for our Phase III peripheral T-cell lymphoma trial and its implications for I&I indications, including atopic dermatitis, and I will provide a brief recap of other operational progress and updates.

Let me start with a reminder of the key data reported to date for soquelitinib in atopic dermatitis. In June, we reported data from Cohort 3 of the Phase I trial evaluating a 200-milligram twice per day oral dose for 28 days of treatment, building on the encouraging results we had already reported with a lower dose level from cohorts 1 and 2. All of the treatment cohorts demonstrated a favorable safety and efficacy profile compared to placebo. The Cohort 3 efficacy data was especially remarkable, demonstrating earlier and deeper responses compared to cohorts 1 and 2.

At day 28, Cohort 3 showed a mean percent reduction of EASI score of 64.8%, compared to 54.6% for the combined cohorts 1 and 2 and 34% for placebo. In Cohort 3, 50% of patients achieved EASI 75, 8% achieved EASI 90 and 25% achieved IGA 0 or 1. No placebo patients achieved EASI 75 or IGA 0/1.

We also saw an impact on itch with a number of Cohort 3 patients reporting steep drops in patient reported PP-NRS score beginning at day 8.

In terms of the kinetics of response, Cohort 3 showed earlier and deeper separation from placebo starting at day 8 compared to cohorts 1 and 2, with the EASI score improvement continuing through day 15 and 28. The continuous downward slope of the curve suggests that longer treatment duration could potentially deepen responses further, which we are now exploring with the extension Cohort 4.

We have completed enrollment in the extension Cohort 4 of the Phase I trial, which is evaluating 24 patients at the Cohort 3 dose of 200 milligrams twice per day given for 8 weeks, with an additional 30-day follow-up without therapy. The 24 patients were randomized in a blinded fashion one-to-one with placebo, 12 active and 12 placebo. As mentioned earlier, we plan to report the 8-week data set on 24 patients in January. Our objective with this additional data is to confirm the results obtained in our earlier cohorts in a larger number of patients and to determine if the longer treatment duration of 8 weeks leads to better efficacy.

The second upcoming milestone for soquelitinib in atopic dermatitis is the initiation of our planned Phase II clinical trial, which we anticipate will begin early Q1 2026. The trial will be randomized, placebo-controlled and double-blinded, involving approximately 70 clinical trial sites globally. The trial was designed to enroll approximately 200 patients with moderate to severe atopic dermatitis that have failed at least 1 prior topical or systemic therapy.

I would like to emphasize that we are including patients who have failed previous systemic therapies such as Dupixent or JAK inhibitors. We are interested in this population of patients because soquelitinib has a mechanism of action that is different than currently available agents, and prior use of these agents would not be expected to lead to resistance to soquelitinib.

The patients will be randomly randomized equally into 4 cohorts, 50 patients each receiving soquelitinib 200 milligrams once per day, 200 milligrams twice per day, 400 milligrams once per day, or placebo. The treatment duration will be 12 weeks, and patients will be followed for an additional 90 days without therapy.

The primary endpoint will be the mean percent reduction in EASI score from baseline to week 12. This is the typical endpoint for Phase II clinical trials in atopic dermatitis. Secondary endpoints will include the percent of patients achieving EASI 75 or IGA 0/1 at week 12, impact on itch measured by the percent of patients achieving greater than or equal to 4-point decrease in PP-NRS at week 12, and safety.

Photographic documentation of disease at baseline and response to therapy will be mandated on the study and reviewed by independent experts.

In oncology, we continue to enroll patients in our registrational Phase III trial of soquelitinib in patients with relapsed PTCL, driving towards interim data in late 2026. In addition, we are pleased to report that the final results from our Phase I/Ib clinical trial of soquelitinib for the treatment of relapsed/refractory T-cell lymphomas will be presented in an oral session at the Annual Meeting of the American Society of Hematology meeting in December.

This presentation will report on the clinical data and supporting preclinical work that drives us to continue advancing the program for PTCL as well as providing the rationale and safety information motivating us to focus on immune and inflammatory diseases. In particular, we will report on the durability of progression-free and overall survival. We believe the presentation at ASH adds to the growing clinical evidence that soquelitinib is a safe and active agent working through a mechanism that supports its utility in both T-cell lymphoma and immune-mediated diseases.

As a reminder, some patients in the Phase I trial were treated beyond 2 years in the same daily dose range as is being studied in atopic dermatitis. And complete durable tumor responses were seen in patients with highly aggressive tumors.

We also have a growing body of preclinical data supporting the potential of ITK inhibition in a broad range of additional indications across dermatology, rheumatology, pulmonary medicine, solid cancers and other diseases.

Briefly on other operational updates. In October, we appointed Mr. David Moore to our Board of Directors, building on the addition of Richard van den Broek in April. David is Executive Vice President, U.S. Operations, at Novo Nordisk and President at Novo Nordisk. His experience leading one of the most successful GLP-1 franchises along with his broad expertise across strategy, commercial, market access, business development and investing is anticipated to be an important strategic resource as we work to maximize the potential of our ITK inhibitor platform.

In closing, we remain very optimistic about the potential of soquelitinib in atopic dermatitis. In addition, the knowledge and experience from our current trial motivates us to think beyond atopic dermatitis, to a broad range of other immune diseases. We believe we may have the opportunity to establish selective blockade of ITK as a new therapeutic approach to autoimmune inflammatory diseases based on modulation or rebalancing of cellular immunity. We look forward to providing soquelitinib updates in the coming months. First, at ASH for our T-cell lymphoma program, and then in January for the extension Cohort 4 data for our atopic dermatitis program.

Combined with the planned initiation of our Phase II atopic dermatitis trial in early Q1 2026 and the ongoing enrollment in our Phase III PTCL trial, we are building significant momentum for soquelitinib coming into the new year.

I will now turn the call over to the operator for questions-and-answer period. Operator?

[Operator Instructions] Your first question comes from the line of Graig Suvannavejh from Mizuho.

Congratulations on the progress in the quarter. I had a couple of questions. First, on your ASH abstract and the data that you will be presenting next month, I'm wondering, we saw very impressive OS data, and with that in mind, with other information that was in that abstract, could you perhaps put in context the comparability that obviously leads to your enthusiasm for the prospects of soquelitinib in peripheral T-cell lymphoma? And I'll come back with a second question.

First of all, the PFS and OS being presented at ASH meeting is quite impressive, the -- especially when you consider this is a Phase I trial using an agent that was not previously tested in this disease. As you all know, T-cell lymphoma is a very bad disease with a median survival usually of about 6 months in relapse. We have far better results than that, and we're excited about that.

The reason that we're also excited is we've learned so much from that trial in terms of immunobiology, safety, pharmacokinetics, pharmacodynamics, mechanisms of action that pertain to -- that are very pertinent with regard to immune diseases. One of the things I talk about in the ASH abstract, and we'll elaborate on at the meeting, is the fact that we're seeing responses in T-cell lymphomas that are so-called GATA3-positive. Now GATA3 is a transcription factor that is also known as the master regulator of Th2 function. Th2 cells are the cells of interest in a variety of immune diseases, including atopic dermatitis.

So putting all that information together we feel bodes well, not just for the T-cell lymphoma program, but for a range of immune diseases. It's confirming and consistent with our belief that we have a drug with a really new novel mechanism of action, it's oral, it appears very safe. And we are seeing really significant signals of activity in patients who have a cancer of their immune system that involves the very same cells that are involved in all these other immune diseases. I hope I answered that question with...

You did. And then if I could just go to soquelitinib and your atopic dermatitis readout that's coming in the early part of the year, as you have expanded the treatment duration and as you've expanded the number of patients, is it fair for us to assume that what you saw previously will have an improvement on the efficacy that you saw? And if you don't see an improvement versus what you saw previously, does that change in any way your enthusiasm for the prospects of soquelitinib in atopic dermatitis?

So first of all, we feel, and so do many of our outside experts feel, that the data that we generated in Cohort 3 with 28 days of treatment was quite good. It was safe and it was quite active in that. What we aim to show -- and as you recall, the reduction in EASI scores were continuing to go down for the last few weeks of therapy.

So with the expanded cohort, we really are looking for 2 things. Number one, we want to show consistency. We want to show confirm what we showed before in a larger set of patients with more placebos and more patients with getting active drug. Placebos, I don't have to tell you folks, placebos are very important in evaluating these diseases.

The second thing we're looking for is: does the extension of the treatment duration improve the results further? So those 2 concepts. I want to see consistency of the data from what we did earlier, and yes, we'd like to see an improvement as we go beyond 28 days. And of course, we want to confirm safety and the other things as well. So that would be what to expect as we look at the data that comes out in January.

Your next question comes from the line of Jeff Jones from Oppenheimer.

Congrats on the real progress you're making here. One on soquelitinib. Richard, as you mentioned, you've seen and been generating data in a number of other indications in the I&I space. What are your plans to take soquelitinib forward in other indications at this point, sort of indications and timing?

Okay. So just to be clear, Jeff, soquelitinib in humans is being studied in the registration Phase III trial and, of course, in our Phase II atopic dermatitis trial. We also have a trial in lymphoproliferative disease called ALPS that you know about. Now we have many preclinical models that we've evaluated soquelitinib, everything from asthma, atopic dermatitis, psoriasis, [ scleroderm systemic ] sclerosis, et cetera. We are making definite plans to move into other immune-related diseases. I'll be talking more about that early next year. The key diseases for us now appear to be asthma and probably another dermatologic condition yet to be defined.

Great. Appreciate that. And then you -- or the Kidney Cancer Research Consortium reported an update on the cifo trial at ESMO. Just curious as to the next steps there. The trial is still ongoing, there are still patients on follow-up. How are you thinking about ciforadenant in the context of renal cell and beyond?

So as you know, the cifo trial was done in collaboration with the Kidney Cancer Consortium, who paid for most of the trial. I don't think we have any other expenses related to that. There were 19 patients still on treatment and on follow-up, 19 out of 50, 40% or so almost. So we're going to continue to follow those people, and we'll decide what to do once we see how the rest of the data evolves. But that's our current plan for that.

Your next question comes from the line of Li Watsek from Cantor.

Congrats on the progress. I have a couple of questions here. First, maybe just in terms of baseline characteristics of the Cohort 4 versus prior 3 cohorts? Is it reasonable for us to assume they're pretty similar to Cohort 3? Or is there any difference that we should keep in mind? And I have a follow-up.

It is very reasonable for you to assume that the characteristics are very similar to Cohort 3. And to elaborate on that, the enrollment in the trial is 17 centers, all U.S. centers, the same centers that were utilized for the first 3 cohorts. None of the criteria for eligibility have been changed. And yes, we know the demographics already of our patients, very, very similar to those Cohort 3.

Okay. Great. And then for the Phase II trial, given the patient population that you'll be enrolling, it sounds like the patients can be exposed to JAK inhibitors and GLP. So just given this demographic, what should be the bar for the EASI score?

Okay. So first of all, when we go to Phase II, of course, it's a larger trial, 200 patients. It would be very difficult, take a long time to enroll that solely in the U.S. So there is going to be a heavy reliance on sites outside United States, particularly in Europe, which is what most companies are doing now.

I think that we're somewhat unique in that we're allowing patients who failed Dupi and JAK and other systemic therapies, within reason, I mean, you can't fail 10 therapies. But now the reason we're doing that is that we have some patients that we've seen in cohorts 1, 2, 3, and now even in the fourth cohort, that have failed those systemic therapies, and they're responding to our drug.

So I don't know what the final numbers are going to be on that yet, whether it's identical to first-line therapies or somewhat not identical. So it's a little bit hard for me to say what the bar is. First of all, I'm not aware of any data that has specifically been published on the response of a drug to somebody who's failed the JAK inhibitor or Dupi. Now those studies do, I know recycle patients, they take patients who are EASI 50s and they treat them again for longer periods of time. But that's really kind of a different kind of experiment.

So look, I think it's a little early to set a bar for the Phase II. Let's get our Phase I results. Let's take a look at the Dupi failures and the JAK failures, and then we can talk more about that. But I think it is an important point. I'm glad you asked the question, that the Corvus patient population is a little bit different. Now we're doing that deliberately. We want these failures because we think that we have a drug with a mechanism of action that is going to -- where the mechanism of resistance to a Dupi or JAK is really -- may not really be pertinent or relevant for our mechanism. And then we need to learn that.

So the good news here is that it expands the potential use of our drug. We feel that it potentially could be used first line or it could be used in the relapsed situation.

Your next question comes from the line of Aydin Huseynov from Ladenburg.

Congrats on the progress this quarter and appreciate taking questions. I got a couple. So Richard, so you're already running a trial in atopic dermatitis, and I was curious to hear any thoughts on potential other dermatologic indications such as either hidradenitis suppurativa, vitiligo or psoriasis or anything else. And can you run several trials simultaneously -- several dermatologic trials simultaneously? I just wanted to get your thoughts on this.

Okay. So the preclinical models and the data we have in the lab tells us that asthma should be a very good indication for us. We also think that a disease like hidradenitis suppurativa would be a very good disease for us. It's in the dermatology space, and that's a disease that's both Th2 and Th17 driven. So let's think about that a little bit.

A Dupixent, for example, or a STAT6 inhibitor or whatever is going to get your Th2-type cytokines, but it's not getting Th17 because that doesn't signal through STAT6. So we think we have a distinct advantage here for a disease like HS because we hit 17 and Th2. There are other reasons as well.

So other diseases we're thinking about are prurigo nodularis, that's a Th2/Th17 disease as well. That's not as common, but there's even more of an unmet need there. Alopecia areata, we've considered. It's a very competitive space. JAK inhibitors work well, but that's still on our list, and we're still doing some work on that.

Now your question, can we run more trials? We intend to run multiple trials in immune disease. We intend to push this drug in multiple areas, as I mentioned on my talk, not just in dermatology, pulmonary medicine, oncology, rheumatology, et cetera, et cetera. Now of course, we know at some point here, we're going to have to raise some money to do that. And we're optimistic that with the data that we have coming out, that we'll be in a position to raise money to fund those activities.

Very helpful. And one more question I have regarding Phase II registration trial. I just wanted to better understand the time lines, potential readout, and hopefully, the potential launch of the drug. So given so many developments with soquelitinib, I guess this is the first indication, that's the first indication where we're going to launch the drug. And I just wanted to get a better sense of immediate commercial opportunity and the time lines in PTCL for soquelitinib.

Yes. So well, our time line is a futility interim analysis at the end of 2026, probably finish full data by end of 2027. Launch would be, I think, relatively quick for this. One of the beauties of this trial is that it's a single registration randomized trial that could lead to full approval should you meet your endpoints. And it's 150 patients, relatively small trial, with relatively short endpoints. The control -- the chemotherapy control arm is expected median PFS, which is the primary endpoint of, what, 3 months, 2 months.

So we're excited about it. I'm an oncologist and lymphoma is my expertise, as you know, and I ran a clinic at Stanford for 25 years or more taking care of lymphoma patients. There is no treatment, no good treatment for this disease. There is no competition at this point. Even in the research stages, I mean, really, there's nothing new in this area. So we think we have the potential should this drug be approved, where it will be used immediately in all T-cell lymphomas: frontline, late line, you name it, because really, there isn't anything else. I mean we have a ways to go before we can figure all that out, but the opportunity here, we think, is much larger than people recognize.

Now it's not atopic dermatitis in terms of the number of patients, of course, but it also doesn't have the competition and it also doesn't have the very long time lines to approval.

Your next question comes from the line of Etzer Darout from Barclays.

This is Jordan Becker on for Etzer Darout. Congrats on the updates. Two questions. You alluded to it, but I just want to double-click on this. Do you plan to do any post-hoc analysis following the [ Cohort 4 ] completion to look at efficacy in Dupi and JAK-naive and refractory populations?

And then two, can we expect a similar analysis in terms of biomarker correlates of clinical efficacy with the updated data?

The answer is yes and yes, Jordan. Thanks for the question. We, of course, will be doing post hoc analysis trying to figure out how the drug is working, how to make it work better, all sorts of things. So clearly, looking at the effects of prior therapy, prior systemic therapies, all those clinical variables will be evaluated. We do have a pretty aggressive biomarker program. We're minimizing biopsies of the lesions on patients only because that does hurt enrollment, and we don't want to do that. But we have a pretty extensive program now looking at single-cell RNA sequencing of blood, and that's revealing a lot of interesting things. I mean there's a lot of new things that are coming out on this.

I think the same old, same old look at IL-13 or whatever, that's going to go [ bye bye, park ], et cetera. Those are not good biomarkers. Everybody knows that. The best biomarkers for these diseases are yet to be defined because they're heterogeneous diseases and we don't really know what the cause is.

So we're looking at a lot of that. We'll report on what we find. The biomarker game is a tough game. There's a lot of variables to look at and hard to make much of anything when you have a small number of patients. But we certainly will hope to get clues and signals that we can validate in larger trials.

Your next question comes from the line of Sean Lee from H.C. Wainwright.

I just have a couple of quick ones on the design of the upcoming Phase II AD study. So what's the reason behind settling on a 12-week duration treatment rather than the 8 weeks that you're testing in the Cohort 4? And are there any notable differences between the enrollment criteria of the Phase II compared to the patients that you're enrolling in Phase I?

So far, the eligibility criteria are pretty much identical. The reason we're going to 12 weeks is we're going to examine that. Most therapies are out at 16 weeks now. But if you look at the data from most studies, you'll see that most of the separation, most of the efficacy is obtained in the first 12 weeks. You don't really gain that much more by treating longer. So that's the reason for our 12-week study.

Look, I'm trying to make this a shorter treatment, not a longer treatment, okay? I don't know any patient, and I've been -- as I mentioned earlier, running a clinic for over 30 years, I don't know any patient who wants more medicine to take longer. So I'm trying to see if we can go shorter. -- not longer. But of course, we want to maximize -- both are important. You want to maximize responses. You want to hopefully shoot for total clearance of disease that is EASI 100%, that's what you want. And that's what we'll try to do.

But that's -- if you look at most studies, you don't gain much by going from 12 weeks to 16 weeks. Now some people are going to 6 months, 1 year. I mean, great. If you're willing to take a drug for that long, for an incremental benefit that's marginal.

Your next question comes from the line of Cha Cha Yang from Jefferies.

This is Cha Cha on for Roger Song. I was hoping that you could give us some color on any of your plans for potential partnerships or licensing deals for soquelitinib in the coming future, or if you plan to raise money and take this forward yourselves in either AD and oncology.

Okay. So thanks for the question, Cha Cha. I can tell you that ITK as a target is on the radar of every major company that works in this area. I know that because we're talking to them. We'll evaluate partnering opportunities as they arise, whether it be in oncology or immune diseases. At this time, however, we're pushing forward with our cancer program and our immunology program.

We, as I mentioned just a few minutes ago, we do recognize that we're going to have to raise more money to maximally develop all these programs. We're optimistic about our data and we think there will be ample opportunity to raise funding, whether it be through offering stock or partnerships at the appropriate time.

Next question is from the line of Graig Suvannavejh from Mizuho.

I was very curious as you think about your ITK portfolio and comments around potentially advancing next-generation ITK, I was wondering, Richard, if you could share kind of the vision or strategy around the potential of adding another indication for soquelitinib versus moving forward with a next-generation ITK inhibitor with perhaps a similar indication in mind. Just how do you balance that kind of strategy.

Well, that's -- thank you for the question. That's a good question. Obviously, pushing forward with soquelitinib, which now has a wealth of safety and efficacy data in hundreds of patients, is -- will move faster than bringing along one of our backup compounds, which, of course, still have to go through IND-enabling studies. And then if you go in the immunology space, don't forget you need to do normal volunteer single-dose, normal volunteer multi-dose. So that takes time.

But we are going to consider all that. Right now, we're pushing forward in the PTCL, atopic dermatitis and soon other immune diseases. We're also considering other dosage forms and formulations of soquelitinib. We're working on that now. We're also looking at soquelitinib-like ITK degraders. We've made some of those. We're looking at those in the laboratory. Interestingly, it turns out that soquelitinib, a covalent drug, leads to degradation of the ITK target to a certain extent. We've learned that. That's really interesting. I don't think anyone has known that before.

So we're looking at any and all of that stuff, but certainly pushing forward with our lead compound, that was going to be the fastest.

Your last question is from the line of Jeff Jones from Oppenheimer.

Just a quick one. Digging a little bit deeper into the Dupi and JAK-exposed patients that could be enrolled in the Phase II study, would you guys be powering the study to really do a subgroup analysis that could be statistically significant again and separate those systemically exposed patients versus systemic therapy naive patients?

No, we would not be doing that. I mean that's -- I mean we don't have enough information yet, Jeff, to make a commitment like that. But one thing for sure, we will stratify the study to look at that subgroup. So what I mean by that is that will be a defined subgroup. We will stratify randomization based on whether you fail this -- a prior systemic therapy or not. You want those equally distributed in your placebo and in your active arm.

But without really knowing the efficacy [ signal that ] we would expect in that it's a little hard to power how many patients you would need and what effect you're looking for. I think that would be going pretty far. I'm not sure you'd want to do that at this stage. I'd rather do a study, include everyone -- the best outcome, do a study, include those people, have a positive study in your predefined endpoint. You get approval, I mean if it were Phase III, you get approval for everyone.

Yes. No, great. And the other way to look at that would be stratifying. So really appreciate the clarity.

As there are no further questions at this time. I would like to turn the call back to Mr. Richard Miller for closing comments. Sir, please go ahead.

Thank you very much, operator. Thank you, everyone, for participating in this call. We look forward to advancing the soquelitinib programs and our other programs. And we look forward to updating you on our progress as we move forward into 2026 and beyond. Thank you very much.

Ladies and gentlemen, this concludes today's conference call. Thank you very much for your participation. You may now disconnect.

Good afternoon, everyone. Thank you for standing by, and welcome to the Corvus Pharmaceuticals Second Quarter 2025 Business Update and Financial Results Conference Call. [Operator Instructions] It is now my pleasure to turn the call over to Zack Kubow of Real Chemistry. Please go ahead, sir.

Thank you, operator, and good afternoon, everyone. Thanks for joining us for the Corvus Pharmaceuticals Second Quarter 2025 Business Update and Financial Results Conference Call. On the call to discuss the results and business updates are Richard Miller, Chief Executive Officer; Leiv Lea, Chief Financial Officer; Jeffrey Arcara, Chief Business Officer; and Ben Jones, Senior Vice President of Regulatory and Pharmaceutical Sciences. The executive team will open the call with some prepared remarks, followed by a question-and-answer period. I would like to remind everyone that comments made by management today and answers to questions will include forward-looking statements.

Forward-looking statements are based on estimates and assumptions as of today and are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied by those statements, including the risks and uncertainties described in Corvus' quarterly report on Form 10-Q for the quarter ended June 30, 2025, and other filings the company makes with the SEC from time to time. The company undertakes no obligation to publicly update or revise any forward-looking statements, except as required by law. With that, I'd like to turn the call over to Leiv Lea. Leiv?

Thank you, Zack. I will begin with a brief overview of our second quarter 2025 financials and then turn the call over to Richard for a business update. Research and development expenses in the second quarter of 2025 totaled $7.9 million compared to $4.1 million for the same period in 2024. The $3.8 million increase was primarily due to higher clinical trial and manufacturing costs associated with the development of soquelitinib as well as an increase in personnel-related costs. The net loss for the second quarter of 2025 was $8 million, including a noncash loss of $400,000 related to Angel Pharmaceuticals, our partner in China. In addition, we recorded a noncash gain of $2 million from the change in the fair value of Corvus' warrant liability during the second quarter of 2025.

This compares to a net loss of $4.3 million for the same period in 2024, which included a $1.8 million noncash gain related to the change in fair value of Corvus' warrant liability and a $600,000 noncash loss related to Angel Pharmaceuticals. Total stock compensation expense for the second quarter 2025 was $1.3 million compared to $800,000 in the same period in 2024. As of June 30, 2025, Corvus had cash, cash equivalents and marketable securities totaling $74.4 million as compared to $52 million at December 31, 2024. During the second quarter, all of the remaining common stock warrants were exercised, resulting in cash proceeds of approximately $35.7 million which included $2 million from warrants exercised by our CEO, Dr. Miller.

Based on our current plans, we expect our current cash to fund operations into the fourth quarter of 2026. I now turn the call over to Richard, who will discuss our clinical progress and elaborate on our strategy and plans.

Thank you, Leiv, and good afternoon, everyone. Thank you for joining us today for our update call. Our main focus continues to be the development of soquelitinib for atopic dermatitis, where we believe we are uniquely positioned with an oral medication featuring a novel mechanism of action that so far has shown favorable safety and efficacy profile. We are making significant progress on multiple fronts, including new data from our Phase I trial reported in June that increases our confidence in the long-term potential for soquelitinib in this indication and beyond. On today's call, I will provide a high-level recap of this data, review our go-forward clinical plans, including our planned Phase II trial design and briefly discuss our progress with our other clinical programs. We view the data through Cohort 3 of the Phase I trial as very encouraging.

All of the treatment cohorts demonstrated a favorable safety and efficacy profile compared to placebo and Cohort 3 data is especially exciting, demonstrating earlier and deeper and more durable responses compared to Cohorts 1 and 2. Specifically, at just 4 weeks of treatment, Cohort 3 showed a mean percent reduction of EASI score of 64.8% compared to 54.6% for the combined Cohorts 1 and 2 and 34.4% for placebo. No placebo patients achieved the clinically meaningful endpoints of EASI-75, EASI-90 or IGA 0 or 1. We compare this to the results seen for the soquelitinib patients where many achieved these endpoints. In Cohort 3, 50% of patients achieved EASI-75, 8% achieved EASI-90, and 25% achieved IGA 0 or 1. This compares to 29%, 4% and 21% in the combined cohorts 1 and 2 that were treated, respectively. In terms of the kinetics of response, Cohort 3 showed earlier and deeper separation from placebo beginning at day 8 with the EASI score improvement continuing through day 15 and 28 and far beyond.

For Cohorts 1 and 2, the separation from placebo began at day 15 and showed continued separation at day 28. For all 3 cohorts, this separation was maintained during the 30-day post-treatment follow-up period. In addition, for all 3 cohorts, the downward slope of the curves at day 15 to day 28 suggests that longer treatment duration could potentially deepen responses further. We also have found a remarkable impact on PP-NRS, a patient self-reported assessment of itch. A number of Cohort 3 patients reported steep drops in the score beginning at day 8, which aligned with the reductions we see in serum cytokine levels of IL-31 and IL-33. Both of these cytokines are known to be involved in the itch response. In addition, other biomarker data from the trial continues to support the ITK inhibition mechanism of action, including the potential induction of anti-inflammatory T regulatory cells.

Regarding safety, there were no safety issues observed with soquelitinib with no significant differences between treatment and placebo groups and no clinically significant laboratory abnormalities were seen. The total current treatment experience with soquelitinib now involves over 150 patients with T-cell lymphoma or atopic dermatitis, representing more than 9,000 patient treatment days. In our lymphoma trial, some patients have been on continuous daily therapy up to 2 years. Based on the results obtained to date, we are advancing the clinical development of soquelitinib in 2 ways. First, we amended the Phase I trial protocol to replace the previously planned Cohort 4 with an extension Cohort 4 that will evaluate an additional 24 patients at the Cohort 3 dose of 200 milligrams twice per day given for 8 weeks with an additional 30-day follow-up without therapy. The 24 patients will be randomized in a blinded fashion 1:1 with placebo, 12 active and 12 placebo.

The extension Cohort 4 will give us data on a longer treatment duration of 8 weeks versus 4 weeks seen with Cohorts 1 and 3. We have now enrolled more than half the patients and continue to anticipate that data from the extension cohort will be available in the fourth quarter. Second, we are finalizing the design of our planned Phase II clinical trial of soquelitinib for atopic dermatitis, and I am happy to share those plans with you now. The trial will be an international randomized, placebo-controlled and double-blinded. The company will also be blinded. It will enroll approximately 200 patients with moderate to severe atopic dermatitis that have failed at least one prior topical or systemic therapy. Patients will be required to have a baseline EASI score that is greater than or equal to 16, IGA of 3 or 4 and body surface involvement that is greater than or equal to 10%.

The patients will be randomized equally into 4 cohorts, 50 patients in each cohort receiving either 200-milligram soquelitinib once per day, 200 milligrams twice per day, 400 milligrams once per day or placebo. Let me repeat those groups, 200 milligrams once per day, 200 milligrams twice per day, 400 milligrams once per day or placebo. The treatment period will be 12 weeks, and patients will be followed for an additional 30 days without therapy. The primary endpoint will be the percent change in EASI score from baseline to week 12. Secondary endpoints will include the percent of patients achieving EASI-75 or IGA 0 or 1 at week 12. The impact on itch will be measured by percent of patients achieving greater than or equal to 4-point decrease in the PP-NRS scale at week 12 and of course, safety as well. We anticipate including 30 to 40 clinical trial sites globally. We are currently finalizing the trial design with the investigators with strong interest from many leading centers, and we are on track to initiate the trial before the end of the year.

Outside of our clinical trials, our partner in China, Angel Pharmaceuticals, plans to initiate a Phase Ib/II trial of soquelitinib for atopic dermatitis in China. This study will enroll 48 patients and is anticipated to build on the data from our Phase I trial by studying a longer treatment period of 12 weeks and an additional dosing option of 400 milligrams once daily, in line with the direction we are headed with our Phase II trial. Briefly on our other clinical programs, we have submitted an abstract to present the final results from our Phase I clinical trial of soquelitinib for the treatment of relapsed/refractory T-cell lymphomas at the American Society of Hematology meeting in December. We continue to enroll patients in our registrational Phase III trial of soquelitinib in patients with relapsed PTCL, driving towards interim data in late 2026.

In addition, patient enrollment is ongoing in our Phase II trial of soquelitinib in patients with ALPS, autoimmune lymphoproliferative syndrome. Depending on enrollment trends, it is possible we could see initial data from the Phase II ALPS study in late 2025 or early 2026. We have completed enrollment in our Phase II trial with ciforadenant in renal cell cancer. These data will be presented in an oral presentation in October at the ESMO meeting, European Society for Medical Oncology. In closing, the soquelitinib results in atopic dermatitis and T-cell lymphoma underscore the importance of ITK as a critical target for a range of diseases involving inflammation and cancer and the broad potential for soquelitinib in many areas of medicine, such as dermatology, oncology, rheumatology, pulmonary medicine and other areas.

We feel we may be entering a new era of immunotherapy for autoimmune inflammatory diseases that is based on drugs with novel mechanisms of action that modulate or rebalance immunity by keeping pro-inflammatory or aberrant T cells in check. This potential has motivated us to complement the development of soquelitinib with the discovery and development of next-generation ITK inhibitors with unique properties. In the near term, we look forward to continuing the clinical development of soquelitinib in atopic dermatitis and PTCL and look forward to providing updates on our programs in the coming quarters. I will now turn the call over to the operator for a questions-and-answer period. Operator?

[Operator Instructions] Your first question comes from Jeff Jones.

Congrats on a hugely productive quarter. I guess you've got a plethora of opportunities in front of you. As you think about Cifo in autoimmune disease, in addition to accelerating as you are in the Phase II, how are you thinking about next indications and financially being able to support the many opportunities that Cifo represents?

Okay. So Jeff, let me first correct. Yes, Cifo is renal cell cancer. But soquelitinib obviously, we're pursuing aggressively atopic dermatitis, but we've already begun to think about follow-up indications. And the 2 indications that we're thinking about, we're thinking about 2 of them. One, of course, would -- we sort of want to maintain our presence in dermatology. We have experience there now. We have a lot of information on, we think, the behavior of the drug in these cutaneous diseases. So I think a likely target for us might be something like hidradenitis suppurativa. There is totally unmet need there, I would say. And then the other disease moving away from dermatology in the inflammation area would be pulmonary disease. Asthma is probably scientifically the most justification for a disease is probably asthma. We have 3 or 4 different animal models where we see excellent activity of our drug in asthma, both acute and chronic.

Also the mechanism of action, specifically the inhibition of what are called innate lymphoid cells really leads us to believe that we might have a very important novel approach to asthma and perhaps other pulmonary diseases. But you're quite right. We -- it is difficult for us to pursue all these indications. But we've shown that we're very adept and agile in terms of efficiently maximizing the value of, I'd say, each of our products.

I appreciate that. And then the follow-up question is actually on Cifo. In terms of the renal update coming at ESMO, how are you thinking about next steps for the program, assuming with [ an oral ] that there's going to be a positive update here on the program?

Okay. So just to remind everyone, ciforadenant is an A2A antagonist, the oral medication. We did a Phase II study in first-line renal cell cancer, patients who are receiving ipi + nivo. So we added the A2A antagonist. And the idea there, of course, is to look at response rate, but also very importantly, to look at since they stay on the A2A antagonist every day for a long time, they get the ipi + nivo for a short time. I think one of the things that we'll be looking for in addition to, of course, objective responses is the durability of responses and PFS in other words. So let's see what that data is. This is a study that was conducted by the Kidney Cancer Consortium, several centers, MD Anderson, Vanderbilt and several others. They ran that study. We, of course, provided the drug and some financial support. So let's see what's presented in an oral presentation at ESMO, and then we'll go from there. Based on the data that comes out of that, we'll make our decisions about how to follow up on that.

Okay. But it is quite a unique study. I mean, it's first-line disease. It's renal cell cancer. We know that's immune-responsive. I'm emphasizing this because I know today some other company came out with some A2A stuff, and I think it was metastatic colon cancer, and they had chemotherapy and a number of various treatments there and one of the things that we've always done well is to carefully study our agents initially as a monotherapy and then move into combinations where we have a good understanding of the efficacy and safety and mechanism. So that's helped us a lot. Does that answer your question?

It does.

The next question comes from Graig Suvannavejh.

This is Sam on for Graig. Congrats on the progress. Maybe just a quick one on soquelitinib and PTCL. Just curious how the enrollment is going and if the previous guidance for data in late 2026 is still there.

Our guidance is still intact. We're enrolling according to plan. We have probably about 20 centers open now. These are the best of the best centers in the United States and Canada. So everything there is going according to plan. And we're hoping that our presentation on the Phase I will really start to focus attention on this drug.

Your next call comes from Aydin Huseynov.

Congrats with the quarter. A couple of questions from us. So could you walk us through the decision process, thinking process regarding the Phase II trial design for atopic dermatitis. So I appreciate giving us color about 4 different cohorts, 200 Q.D., 200 B.I.D., 400 Q.D. and placebo. Just so far, we see in atopic dermatitis, the most productive cohort is Cohort 3. So I was curious to better understand, was it more like an FDA suggestion to give a little bit weaker dose, a little bit harder -- a little bit stronger dose? Just walk us through the process, if you could.

Okay. Thank you for that question. So first of all, there's a lot of precedents now for Phase II trials in atopic dermatitis. We're not the first company to do that. And a 200-patient trial with roughly 50 per arm is, I would say, pretty standard. And you are correct, Aydin. Usually, there is -- the FDA wants to see some dosing -- different doses studied so that you can determine what's the lowest dose that's possibly effective and what's a higher dose that becomes maybe not more effective than another dose. So we selected these doses because the 200 once a day, we think is active. We don't think it's going to be -- and we've already tested it. You've seen that data in Cohort 2. I think that will be an active dose. It's a single -- it's a daily dose. Some people, of course, prefer a single dose, once-a-day dosing for atopic dermatitis. But the 200 B.I.D., we saw a better response. That's a doubling of the dose in our Cohort 3, and that's what we're studying in our extension now. So that's the second cohort, 200 once a day, 200 twice a day.

And then, of course, we want to do 400 once a day, same total dose as the 200 B.I.D., but given once a day. I think we can do once-a-day dosing. So this will give us an opportunity to confirm that. And then, of course, placebo. I can't emphasize enough how important it is to have placebos in Phase I and Phase II trials. I am seeing companies now do these studies with no placebos, and it's absolutely astounding to me. But in any event, so 50 patients in each arm, 200 total, placebo-controlled, totally blinded, company is blinded. The endpoints are pretty standard. The mean percent change in EASI is the usual primary endpoint for a Phase II study, secondary endpoints being EASI-75s and IGA-0 and 1s. So that's all really pretty standard.

Yes, and we're moving to 12 weeks of therapy. We'll have experience with 8 weeks of therapy, which we already have right now. And we think that, that should give us a pretty good result. In terms of the statistics, if we have even a 20% improvement in any of the groups, you can just -- we can just look at any one group versus the placebo. If we're 20%, 22% better, we want to -- we expect to be better than that. But even if that's at the lower end of our -- of our information. We have an 80% power to see that a p-value of 0.05 on that. And in the Phase II trial, that will be fine. So the sizes statistically make sense. The dosing makes sense based on what we know and what we also know about occupancy and the receptor. And we think this is a very manageable trial for us. There's a lot of experience in doing these international Phase IIs, 200 patients would be very manageable for a company like Corvus. I hope that answered your question.

Absolutely. Yes, it does. Just wanted to -- a couple of follow-up questions on this trial. So I know this could be a little bit early, but would you be able to provide the time line, when do you think we can see the results? I mean, I understand this is randomized blinded trial, but if you could give us some hints in terms of when it could be ready.

Okay. No, happy to give that. We've, of course, been thinking about that. I think you're looking at enrollment in 12 to 15 months, maybe you have results in 18 months, and we'll start the trial in December. And we have a couple of things, I think, going for us. Obviously, it's oral. That should help enrollment. I think the second thing, novel mechanism of action, I think that will also facilitate enrollment. We're not requiring biopsies, although we're going to have some centers where we're going to try to motivate people to do some biopsies. But of course, that should also improve enrollment. But the biggest thing that's going to facilitate enrollment is that we are allowing patients who have failed systemic therapies. So that really opens up the potential patient population. So many of these studies, they won't take you if you've already failed a systemic therapy, a JAK inhibitor, let's say, or a dupi or something like that or an anti-IL-13, but we're allowing those patients.

And the reason we're allowing those patients is because our mechanism of action is completely distinct from those, number one. And number two, we've had patients like that on our study so far, and it hasn't mattered -- they've done just as well.

So my assumption is that you'll probably be stratifying based on which exactly therapy they failed topical or systemic but yes.

Absolutely. I mean there are a few things you might stratify on. Obviously, EA -- I mean, if you're baseline EASI score, that will be a stratification factor and whether or not you failed the systemic therapy. Yes. We haven't gotten into that degree of detail yet, but there'll probably be 2 or 3 different stratification factors. You can't get too many in a study with only 200 patients.

Right, right. Yes. And my question I have was about the next-generation ITK inhibitor. As we move forward with that, could you give us some thoughts on how it will be different from soquelitinib and which indications you'd be planning to target if it's not too early?

Okay. So first of all, for certain intellectual property reasons, I'd rather not go into the details of how they're different because there are a lot of people who are now working on ITK inhibitors. And I'd rather not go into the details. But suffice it to say, let me answer your question this way. ITK plays many roles in a cell, T cell receptor signaling, everything from T cell receptor signaling to control of Th2 cytokine production to apoptosis. And we think we have compounds that might work better for some of those indications than others or some of those mechanisms. So let me answer it that way.

There are no further questions at this time. I will now turn the call over to Richard Miller. Please continue.

Thank you, operator. First of all, let me thank everyone for participating in today's call. Look forward to updating you again in the next quarter and updating you on the progress with all our clinical trials. Thank you very much.

Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect.