Afternoon, everyone. Welcome back to Oppenheimer's Annual Healthcare Conference. I'm Jeff Jones, one of the analysts here on the biotech team, and I'm delighted to welcome Jeff Arcara, the Chief Business Officer of Corvus Pharmaceuticals. Jeff, I'm going to hand it over to you to take us through the latest on the story.
Thank you, Jeff, for the invitation to present today at the Oppenheimer Healthcare Conference. My name is Jeff Arcara. I'm Chief Business Officer at Corvus. Today, we'll provide an overview of the company and an update on the progress of our pipeline, with a focus on our lead program, soquelitinib. Soquelitinib is a novel potential first-in-class oral therapy that represents a significant advancement in the treatment of atopic dermatitis, as well as other immune diseases. On my screen, you should see a safe harbor statement and a forward-looking statement, which you can be found and reviewed in our presentation deck on the Corvus website. Who is Corvus? What do we do? And most importantly, what do we do differently? Corvus is a clinical-stage company, developing first-in-class immune modulators with a broad potential in oncology and immune-mediated diseases.
Our lead asset, soquelitinib, is currently in phase III registrational trial for peripheral T-cell lymphoma, as soon to be in a phase II trial in atopic dermatitis. Soquelitinib is a novel oral therapy that has demonstrated compelling safety and efficacy profile to date in markets that are really dominated by injectables. It represents a pipeline and a product opportunity with expansion to multiple follow-on indications. The program is supported by strong intellectual property, including issued composition of matter protection through 2037, and that doesn't include any patent term extensions. Beyond soquelitinib, we have, we're developing a number of next-generation ITK inhibitors to further expand and capitalize on our ITK platform across a broad range of additional diseases and indications. Let's look a little deeper at our pipeline.
As I mentioned, our phase II registrational trial in lymphoma is ongoing, with interim analysis expected by year-end 2026. We're about to start our phase II clinical trial in atopic dermatitis. This is a prospective, randomized, placebo-controlled trial in moderate to severe patients with data expected in approximately 18 months. As I mentioned, pipeline and a product potential. In addition, we'll be starting 2 phase II proof-of-concept studies this year in asthma and HS, and we'll talk a little bit more about the science and the rationale to support those studies in a few slides. First, how does soquelitinib and target ITK inhibition work? ITK stands for interleukin-2-inducible T-cell kinase, which is involved in T-cell receptor signaling, as shown on the left-hand side of this cartoon.
Genetic studies have actually shown that if you precisely knock out the ITK gene and nothing else, that you actually inhibit Th2 and Th17 cells, and there are resulting cytokines that come with those cells. If you look at the right-hand side of the slide, the lower right-hand side, you see those cytokines include IL-4, IL-5, IL-13, IL-17, and many others that are involved in autoimmune and inflammatory and fibrotic and allergic diseases. With that, if you look at the upper, right-hand side, we still permit differentiation and skewing of Th1 cells. These Th1 cells help to fight cancer and to reject and fight off viral-infected cells. Of note, it's really important that you only want to block ITK and not RLK, which stands for resting lymphocyte kinase, 'cause if you do block RLK, you'll actually cause immune dysfunction.
In addition, the science has gotten a little more interesting. We now know that if you block ITK with soquelitinib, you not only get Th1 skewing, but you also get a shift or a switch in pro-inflammatory Th17 cells to become functional, actually, Foxp3 Treg cells. Potentially inducing a lasting remittive effect, which is a holy grail for immune therapy. And we'll talk a little bit more about this durable effect in an additional slides. What makes Corvus and soquelitinib so unique? Essentially, it's our chemistry, which focuses on covalency and ITK selectivity to create highly differentiated drug properties.
This data, if you look at the bottom right, was published in Drug Discovery, and as you can see in the table on the left-hand side, as well as in the dendrogram, so-called, is very specific for ITK and spares other kinases, such as RLK and BTK. That's not only important for efficacy, but it's also very important for safety. Why do I say that? First, ITK has very limited tissue distribution. It's found only on T- cells and NK cells. Second, we have a drug that's very specific for that target, so that off-target activity is actually limited. It's this combination of targeted binding and restricted tissue distribution that really supports a favourable safety profile and a strong, you know, therapeutic window. How does soquelitinib compare to other approved AD therapies?
Again, as I mentioned, we affect multiple inflammatory pathways, which would meaningfully differentiate us from other therapies in the treatment landscape. While most therapies will block either a single cytokine or a pathway, soquelitinib works upstream, modulating multiple drivers of disease, such as IL-4, IL-5, IL-17, IL-31, all of which are important for atopic dermatitis. If you look at the upper right-hand side, it also impacts important immune cell populations, including Tregs and ILC2s, which also supports a more comprehensive immune rebalancing approach. Again, this broader mechanism sets us apart from our current therapies, and believes it gives us, you know, differentiation, number one, in treating a broader set of I&I diseases, and number two, potentially being able to treat patients that have failed other therapies.
You'll see that reflected in our, in our data. As I just mentioned, this upstream approach not only sets us apart for treating AD, but also in many other immune and inflammatory diseases. If you look at this slide, we have potential utility in Th2-driven diseases such as AD and asthma, Th17-mediated diseases such as psoriasis and HS, as well as IL-5-associated allergic disorders and fibrotic indications such as systemic sclerosis, IPF and IBD, such as Crohn's and colitis. When you look at all of these diseases together, there's a very significant commercial opportunity, and it's large and growing. As you can see on the left-hand side, the Th2 and Th17 team diseases impact over 130 million patients in the G7.
If you look at the right-hand side of the slide, the IM market is expected to grow to $170 billion in sales by 2030, and oral agents only represent a small fraction of that potential. A very large and unmet need and opportunity for a novel, safe and oral agents. There aren't a lot of oral agents actually in development. Let's look a little deeper at our clinical trial results, which show that soquelitinib could be a leading therapy in AD, and it's oral. The data confirm soquelitinib demonstrating activity and a favorable safety profile in AD.
If you look at the left-hand side of the slide, you know, reading from left to right, at eight weeks, we saw 75% of patients achieve an EASI-75, 25% EASI-90, and 33% achieve IGA 0/1, with a mean EASI reduction of 72%. Importantly, extending duration of treatment from four to eight weeks resulted in deeper responses without compromising safety or tolerability. The durability of the effect is notable when we see continued reductions in EASI scores even after the treatment stopped. We also see efficacy that was consistent across all patient populations with comparable responses in both systemic, treatment-naive, as well as previously treated individuals. In addition, biomarker findings include induction, including induction of Treg cells, also demonstrate activity as well as immune rebalancing.
This next slide actually looks at the results comparing four weeks of treatment, which is cohorts 1 through 3, and eight weeks of treatment, which is Cohort 4. If you look at specifically at EASI-75, EASI-90, IGA 0/1, if you look at the right-hand side of the slide, cohort confirms that we see strengthening from Cohort 3 in terms of a larger sample size and randomization. If you look at the right-hand side, Cohort 4 showed a 75% of patients treated achieving EASI-75, 25% EASI-90, and 33% IGA 0/1.
By comparison, again, if you look at the right-hand side, the two placebo patients in Cohort 4 achieved EASI-75, both who were actually systemic treatment-naive, and no placebo patient achieved an EASI-90 or IGA 0/1. Also, none of the seven placebo patients with prior systemic therapy reached an EASI-75 or an EASI-50, whereas in the so-called group, we had three of five previously treated patients achieve EASI-75. Let me take a minute, and we'll remind everyone about the phase I clinical trial design in moderate severe AD. This study is a randomized, placebo-controlled, blinded study by both patients and investigators, and no concomitant topical steroids are permitted.
Eligible patients will have failed at least one prior topical or systemic therapy, including those who have not responded to prior systemic therapies. This is a population that's actually often excluded from other AD trials. If you look at the center of the slide, Cohorts 1 and 3 each enrolled 16 patients, randomized 3 to 1 versus placebo for 28 days, and then we had a 30-day off treatment. Doses included 100 milligram BID, 200 milligram QD, and 200 milligram BID, with 200 milligram BID selected based on our target occupancy data in alignment with our phase III lymphoma program. Based on these encouraging results, Cohort 4 was actually extended to eight weeks of treatment, and we'll talk a little bit more about the rationale in the next few slides.
It enrolled 24 patients, randomized 1 to 1, again, with 200 milligram BID. This study was conducted in 17 centers across the US. Here are the baseline characteristics for the full cohorts. Again, this is a total of 72 patients that are enrolled across all full, all cohorts, 48 on active, 24 on placebo. If you look at on the right-hand side, the data for Cohort 4 patients is shown on the right. It's very similar to Cohort 3. The age, the proportion of African Americans, prior systemic therapy, and the mean baseline EASI score are all very similar. The arms are well-balanced, and if anything, placebo is more favorable.
It's also important to note that 50% of patients in Cohort 4 had received prior systemic therapy, and we'll look at those patients in more detail. Before, you know, turning to Cohort 4, let's briefly review the efficacy results from cohorts 1 through 3, and again, this was 4 weeks of treatment. As previously presented, the strongest activity was observed in Cohort 3, at the 200 milligram BID, which is in the center column of the table. At 28 days, Cohort 3 patients taking the 200 milligram BID achieved EASI reduction of 64.8%. You can see that at the top there, compared to 34.4% for placebo, which is a 30% placebo adjusted difference.
EASI-75 was achieved in 50% of Cohort 3 treated patients, one patient reaching EASI-90. If you will notice on the right-hand side, lower right-hand side, no placebo patients achieved EASI-75, -90, or IGA 0/1, that's likely reflecting, first, the short 28 days of treatment duration, but also, as we just talked about, inclusion of more treatment experienced and more refractory treatment population. Essentially a more sicker treatment population. Here are the kinetics of response for the first three cohorts. To orient you on the slide, first, that white area in the beginning is the 28 days on treatment.
The gray area on the right-hand side, patients are off treatment, and if you look at the curves, the orange curve is placebo, and then the red gray, and blue curves, are in the middle, are Cohorts 1 and 2, and then the green curve at the bottom is Cohort 3. Sorry, let me go back here. As you can see, you know, Cohort 3, showed a more rapid and deeper reduction in EASI scores as compared to Cohorts 1 and 2. The curves are continually decreasing at day 28, so that's what suggested to us that maybe studying a little bit longer than 4 weeks, we would see deeper responses. Again, that's why we changed the Cohort 4 to two months of therapy.
We also saw, if you look at the right-hand side, that responses persisted beyond 28 days of treatment. For most other treatments, once treatment stops, most will see return of disease in actually only a few weeks. If you look at, you know, a slide that highlights, you know, this slide actually highlights new durability data that we have from Cohort 3 following our protocol amendment that allowed for extended follow-up. As you can see, responses were sustained and in some cases, further improved through day 118, and this represents roughly three months of treatment. You know, these findings suggest that a potential durable disease control beyond the active dosing period.
You know, mechanistically, we believe that durability may be driven by the induction of T regulatory cells, which is consistent with our preclinical data that we observed with an increase in circulating T reg cells. You can see that in that box, in the, in the white box in the center, we actually see a significant separation with Cohort 3 versus placebo, and the two cohorts with an increase in T reg cells. Taken together, these findings support the potential for soquelitinib to induce T regs and promote a durable immune response and regulation, and hopefully potentially sustain disease control. You know, and for context, and as an example of that, this slide actually shows published data from a phase II trial with abrocitinib, which is a JAK inhibitor, and this includes follow-up beyond the 12-week period.
You can look at the center of the slide there. You can see that the lower two curves are the doses, the approved doses of 100 and 200 milligram doses, dosed daily. What you can see there is a rapid rebound in disease activity beginning after as early as one week, and you can see that at week 13. Similar patterns of relapse, you know, can be seen in other approved therapies, and importantly, we have not observed this rebound effect with soquelitinib so far, you know, further supporting potential differentiation and durability of the response. How about itch? This slide talks and highlights our patient-reported itch outcome, using the PP-NRS scale, comparing Cohort 3 to placebo.
We observed a meaningful reduction in itch with a notable proportion of patients achieving a ≥4-point improvement, which is the threshold by regulators for clinically significant. Importantly, because elevated baseline itch was not required for enrollment, not all patients were eligible to reach this threshold. Cohort 4 itch data is not yet available. Overall, conclusions from the data and the Cohort 1 through 3 that we just talked about, we see that soquelitinib appears to be safe and effective compared to placebo, with a 28-day treatment regimen, and disease remissions appear to be durable. Now let's change gears, and we'll talk and look at Cohort 4 data. Again, this is eight-week efficacy data at 200 milligram BID.
You can see on the slide the mean percent reduction in EASI score is 72% versus 40% placebo. That p-value is actually 0.035. 75% of patients achieved EASI-75, 25% EASI-90, and 33% achieved an IGA 0/1. Of note, 11 of 12 patients achieved an EASI score, EASI-50 score of 92%, so significant reduction there. You can see on the right-hand side, 2 placebo patients achieved an EASI-75. On this table, we show EASI-75 for placebo in 2 out of 10 or 20%. We did have two additional placebo patients that were non-compliant.
They missed the day 56 evaluation, and on later evaluations, they never achieved an EASI-75, which that would make the proportion of 2 of 12 or 17%. Of note, you know, two placebos required rescue meds due to disease flare and none in the active group. Our conclusion from these data show that soquelitinib is superior to placebo in almost in every or actually in every efficacy endpoint that we've evaluated. This is the curve, you can see the response curve for Cohort 4. You can see a very clear separation of curves from the 1st visit, which is day 15, that separation continues from placebo day through day 28.
You can see in the center of this slide is the treatment period, which is two months, in the right-hand slide, they're off treatment. You can see that the curve that we actually see further increases out to day 56 without a plateau and a steady downgrade of the slope. The day 56 p-value is actually 0.035, and this is our primary efficacy endpoint, and we see a continuation of disease control in the post-treatment 30-day follow-up period out to day 86. These data confirm our hypothesis that, you know, from cohorts 1 and 2, that extending the treatment duration out to eight weeks would deepen our responses. As I mentioned earlier, we've allowed patients who had prior systemic therapy to be in our study.
This slide shows the prior systemic therapy experience in cohorts 1 through 4. Overall, we had 35% of patients that had a prior therapy, with 50% in Cohort 4. As you can see, DUPI is 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 non-responsive. That is they weren't responsive to their treatment, we'll talk a little bit more about those patients in the next few slides here. This slide shows our outcomes from all patients, and I think this is probably one of the most important slide that we'll talk about. This is all patients that are studying, as well as patients that are treated with prior systemic therapies.
On the left-hand side of the slide, we show the response curves for all soquelitinib patients, treated patients, and all placebo patients. In total, that's 72 patients, 48 on drug and 24 on placebo. The efficacy results in all treated patients is strong, with a p-value of 0.003 at day 28. At the right-hand side, we show response curves for those patients that were on prior systemic therapy. You can see that there's a very clear separation in both cases. These curves are very similar for patients receiving soquelitinib, indicating to us that soquelitinib is not affected by prior systemic therapy experience. Note that placebo patients who receive prior therapies do worse, indicating that prior systemic therapy is unfavorable, and you can see that in the placebo recurve.
This results in a greater separation of the curve from the soquel arm. This essentially is the same slide, but we've broken out just cohorts 3 and 4, which is the 200 milligram BID dose. You can see that on the left-hand side, again, on the right-hand side is those who've received prior therapies. This is the same placebo group as noted earlier in the comparison slide, the previous slide. Again, we see a clear separation of the curves with wider separation in patients with prior therapy. Again, the soquel, soquelitinib curves are nearly identical, indicating that the treatment effect is maintained in both prior treatment, naive and experienced patients.
Turning back to the patients that were resistant to their last systemic therapy, we identified at least 6 patients who were actively failing prior systemic therapy at study entry, a population typically excluded from most AD trials. All were excluded in cohorts 3 and 4, including 4 on active therapy and 2 on placebo. If you look at the bottom of the slide first, both placebo patients experienced disease flares, requiring a rescue medication. You can see they were on DUPI and Rinvoq. In contrast, if you look at the top of the slide, you can see 3 of the 4 patients treated with soquelitinib improved. Two achieved EASI 90, one had a 27% reduction in EASI score, and one patient didn't respond.
Notably, this was the only patient out of the 12 that actually failed to reach an EASI-50. Again, these data demonstrate that, you know, soquelitinib remains active in treatment experienced or refractory patients with outcomes that are, you know, comparable to treatment-naive individuals, despite severe baseline disease. Again, supports a differentiated mechanism action and the lack of resistance due to prior systemic therapies. Let's turn to safety. Of course, safety in atopic dermatitis is paramount. Now let's look closely at safety on the next two slides. As you can see from this slide, no new safety signals were seen in Cohort 4 with the longer eight-week treatment duration. Reported AEs are similar in both placebo and active groups, and no significant lab or abnormalities were observed.
On this next slide, we show AEs of special interest. Essentially, there's nothing to report here. There are no hepatic abnormalities, there's no changes in LFTs, infections were similar and treated in the placebo group. We didn't see any problem with conjunctivitis, of course, or injection site reactions, of course, because we're oral, which can be bothersome to other patients. You know, in addition to the clinical data, we also have supportive data and biomarkers. These studies are still ongoing, we'll present this data at an upcoming meetings, including AAD and SID meetings over the coming months. The biomarker data, you know, reinforce soquelitinib is working upstream and broadly across immune pathways. If you look at the left-hand side, we see sustained reductions in IL-4 in cohorts 3 and 4, extending beyond treatment.
We see early and pronounced reductions in IL-5, beginning as early as day eight, and evidence of Th2 cell reduction on single-cell analysis, if you look at that center slide. We also observe a decrease in IL-17 and TARC, along with modulation of the JAK-STAT signaling pathways. Overall, the durability of the IL-4 suppression aligns with our sustained clinical response, while the IL-5 change suggests a rapid biological engagement. All of this is suggesting that soquelitinib will affect multiple cytokine and cellular functions involved in inflammation. How does our data compare to other agents? You know, here we show the endpoints of EASI-75, IGA 0/1 for approved biologics and JAK inhibitors along for versus soquelitinib.
If you can look at the right-hand side of the slide, you can see our data at 4 and eight weeks for cohort three and four are very competitive with other approved agents. At 16 weeks of treatment, which includes JAK inhibitors, again, we have a sicker patient population. You know, we believe these results, you know, we've obtained so far, place us among, you know, one of the most active agents, oral or injectable, approved or under development for AD. Now I'd like to discuss a little bit of our upcoming plans, specifically looking at our phase II AD trial, which will start very shortly. This trial is planned to enroll 200 patients with moderate to severe disease. They'll be randomized into 1 of 4 cohorts, with 50 patients per each cohort.
If you look at the center of the slide, you can see the doses we'll study is 200 milligrams QD, 200 milligrams BID, and 400 milligrams QD, along with placebo. The treatment duration is 12 weeks, with an off treatment, follow-up period. If you look at the right-hand side, the primary endpoint is medium reduction in EASI score at 12 weeks, which is a typical endpoint for phase II AD studies. This study will be an international study, and as I mentioned, this will be opening very soon in Q1 2026. You know, we're excited about starting the phase II trial study, AD study, because we see a tremendous market opportunity in front of us.
As you can see on this slide, AD affects approximately 30 million patients across the G7, and the market is projected to grow from approximately $12 billion in 2023 to $28 billion in 2030, and I've seen other estimates of growing up to $50 billion. You know, currently, only about 10% of the roughly 3 million moderate to severe patients that are eligible are taking advanced therapies and treated today. When you look at failure rates, safety concerns, the injection burden, there remains a significant unmet need, creating, you know, a compelling opportunity for a differentiated, you know, first-in-class oral therapy. Again, there aren't a lot of oral therapies that are in development.
Well.
One slide I'd like.
We're actually.
I can close up.
Yeah, just close out on the.
Okay.
Yeah.
Why don't I summarize? In summary, soquelitinib is a first-in-class selected ITK inhibitor, right, with a novel mechanism and is positioned well for treating AD in a broad range of diseases. The clinical data demonstrates we have a well-tolerated and active drug with durable responses. You know, we have a differentiated mechanism working upstream on blocking multiple cytokines, and we have a number of milestones that are coming up in 2026, including the start of our phase II AD trial, the start of our proof of concepts trial in asthma and in HS. We'll also have some data presentations at AAD and SID. Finally, we're continuing our phase III registrational trial in PTCL, with an ongoing, which is ongoing, and we'll have interim analysis by year-end.
With that, I'll stop there, Jeff, and hand it back to you.
Fantastic. Really exciting program, obviously fantastic data, and, you know, from the market reaction, I think you've really, convinced folks now about ITK and soquelitinib across a lot of indications here now with the validating data in atopic dermatitis. With that, I'll close things out. Thank you very much for the presentation today, and hope you have, some great meetings, at the conference.
Thank you, Jeff, and thank you for the interest in Corvus.
Great.