Richard Miller
Thanks, Leiv, and good afternoon, everyone. Thank you for joining us today for our business update call.
As we look into 2025, we remain optimistic on the potential for soquelitinib to provide a powerful new approach for the treatment of a broad range of immune diseases and cancer. Soquelitinib is well-positioned as a first-in-class oral therapy that selectively inhibits ITK to modulate and control parallel signaling pathways in the immune system.
Our confidence is backed by a strong and growing body of evidence both from our clinical efforts and preclinical research conducted by us and others. First, we have reported a 39% objective response rate from our phase one trial of soquelitinib in patients with relapsed T cell lymphoma. This included a 26% complete response rate, which is more than double the rate seen with standard chemotherapies.
Based on this data, we are enrolling a registrational Phase 3 trial of soquelitinib in patients with relapsed peripheral T cell lymphoma, and we have gained a significant amount of experience that we are applying to our other soquelitinib programs.
Second, we observed a favorable safety and efficacy profile from interim data from our Phase 1 trial of soquelitinib in patients with moderate to severe atopic dermatitis. This includes significant responses in the soquelitinib treatment groups compared to placebo or the clinically significant endpoints of Investigator Global Assessment or IGA 0 or 1, and Eczema Area and Severity Index, or EASI 75.
Third, preclinical data supports the potential of ITK inhibition in a broad range of indications, including solid tumors, immune conditions such as autoimmune lymphoproliferative syndrome, or ALPS, systemic sclerosis, pulmonary fibrosis, and graft-versus-host disease, and inflammatory conditions such as asthma, psoriasis, and inflammatory bowel disease. The data also highlights its mechanism of action, skewing differentiation to Th1 cells, reducing Th2 and Th17 cells and their downstream cytokines, and promoting a switch to two T regulatory cells that suppress inflammation.
Given the broad applicability of its mechanism of action, we view the potential of ITK inhibition as analogous to BTK inhibition, a category that members of the Corvus’ team, including myself, helped to develop. BTK inhibitors were first approved for B cell malignancies and then expanded into autoimmune conditions.
Today I will recap our previously reported data in atopic dermatitis and next steps for the trial. Share some detail on the recently initiated NIH trial in ALPS and highlight the upcoming milestones for soquelitinib.
In January, we reported interim data from the Phase 1 trial of soquelitinib in patients with moderate to severe atopic dermatitis. The trial includes four cohorts that are enrolling 16 subjects each at a 3:1 ratio of active to placebo, 12 active, 4 placebo. The trial is double blind, meaning the patient and the doctor do not know what they’re taking. The active medicine and placebo are indistinguishable tablets.
The company and the data review committee are not blinded. The treatment period is 28 days, and then we follow patients off therapy for another 30 days. The 28-day treatment period is relatively short compared to later-stage atopic dermatitis studies with other agents which typically treat up to 16 weeks or longer.
The primary endpoint is safety and tolerability. Secondary endpoints measure based on IGA and EASI scores along with patient reported measures of itch and biomarkers. The first two cohorts received soquelitinib doses of 100 mg twice a day and 200 mg once per day. The same total dose of drug was used in the first two cohorts. Based on our lymphoma studies, we know that 100 mg will provide 50% to 80% occupancy of the target, and 200 mg will provide about 80% to 100% occupancy.
In January, we reported data from 16 patients in cohort 1 and 10 patients in cohort 2, for which 28 days of treatment had been completed. In total, from the combined cohort 1 and 2, this included 19 patients treated with soquelitinib and 7 patients treated with placebo.
In the soquelitinib group, 26% achieved IGA 0 or 1 and 37% achieved EASI 75. Recall, these have been accepted as measures of clinical benefit and have been used as the basis for regulatory approval for several approved treatments for atopic dermatitis. In the placebo group, no patients achieved IGA 0 or 1 or EASI 75. No significant safety issues were observed and no clinically significant laboratory abnormalities were seen.
Cohort 3 of the trial, which administers a dose of 200 mg twice a day, that is twice the total daily dose we used in the earlier cohorts, is nearing completion of enrollment, and some patients have already reached the 28-day follow-up period.
The efficacy results so far in the trial, including full cohort 1 and 2 and the initial experience in cohort 3, have been positive and consistent with what we have reported to date. No patients in the active treatment groups received concomitant topical steroids or required rescue medications. One patient in the placebo group did receive concomitant topical corticosteroids.
In cohorts 1 and 2, two placebos experience flares in their disease during the 28-day treatment period, whereas no disease flares were seen in the patients receiving active drug during the 28-day treatment period, as well as the follow up period of treatment.
Soquelitinib has been very safe to date as well, with no patients requiring interruption of therapy. We now have experience in over 100 patients with lymphoma and atopic dermatitis, representing more than 9,000-patient days of treatment, including patients with lymphoma on therapy for up to two years.
We continue to believe that soquelitinib is an active medicine for atopic dermatitis with several advantages. Oral route of administration, attractive safety profile, a novel mechanism of action with an opportunity for unique positioning, including the potential to bridge between topical therapies and systemic injectables.
We plan to report data covering the first three cohorts at the Society of Investigative Dermatology meeting taking place May 7 to 10 in San Diego. Our abstract has already been accepted for an oral and poster presentation at this meeting.
Outside of atopic dermatitis, we continue to enroll patients in our registrational Phase 3 trial of soquelitinib in patients with relapsed PTCL. Recently we presented updated data from our Phase 1 trial at the T cell lymphoma forum with longer follow-ups showing that the median progression free survival is 6.2 months and the 18-month progression free survival is 30%. The median duration of response was 17.2 months.
PFS, or progression free survival, is the primary endpoint of our Phase 3 trial, which is comparing soquelitinib to either Belinostat or Pralatrexate, the standard of care agents with reported median PFSs of about 3 months and 18-month PFSs of under 20%.
We also have recently announced the initiation of enrollment in a Phase 2 trial of soquelitinib in patients with ALPS, autoimmune lymphoproliferation syndrome. This study not only addresses a disease with unmet need but will also provide additional information on the activity of selective ITK inhibition in a serious autoimmune disease.
ALPS patients are born with a genetic mutation in fast signaling that results in lymphoproliferation and a myriad of autoimmune problems such as anemia, neutropenia, thrombocytopenia, and others. Some of these patients go on to also develop malignant lymphomas.
The ALPS trial is being conducted under a clinical research and development agreement with the National Institutes of Allergy and Infectious Diseases at NIH. It will enroll up to 30 patients aged 16 years or older with confirmed ALPS based on genetic testing. There will be two dosing cohorts, 200 mg or 400 mg of soquelitinib twice per day for a period of up to 360 days.
The primary endpoint of the trial is efficacy determined by reductions in spleen and lymph node volumes as measured by CT scans. In addition, improvements in cytopenias, or lower blood cell levels, will be assessed by complete blood counts. Improvements in cytopenias can improve quality of life and overall health. And serve as a biomarker associated with ALPS disease activity, including autoantibody levels that are reactive with red cells, white cells, and or platelets. Secondary endpoints include safety and tolerability.
We are also planning a single-agent soquelitinib solid tumor trial in relapsed renal cell cancer, or RCC, representing a new approach to immunotherapy of this disease. We plan to initiate this trial during the third quarter of 2025.
Outside of soquelitinib, we also continue to advance our other clinical stage development programs. We have been one of the leaders in the development of adenosine A2A receptor antagonists for the treatment of cancer with ciforadenant. This includes our Phase 1b/2 clinical trial that is being conducted in collaboration with the Kidney Cancer Research Consortium.
The trial was evaluating ciforadenant or ciforadenant as a potential first line therapy for metastatic renal cell cancer in combination with ipilimumab and nivolumab. The study has reached full enrollment of 60 patients at sites including MD Anderson, Vanderbilt, Duke, and the University of Pennsylvania. The patients are being followed, and we anticipate our partners at the Kidney Cancer Research Consortium will present data from the trial sometime later in 2025.
Finally, I should mention that we are advancing several second- and third-generation ITK selective inhibitors designed to preferentially affect particular ITK signaling pathways.
Summarizing the outlook for the remainder of 2025, we remain focused on advancing the broad opportunity for soquelitinib, which has several potential upcoming catalysts. This includes, number one, additional data from the Phase 1 trial in atopic dermatitis in May at the Society for Investigative Dermatology meeting. Number two, full data from the Phase 1 trial on atopic dermatitis in the third quarter. Number three, initiating a Phase 2 clinical trial with soquelitinib in solid tumors in the third quarter of 2025, with initial data anticipated in the first half of 2026.
Number four, initiating a Phase 2 atopic dermatitis trial in late 2025. Number five, continuing to activate sites and drive enrollment in the registrational Phase 3 trial of soquelitinib and PTCL driving towards interim data in late 2026. And depending on enrollment trends, it’s possible we could see initial data from the Phase 2 ALPS study in late 2025 or early 2026.
Our current cache gives us runway into the first quarter of 2026, allowing us to execute on these important milestones and further demonstrate the value of our programs and in particular the significant opportunity for ITK inhibition in immunology and cancer. We 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
Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. (Operator Instructions)
Jeff Jones, Oppenheimer.
Jeff Jones
Good afternoon, guys, and thanks for taking the question.
Lots of data updates to come, so really exciting time for you guys. I guess, starting out on the AD front and the update in May, will the — should we expect full data on cohort 3 as well as additional patients on cohort 2? And then as you think about the efficacy hurdle there, what do you guys have in your head to move this ahead into the Phase 2A that you just mentioned or and just competitiveness in the field?
Richard Miller
Okay. So Jeff, the, meeting in May, the Society of Investigative Dermatology, we intend to report the full data set on cohort 1, the full data set on cohort 2. We’ve already completed enrollment and follow up in those two cohorts. Cohort 3 is almost completed enrollment, a 28-day follow up is coming in on patients now. We’re also going to have additional 1-month follow up beyond that. So we’ll have the full data for cohort 1, 2, and 3. I also expect to have biomarker data for those first 3 cohorts as well.
Jeff Jones
Okay, great. And then just in terms of the success hurdles and efficacy bar that you guys are looking at.
Richard Miller
Well, first of all, we’re pretty pleased with the efficacy we saw in cohort 1 and 2. Let me remind you, that’s 28 days of treatment. We see what a 30% difference in some of these 25% to 35% difference between placebo, which was zero in cohort 1 and 2, and our actives, that’s a pretty good number. And that number sustained or improved would be very good in our opinion.
Now, of course, many people are asking about what would happen if we increased the duration of therapy, and that’s something that we’re thinking about and will come in time. So we’re pretty pleased with the efficacy results we have to date in terms of a competitive landscape.
Of course we’re oral, we have a different mechanism of action. Safety looks really good so far, convenience, the study — the design of our study was really intended to determine whether or not selective inhibition of ITK had some role in immune disease. Is there some signal, some indication of efficacy in an autoimmune disease? And I think we’ve got that.
Now, of course, as we think about Phase 2 trials and beyond, we’ll begin to think about what, what’s required for registration, etc. But I think from a competitive standpoint, to my knowledge, we’re the only selective ITK inhibitor. I know there’s some other companies that have ITK inhibitors and are talking about it now, but they’re not selective and we view that as critical in the biology. And so I think we’re in pretty good shape on this.
Jeff Jones
Great. Thanks, Richard. I’ll hop back in queue.
Operator
Aydin Huseynov, Ladenburg Thalmann.
Aydin Huseynov
Hi, good afternoon, everyone. Richard, congratulations with the progress this quarter. I’ve got a couple of questions here.
So regarding the potential cohort 4, so could you clarify your plans for cohort 4, whether you still would like to enroll in 40 — 400 mg? And just if you could give us like a general idea what is the difference in terms of the doses, I mean, why would you like 400 mg doses as compared to the oncology trial where you maximum — what’s, where your optimal dose is just 200 mg.
Richard Miller
Thank you, Aydin. Good question. So just for the benefit of everyone else, cohort 1 was 100 mg BID, cohort 2 was same, total dose 200 mg once a day, cohort 3, 200 mg twice a day, and cohort 4, as you indicate, would be 200 — 400 mg at the same total dose one time. So before deciding whether we’re going to do cohort 4, that is the plan. But we want to look at the full data set from cohort 3.
We already have cohort 1 and 2. We’ll look at the data from cohort 3, and then we’ll decide whether we would do that or not. Right now the plan is to do that, although we are thinking about other possibilities, like, extending duration of therapy. Each of the doses 100, 200, 400 is very good occupancy of the receptor.
And, of course, as I’ve indicated in previous calls, we don’t really know what it takes to get a clinical effect or biologic effect in atopic dermatitis, whether you really need a 100% occupancy. But even at our starting dose of 100, there’s pretty good occupancy. So right now the plan is to do cohort 4, but before we decide definitively on that, we want to look at our data.
Aydin Huseynov
That makes sense. And regarding the prior therapies, I know that many of those patients previously failed to fix in first two cohorts. How about the cohort 3? Did you see the patients, sorry, they’re DUPIXENT naive, sorry, the first two cohorts. So is the cohort 3 also sort of mostly DUPIXENT naive patients?
Richard Miller
We have deliberately searched for sicker patients in cohort 3. So we do have more DUPIXENT and systemic treatment failures in cohort 3. We also have, so far, I mean, we’re not done with the cohort. We do appear to have higher baseline EASI scores. So we’ll have to look at that and we’ll see how that turns out, whether there’s a particularly good or effect in [2P] failures, we don’t know yet. We don’t really know how that variable fits in yet.
Aydin Huseynov
Okay, understood. And the last one is the biomarker question. I think you mentioned that you will be talking about biomarkers in May. So could you elaborate a little bit on that? What kind of biomarkers are out there for atopic dermatitis?
Richard Miller
Well, I would say that some of the work that we presented back in January on biomarkers or in December, is being confirmed in our ongoing studies. In addition, we’ve picked up a couple of other things that I think are quite interesting. I’ve been talking about, we’ve been talking and studying these deregulatory suppressor cells and other cells, and I think those are turning out to be extremely interesting.
We continue to see a very durable effect of our treatment in patients who receive the drug. And, I mean, it’s a small data set, it’s very early, but it’s also very provocative at this point.
Aydin Huseynov
Okay. Understood. Thanks so much.
Operator
Graig Suvannavejh, Mizuho Securities.
Hi, this is Sam on for Graig. Thanks for taking our questions. Maybe one on ALPS, just given that it’s a new indication. Can you just tell us, in terms of like the addressable patient population that you guys are kind of due diligence. And also, what, if there’s a subset of patients that would be ideal candidates for soquelitinib among people with ALPS. Thank you.
Richard Miller
Okay, so in the United States, so ALPS or A L P S, autoimmune lymphoproliferative syndrome is a genetic disease. You’re born with it. I’ll give you a little background on the disease. Babies are born with it. They, at around age two, they start to develop anemia and big spleen and lymphadenopathy, infections, and they get a diagnosis made, of course. And then they’re on lifelong, immunosuppressive therapies, cyclophosphamide, steroids, mTOR inhibitors, things like that.
And they can be on that a long time. The disease is not curable, and they’ll have waxing and waning adenopathy and cytopenia, anemia, neutropenia, thrombocytopenia. They can live 30, 40, 50 years old now. But they suffer a lot of the complications. They have massive splenomegaly, that’s another problem they have with sometimes can rupture.
A subset of these patients, maybe 10%, 20%, go on to develop malignant lymphomas. Usually they’re B cell lymphomas. But the abnormal cell in the ALPS is a T cell. It’s an abnormal T cell called the double negative T cell that does not have CD8 or CD4. I won’t go into the biology of it, but it has a lot of ITK expression.
And in our work looking at the effect of soquelitinib in various murine autoimmune models, we found that the same, there’s a strain of mouse called the MRLLPR negative mouse that has the very same mutation that you see in these patients, same disease basically, genetically. And when we treated animals with our drug, it was dramatically effective, really dramatically effective.
Cytopenias go reverse and become normal, splenomegaly, lymphadenopathy, all that thing, basically these animals become normal. And so that prompted us to say, hey, let’s go treat the human genetic — identical genetic disease in humans. And that led us to the NIAID that has a very big collection of these patients.
Now, most pediatric hospitals have patients like this and you asked about the market. There are about 2,500 patients with this disease in the United States currently. They live a long time. They live to be age 40, 50, as I said, some die sooner, but that in general is their lifespan. .
I don’t think there’s any particular subset that would be, not to our knowledge now, that would be more or less amenable to this therapy. So we just don’t know. Sometimes there are slightly different mutations in patients, but the main problem in the mouse and in the human beings is that their cells, their lymphocytes do not undergo apoptosis.
Now, there’s a very strong connection between T cell receptor signaling an apoptosis. Think about it. When there’s antigen or you have an infection, you want your T cells to proliferate, kill off the infection, but then you want those T cells to go away when the infection is eliminated. That requires apoptosis. That is regulated by ITK. ITK has many roles in various signaling pathways, and when you block ITK, you restore apoptosis to these cells. And so that’s the rationale for this.
So basically, this is a treatment that I think you would take for a long time. And, given the safety we’ve seen so far, we think this could be very important. Now, also from a regulatory standpoint, this is not a disease I don’t think where you’re going to be asked to do big randomized clinical trials. So that’s something else to think about.
We’re very excited and interested in this disease. You can tell by my long-winded answer. And then finally, what this does is, I mean, this is really an opportunity to look at the effect of our drug on all sorts of autoimmune manifestations, anti-red cell antibodies, antiplatelet antibodies, all that sort of stuff which we think will have important relevance to other autoimmune diseases.
Does that answer your question? Probably.
Definitely, very insightful. Thanks so much, Richard, for taking our question.
Operator
Roger Song, Jefferies.
Cha Cha Yang
Hi, this is Cha Cha Yang on for Roger. I’m looking towards your Phase 2 for AD, and I’m wondering if you can give some color on what subpopulations within the disease you’re hoping to target. More specifically, if you could talk about aspects like prior medication use based on EASI scores, and then any geography and demographics insights, that would be great.
Richard Miller
Well, that’s a pretty tough question considering we haven’t finished Phase 1 yet, but moderate to severe atopic dermatitis, failed topical corticosteroids, or a systemic therapy, very similar to the criteria we’re using now. I don’t know if I would require, I mean, baseline EASI scores to be moderate or 16 or greater. So I don’t think we would have any requirements beyond that.
I think a typical study would be look at two different dose levels, plus a placebo, so probably a three-arm study, maybe around 200 patients total. But that’s an, kind of, an approximate answer at this point. But that’s all pretty standard.
Cha Cha Yang
Sounds good.
Richard Miller
And but in the endpoint would be either EASI 75, those who achieve EASI 75 or IGA 0 or 1. That’s pretty standard in point now.
Cha Cha Yang
Great. Thank you for that.
Operator
Li Watsek, Cantor.
Daniel Browder
Hi team. This is Daniel Browder on for Lee. I have a question about the prioritizing of opportunities for soquel in oncology versus inflammatory disease and how you look at it as you move into later stage trials.
Richard Miller
Okay. Well, right now we have soquelitinib in a Phase 3 registration trial that could produce data in less than two years. And so we’re pushing on all fronts as aggressively as we can. So the strategy is try to get an approval in lymphoma, try to get an approval in immune disease. Now, we are aware of some of the issues with having a similar-same drug for autoimmune disease and cancer.
We have a very aggressive program in second- and third-generation compounds. We also think that the dosing and duration of therapy are going to be very different in oncology versus immunology. A very good example would be RITUXAN, for example, which, came out of my lab at IDEC.
RITUXAN is approved for lymphomas, as it’s also approved for rheumatoid arthritis, pemphigus, ITP, and probably a few more autoimmune diseases. And it is really no issue with pricing because the treatment regimens are such that on a per milligram basis, it turns out to be pretty similar.
So our strategy now is push forward on all these fronts and get deeper and deeper into the pipeline and, at some point of course, we recognize that autoimmune diseases is a vast undertaking. There’s many different diseases and competitive areas and, of course, we would at the right time consider some sort of a collaboration or partnership.
Daniel Browder
Okay, cool. Thank you so much for that detailed answer. And the other question we were wondering about is you alluded to earlier a little bit. The delay in the presentation of cohort 4, is that more driven by your waiting and seeing of cohort 3 results or has there been a delay in enrollment more generally?
Richard Miller
No delay in enrollment. We’re waiting to see the data from cohort 3, and we’ll make a decision about proceeding with cohort 4, or maybe, extend one of the other cohorts.
Daniel Browder
Okay, cool. Thank you so much.
Operator
Sean Lee, H.C. Wainright.
Sean Lee
Hi. Good afternoon and thanks for taking my question. I just have one on the upcoming solid tumor study that’s been planned. I was wondering whether there are specific indications that you feel are most suitable for circulated, or would it be just a general basket study. And also, would you need to do a dose escalation again or would you start with the PTCR dose. Thanks.
Richard Miller
So the first part of the question, which tumors? We will start with the immune responsive tumors. So what are those? Those are renal cell cancer, lung cancer would be good. Those would be probably the top choices to start because you want tumors where you think there’s some evidence for immunotherapeutic effects. Melanoma might be another one, although that’s a much less common disease and is adequately, somewhat adequately, treated by other treatments.
So I would say, renal, lung, I don’t think we need to do a dose escalation, but certainly you would want to do different doses. You’d want to look at different doses. It wouldn’t be a dose escalation in the usual sense that you’re thinking of like a Phase 1 oncology study. But you would probably want to look at different doses.
But we have a pretty good handle now on the dose and we have a very good pharmacodynamic marker, which is we know what it takes to saturate the ITK target. 100, 200, 300, or 400, we’re all in the same ballpark. They’re all going to be give you pretty much the same, similar findings.
Sean Lee
Great. Thanks for that.
Operator
Thank you. There are no further questions at this time. I would not have a call back to Mr. Richard Miller for any closing remarks.
Richard Miller
Okay, I want to thank everyone for participating in the call, and we look forward to additional updates in the future. Thank you very much.
Operator
Thank you and this concludes today’s call. Thank you for participating me all disconnect.
