Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Corvus Pharmaceuticals Investor Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. 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. Thank you for joining us for the Corvus Pharmaceuticals Conference Call to provide an overview of interim data from the Phase I clinical trial of soquelitinib for the treatment of atopic dermatitis. 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. Joining me on the call from the company are Dr. Richard Miller, Chief Executive Officer, Leiv Lea, Chief Financial Officer, Dr. James Rosenbaum, Senior Vice President of Research, and Jeff Arcara, Chief Business Officer. Also joining the call is Dr.
Albert Chiou, Clinical Associate Professor of Dermatology and Director of Clinical Research in the Department of Dermatology at Stanford University Medical Center, who is one of the investigators in the Phase I trial. The executive team will open the call with some prepared remarks, followed by comments from Dr. Chiou and a question-and-answer period. Turning to Slide 2, 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 most recent quarterly report on Form 10-Q 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. Richard?
Thank you, and good morning to everyone. I appreciate you joining us at this early hour to review our progress and results from our Phase I trial with soquelitinib for the treatment of atopic dermatitis. We are very pleased to review these data with you, covering the complete safety and efficacy from our first cohort and an update on preliminary data from our second cohort. Let me start by highlighting three key takeaways from the data. First, the early data from the first cohort show a favorable safety and efficacy profile. Second, we believe these data support a product profile that could be highly attractive for physicians and patients, particularly when compared to existing treatment options, including injectable biologics.
Third, we believe these data provide proof of concept for ITK inhibition as a potential platform opportunity in immune diseases based on its ability to modulate and control parallel signaling pathways in the immune system. First, I would like to review some of the properties of soquelitinib as shown on this slide. We believe that soquelitinib is inhibiting a high-value target made possible by the specificity of the drug. soquelitinib is orally administered in tablet formulation and may have the potential for biologics-like activity. It may have the potential to become the bridge between topical therapies and injectables. Its mechanism of action is unique as it affects multiple parallel signaling pathways in critical immune cells. This mechanism of action may provide comprehensive blockade in the production of multiple cytokines while inducing active immune tolerance through its action on T regulatory cells.
These features suggest that soquelitinib could have broad activity in a wide range of immune diseases as well as cancers. Let's look at the mechanism of action in a bit more detail as shown on the next slide. ITK, or interleukin-2 inducible T cell kinase, is an intracellular enzyme with very limited tissue distribution. It is expressed in T cells, NK cells, and type 2 innate lymphoid cells, or ILC2s. ILC2s are resident lymphocytes present in the skin, lung, and gastrointestinal tract. ITK is involved in T cell receptor signaling, as shown on the left of this slide. More important to the team at Corvus is ITK's involvement in the differentiation of normal naive helper T cells into helper T cell subsets known as Th1, Th2, and Th17.
Studies conducted in the early 2000s using genetic knockout mice demonstrated that ITK is required for the formation of Th2 and Th17 cells and the cytokines that they produce, such as IL-4, IL-5, IL-13, IL-17, and many others. These cytokines are involved in many inflammatory allergic diseases and are targets of many successful biologic medicines. Th1 cells were not affected in the knockout mice because Th1 cells express a redundant enzyme known as RLK, or resting lymphocyte kinase, also sometimes referred to as TXK. The gene knockout studies also showed that knockout of both RLK together with ITK results in complete immune dysfunction. You don't want that. So based on these studies and others, we set out to make a highly specific inhibitor of ITK that spares the other TEC family-related kinases, especially RLK. This would, in essence, be the pharmacologic equivalent of the genetic knockout.
One other point to make as shown on this slide. Recent work has shown that ITK also controls a switch from Th17 inflammatory cells to suppressive T regulatory cells. Blockade of ITK drives cell differentiation away from inflammatory Th17 cells to the suppressive T regulatory subset. This may be very important as it would be possible that this mechanism would lead to long-term disease remissions since T regulatory cells may persist for extended periods and suppress inflammation. The mechanism of action of soquelitinib is very different from other agents used to treat inflammatory or autoimmune diseases. In general, most of those agents work downstream to block one or two cytokines or cytokine receptors. soquelitinib has the potential to block multiple cytokines and signaling pathways affecting cellular functions. We were able to synthesize a highly specific inhibitor of ITK as shown on this slide.
The chemical structure is shown along with the specificity, biochemistry, and enzymology, which were just published in Drug Discovery, a Nature journal in December. Briefly, soquelitinib is a covalent drug that irreversibly and selectively binds ITK and none of the other kinases such as RLK, BTK, JAK3, and others. Also shown for comparison is ibrutinib, a BTK inhibitor that has been reported to bind to ITK. It does bind ITK very weakly; however, it also binds RLK and BTK very strongly, so it is not selective. The specificity of soquelitinib, limited tissue expression of ITK, and relatively rapid clearance of the drug from the body contributes to its anticipated safety profile. There is very little chance for off-target reactivity.
We have a very strong patent position for soquelitinib, including issued composition of matter patents with a term lasting until November 2037 in the U.S., not including the potential for patent term extensions. Several other patent applications covering methods of use have been filed. With that as background, let's now discuss the clinical trial and results, starting with the trial design. Eligible patients have met the Hanifin and Rajka criteria and have moderate to severe atopic dermatitis who have failed at least one prior systemic or topical therapy regimen. There are four cohorts that are sequentially enrolled. Sixteen subjects are enrolled in each cohort: four placebo and twelve actives. The complete study will evaluate sixteen placebo subjects and forty-eight subjects receiving different dosing regimen or schedule of active therapy for a total of sixty-four patients. The study is double-blind. Neither the patient nor the doctor know the treatment assignment.
The placebo and active tablets are indistinguishable. The main reason for blinding is to prevent any potential bias, especially with regard to efficacy evaluations. The company is not blinded, and we are able to evaluate the data as the study progresses. We wanted to maintain the ability to adjust or amend the trial based on available data as the study progressed since this is a novel agent with a mechanism of action not studied previously in this indication. Patients receive study drug or placebo for twenty-eight days, and then they are followed for an additional thirty days off of therapy for a total of fifty-eight days on study. We designed the study in this way to evaluate safety and efficacy while on the drug and to identify the possibility of persistent effects after the drug is discontinued.
The endpoints of the trial are safety and efficacy measured by the EASI score, eczema area and severity index, and IGA Investigator Global Assessment. Each of the cohorts examines a different dosing regimen. The four cohorts are 100 milligrams oral twice a day, 200 milligrams oral once a day, 200 milligrams oral twice a day, and 400 milligrams oral once a day. These doses were selected based on our experience in T cell lymphoma patients. We have shown that these doses result in significant or complete target occupancy. 200 milligrams twice a day is the dose we are evaluating in our ongoing Phase III registration lymphoma trial. The rationale for selecting these doses is shown on the next slide. We can measure the percent occupancy of soquelitinib in the ITK active site.
A single dose of 100 milligrams oral provides peak occupancy of around 80% 30 minutes after dosing and a trough occupancy of 40-50% 12 hours after dosing. Higher doses of 200 and 400 milligrams provide nearly complete target saturation on a continuous basis. This is a covalent drug. Therefore, plasma Cmax levels may be more important than AUC or area under the curve levels. This is an additional reason for the design of our dosing cohorts. It is likely to be unnecessary to completely occupy the target site continuously. Our initial dose of 100 milligrams twice a day would be expected to be active since as a significant target occupancy is seen. Of course, atopic dermatitis is much different than T cell lymphoma, although they both involve Th2 lymphocytes.
The next slide shows the characteristics of the 16 patients enrolled and treated in the first cohort. The placebo and active groups are shown. There are a few characteristics to point out. The mean baseline EASI score of 20.4 in the active group is slightly worse than the placebo 18.5. There is a high percentage of African American patients in both groups. Such patients are reported to have a worse prognosis. None of the patients in the active group received concomitant topical corticosteroids during the study period. One patient in the placebo did receive concomitant topical corticosteroids. All patients, except the one placebo patient, discontinued topical corticosteroids at least 27 days before dosing on the trial. One other point to make. The mean baseline EASI scores are somewhat lower than seen in earlier Phase I trials with Dupixent.
In those studies, mean baseline scores of 22-30 were seen. However, we believe our patient population is representative of today's real-world experience. For example, as reported by Silverberg in the journal Dermatologic Therapy in 2023, lower baseline EASI scores were associated with more recent start dates of clinical trials in atopic dermatitis, looking at trials from the period 2013-2020. Now let's move on to the efficacy results, which are shown in the table for both four weeks on treatment and following the additional 30 days off treatment or day 58. Let's first focus on the four-week data. Shown in the first two columns, the mean percent reduction of EASI score in the placebo group is 27.0% and is 55.9% for the active group, an absolute difference of 28.9%.
There are only 4 placebos and two reached EASI 50 scores. None reached EASI 75, none reached EASI 90, and none achieved IGA 0 or 1. In the active group, nine of 12 or 75% achieved EASI 50, three of 12 or 25% achieved EASI 75, and one of 12 or 8% achieved EASI 90. There were three of 12 or 25% in the active group who achieved IGA 0 or 1. Results at day 58 shown in the right two columns are of interest. The placebo group demonstrated a change in disease severity with a mean percent improvement in EASI score from baseline decreasing from 27.0 at day 28 to 19.1 at day 58, and only one patient remained an EASI 50.
In the active group, the mean percent change in EASI score improved to 69.1%, a 50-point difference compared to placebo. Improvement in the other efficacy scores was consistently observed: EASI 50 of 90% or 9 out of 10 patients, EASI 75 of 40% or 4 of 10 patients, and EASI 90 of 10% or 1 out of 10 patients. 3 of 10 patients achieved IGA 0 or 1. 2 patients did not have day 58 follow-up. One of those patients was the EASI 90 at day 28. The other patient was an EASI 13 at day 28. The next slide shows the kinetics of response. On the left side, which shows patients treated with soquelitinib, we begin to see improvement as early as day 8, with continued improvement over the duration of the study. The placebo is shown separately on the right side.
With small sample size, the standard error bars are wide, but we can see that there is very little change in the placebo over the course of the study. One other point about placebos, especially in light of some recent clinical trials with injectables for atopic dermatitis that have reported large treatment effects in placebo patients as a possible reason for study failures. There are numerous studies reported in the literature demonstrating that placebo treatment effects are much greater with injectables in contrast to oral medications where placebo effects are smaller. On the next slide, we compare our results to historical data with Dupixent. For this analysis, we are using data from the Phase I study of Dupixent published in the New England Journal of Medicine in 2014.
This was a dose escalation trial designed to find an optimum dose and then evaluated that dose in four-week and 12-week continuous treatment regimens. The optimum dose of Dupixent selected was 300 or 150 milligrams given subcutaneously on a weekly basis. On this slide, we compare soquelitinib to Dupixent four-week dosing. You can see that the results for soquelitinib and Dupixent in the placebo and active treatment groups are very similar. On the next slide, we compare our four-week treatment regimen followed by 30 days off treatment with four and 12 weeks of continuous Dupixent therapy. There is improvement in efficacy seen with longer duration of Dupixent treatment. The soquelitinib day 58 eight-week group appears similar to the Dupixent 12-week continuous treatment group.
The soquelitinib mean reduction in EASI score improves from 55.9% at four weeks to 69.1% at eight weeks, while the Dupixent mean reduction in EASI improves from 57.7% at four weeks to 74.0% at twelve weeks. Both soquelitinib and Dupixent also show increases in the percent of EASI 50 and EASI 75 patients and patients with IGA 0 or 1 at the later time period. Finally, on this slide, we show the data from the Phase III SOLO 1 and SOLO 2 registration trials for Dupixent in the last two columns on the far right. SOLO 1 and SOLO 2 were two separate but identical registration trials.
Again, it appears that the results are similar when you look at the soquelitinib eight-week data in the far right column of the black text compared to the SOLO 1 and SOLO 2 data in the far right column of the blue text. Both showed around 70% mean reduction in EASI, with soquelitinib patients receiving four weeks of active treatment compared to 16 weeks on therapy in SOLO 1 and SOLO 2. Now let's review the safety. As shown on this slide, there were no significant safety issues observed with soquelitinib. All the patients completed the 28 days of dosing. One patient reported grade one nausea. There was one patient who developed COVID-19 on day 28 of treatment. He had an uneventful recovery. No clinically significant laboratory abnormalities were seen.
The total current treatment experience with soquelitinib now involves over 100 patients with T cell lymphoma or atopic dermatitis, representing approximately 9,000 patient treatment days. In our lymphoma trial, some patients have been on therapy up to two years. Now let's look at the effects of soquelitinib on serum cytokines. We have been measuring about 20 different serum cytokines. We do see relationships between reductions from baseline in certain cytokines with improvement in EASI scores. Significant cytokine changes were seen for IL-5, IL-17, IL-31, IL-33, TSLP, and a trend for TARC in patients achieving an EASI fifty compared to patients that did not achieve EASI fifty. In the next slide, the cytokine findings in three placebo patients with available serum samples are compared with the soquelitinib-treated patients.
In these graphs, we show the cytokines that demonstrated the largest differences between soquelitinib responders and non-responders: TSLP, IL-17, IL-31, and IL-33. No significant treatment effects on cytokines were observed in the placebos, which are labeled PBO. Many cytokines are produced locally in the tissues and have very short half-lives in serum. IL-4, for example, has a plasma half-life of minutes. This makes assessment of some serum cytokine changes challenging. Similar relationships between EASI score improvement and expression of various inflammatory genes also were reported in the Phase I Dupixent trial published in the 2014 New England Journal of Medicine article. Now I would like to provide an update on results from Cohort II. As of December sixteenth, we have enrolled 12 patients in Cohort II, and patients are at various stages of follow-up. Some of the patients have reached the 28-day follow-up.
So far, we have seen no treatment-related adverse events. As you can see on this slide with the data as of December seventh, improvements in EASI scores are tracking very similar to that seen in the first cohort. Although very preliminary, the higher plasma Cmax of soquelitinib that is achieved with the higher once-per-day dosing of 200 milligrams may be slightly more effective. More data and follow-up are needed to confirm this. There are only three placebos, and they are not shown here because their follow-up is very short at this time. We expect to have more to say about the Cohort II data sometime early in twenty twenty-five. The next slide summarizes our understanding of the inflammatory pathways affected by soquelitinib compared to other agents.
As shown in the chart, soquelitinib blocks several Th2 cytokines like IL-4, IL-5, IL-13, and IL-31, and several TH17 cytokines such as IL-17, IL-21, and IL-22. soquelitinib also affects ILC2 cells, which are resident lymphoid populations present in skin, lung, and GI tract. ILC2s are known to have very high expression of ITK. Recent research has demonstrated that these cells play an important role in immune diseases such as atopic dermatitis, asthma, and colitis. As mentioned earlier, ITK controls the switch between TH17 cells and T regulatory suppressor cells. soquelitinib has been shown to enhance Treg expression, which could lead to persistent effects. To summarize, soquelitinib modulates cells responsible for production and control of many inflammatory cytokines and may restore immune balance by enhancing Tregs. Let me summarize the results from this trial so far. soquelitinib is an oral agent with a novel mechanism of action.
Safety has been demonstrated in lymphoma patients and now in atopic dermatitis. Including our T cell lymphoma trials, over 100 patients have now received soquelitinib, some for up to two years. Preliminary evidence of efficacy has been found at our initial dose of 100 milligrams twice a day given for 28 days. Responses appear to be durable. The safety, mechanism of action, and other properties suggest that soquelitinib could be an important new treatment for a broad range of immune diseases. We are continuing to optimize dose and schedule and expect further improvements with longer duration of therapy and/or modified dosing regimens. With that, I will now turn the call over to Dr. Albert Chiou to provide his perspective on the Cohort I data we have reported today and the overall opportunity for soquelitinib. Dr. Chiou ?
Thank you, Richard, and thanks for the opportunity to comment on the results of this study. So just briefly about me, I direct a clinical trials group where atopic dermatitis is a long-standing interest of mine. I've been involved as principal investigator or co-investigator on a number of industry and federally funded trials in this indication, including phase trials for Dupixent, lebrikizumab, upadacitinib, baricitinib, and I've been involved in the medical advisory boards for agents like abrocitinib. I also have a medical dermatology clinic with an emphasis on this disease and share in the collaborative care of more complex eczema patients with two similarly interested colleagues in my department. Atopic dermatitis is an important disease both because of its potential severe impact on quality of life and the fact that it's so common.
Th2 expression activation is a key driver of the condition, and this can result in significant disruption of quality of life through itch, infections, sleep disruption, and social and professional impediment. Most patients will be managed initially with topical steroids, which can be successful if the condition is more limited involvement and if there's good patient buy-in. When the condition is more severe or involves a large body surface area, we often look to systemic therapies to control the rash. Although there are now some relatively effective biologic therapies, these require injections and can have side effects like conjunctivitis or injection site reactions. Also, responses can be variable across individuals, reiterating the importance of having different agents that might work across patients with different immune phenotypes. There are also some approved targeted oral therapies, namely the JAK inhibitors, that are often quite effective.
However, the currently approved agents carry a class-wide black box warning that's quite significant, and this can often make for challenging conversations with patients who place high value in minimizing risks of treatment, as the box warning includes some heavy hitters like risk of blood clots or death. This means that dermatologists have to carefully assess the risk-benefit for each patient while trying to reach for an oral agent. Further, the JAKs also require regular blood monitoring because of their immunologic and hematologic effects, which does add a layer of burden to patients and their care teams. I'm overall very impressed with the early results reported with soquelitinib. The safety data look quite promising thus far, and the data so far provide meaningful early evidence of efficacy, especially with only a twenty-eight-day dosing regimen and a dose that has not yet been fully optimized.
I understand a number of my AD research colleagues at other institutions have had similar reactions to these preliminary results. I'm especially interested in the persistent efficacy and the possibility that the drug may be modifying the underlying biology of the disease. This would be very exciting if confirmed in future studies, as many of our targeted oral therapies, in particular, often result in a fairly rapid return of disease activity when we pause them, and of course, the fact that this is an oral medication is advantageous in itself since many patients are hesitant to embark on regimens of injectable therapies. At least in my practice, one of the first questions my patients ask when discussing next steps after topicals is whether there's a pill that's quite safe, so I'm always eager to learn about potential new additions to the armamentarium like this.
Finally, it's exciting to see a drug with a novel mechanism that appears to hit several points in the disease by blocking multiple cytokines, as our atopic dermatitis population does represent a heterogeneous mix of different immunologic profiles, which we see through the variable responses to our current targeted biologic therapies. I'm very happy to be part of this study and look forward to future results as the trial progresses. So over to you, Jim.
Thank you, Dr. Chiou. With that, I think we can now open the session to questions.
Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press the star followed by the one on your touch-tone phone. Questions will be taken in the order received. Should you wish to cancel your request, please press the star followed by the two.
If you are using a speakerphone, please lift the handset before pressing any keys. Once again, that is star one should you wish to ask a question. Your first question is from Aydin Huseynov from Ladenburg Thalmann. Your line is now open.
Good morning, everyone. Congratulations with these impressive results with such lower doses. So I've got a couple of questions. First, I want to ask, given the broad targeting of cytokines, when do you think these EASI scores may actually peak? Would it be sort of classical week 16 or earlier or later than then? Just curious about your thoughts on this.
Well, let me comment first, and then I'll toss that over to Dr. Chiou. But 28 days is a very short regimen. We deliberately picked that because we expected and wanted to see early responses because we do hit multiple cytokines in multiple pathways.
So we expected that we might have a more rapid onset. In terms of the optimum duration of therapy or how long the effects would last, the remitted effects, that's something we plan to study. In fact, we're already planning Phase II studies to look at that very question. Albert, do you have any comments on the rapidity and duration and so forth?
Yeah, you know it's tough to say with only a twenty-eight-day dosing regimen right now. You would really hope if we're seeing parallels to dupilumab, you know, two to three months to really see some optimal effect. But again, I think we are seeing some interesting effects here such as that longer durability. So I'm excited to see what turns out. I think it's too early to say right now.
Thank you. Appreciate that.
Given you saw the effects from such lower doses and you got sort of those dose-dependent responses, we saw some initial data from 200 mg QD. What are your expectations from the higher doses from 200 mg BID for 400 mg QD? I mean, it seems like you're already competing with Dupixent, but what would we expect from the higher doses here?
Thank you for that question. Let's not forget that we have a lot of experience with dosing in lymphoma patients where we've done careful monitoring of PK and occupancy and things like that and immunologic effects. And that certainly provides important information for our atopic dermatitis study. A hundred milligrams twice a day, as I showed on our slide, does give you 50%-80% occupancy. That's pretty good target occupancy with a covalent drug.
And we picked that because we thought that that could be sufficient. However, as shown on that slide, 200 and 400 pretty much fully saturate the target for a long period of time. We know that that's more important in lymphoma responses that you get full saturation. We also know that from some animal models. But the purpose of the design of this study was to do just that, to evaluate the safety and to determine what dose would give us the maximum or a good effect. If I had to guess, based on what we know from lymphoma, I would say 200 milligrams BID is probably going to be your best dose. But that's just based on our lymphoma work. Atopic dermatitis is not lymphoma. But I would guess that we're creeping up on what would be the best dose. Now, duration of therapy is a really important question.
I don't think we're going to have to treat for 16 weeks or 12 weeks. I think that we might be able to treat for a much shorter period of time, which would be a tremendous advantage. I also think that it's possible, and like Dr. Chiou maybe to comment on this, that perhaps you use this drug intermittently. Patients go in remission. If they recur, if and when they recur, maybe you treat them again when their disease flares or whatever. So I think that we're in a new paradigm here, possibly, with an oral safe drug that works by a different mechanism of action where you don't have to continuously block a cytokine that's being produced 24 hours, seven days a week, and where there's feedback mechanisms and increases in serum cytokines and things like that.
So this is a really new paradigm, I think, in the treatment of not only atopic dermatitis but potentially other immune diseases. Dr. Chiou?
Yeah, I'd just say that our patients oftentimes have many different goals for atopic dermatitis. I'd say a lot of them just want a lot of predictability and to know that they can keep the disease well controlled. And so a continuous dosing for them is very reasonable, and ongoing therapy is attractive. There are some folks who like the idea of being able to take a break and not expect a bad rebound flare or have something occur where all of a sudden they're back worse than when they began. And so I think having a medication where you're seeing potentially persistent benefit a month after you stop it, I think for some patients that's something that's very attractive.
Okay. Thank you. Appreciate it.
I think we can take the next question.
Yes. Thank you. The next question is from Jeff Jones from Oppenheimer. Your line is now open.
Good morning, guys, and really congrats on the data. It's really impressive. The question for you that goes to this durability of response, and you were putting up the Dupi data. And I'm wondering on whether we should be really focused on that eight-week-to-eight-week comparison where Dupi 's being given continuously or the better comparison would be something like week four because you guys stopped dosing after 28 days. And so how should we be thinking about the comparison there in the most relevant data, 28 days or rather four weeks versus eight weeks?
So Jeff, I think they're both important.
I mean, we predicted, we knew ahead of time based on published work by others and our own work in the laboratory that there is this effect on suppressor T cells. And so both are important. Do you have an effect in four weeks, and is there long-term tolerance of some sort? But I think the first thing I would do is look at the four-week Dupi data compared to ours. Now, obviously, that's a larger data set. We're only talking about 12 patients here who are treated. We understand that. It's nice to see that we're tracking similarly in our cohort two. So that's comforting. So I mean, I would eventually initially focus on the four-week data. That's why we showed that slide. But the basic science tells us that there could be a different mechanism and a different effect here that could be more prolonged.
I think, and Albert knows this better than I do, when you stop Dupixent or some of these other drugs, your disease comes back. And we're hoping that we can have an advantage there. Albert?
Yeah, no, I think it's a good question. You're right. The AD does usually come back after you stop Dupixent. It can have some lasting benefit for a number of months afterwards because it is a biologic therapy. I think it is just unique again to see this type of durability with an oral medication. Again, when you think about it, it's almost like an unfair comparison because in those other studies, you have Dupixent continuously dosed, and you just have 28 days of dosing here. So I think it'd be really interesting to see what happens ultimately in later phases if you give this medication for longer periods.
Okay.
Then the other question I was just going to ask, and maybe best for Albert here, in terms of the lack of placebo signal that we saw at the EASI 75 and what was commented on and what is perhaps a little less severe population than what we've seen in some of the early Dupixent trials, should that be a flag to us, or is that more of a small numbers thing?
So Jeff, I would say that the lower baseline EASI scores, if anything, make it more challenging for us and other clinical trials to show a benefit. Just based on the arithmetic, a small change in a lower number is a bigger percentage change. But the reality is that these are the types of patients that are going on studies now. So I don't think I would worry about that.
The bigger issue, I think this is going to be something to look at, is there are not that many studies using oral agents. And there are a lot of studies with injectables. And it is well known in the literature, not specifically for atopic dermatitis, but it's known in arthritis studies and pain studies and various other areas of medicine. Weight loss drugs, for example, would be another one where the placebo therapeutic effects of an oral agent are typically smaller compared to injectables. And I think that most people could understand why it seems reasonable that in injectables, people would assume it's a more powerful therapy, even though it may not be. So I don't know if I've answered. Albert, do you have any comments on that?
Yeah, I think if you take a look at that figure where you actually see the placebo group on and off treatment in terms of the curve, honestly, what jumps out to me is that really wide confidence interval at day 28 and day 58. I just think with only four patients, we're really early on. I think the behavior of the placebo group is not jumping out at me as anything too unusual. Just when you have small numbers like this, you'll see a lot of variation. A single patient can really drive some of these curves when you're dealing with numbers as small.
Okay. And then just a quick last question. You showed a bunch of cytokine data. Did you look at IL-13, and was there an effect there?
We didn't see effects there.
But again, the problem with some of these we're looking at the serum is that some of these cytokines have a very short half-life and also are complex. So the body is very smart. It actually has circulating decoy receptors that complex the cytokines and make them hard to detect. So I think the absence of a signal is hard to make a conclusion about. The presence of a signal, you can conclude something. But some of these cytokines, and I think the slide is back up now, for example, IL-31, we see a big difference in responder-non-responder. IL-31, of course, is the itch cytokine. IL-33 is very interesting to us. That drives ILC2s. We see IL-5, of course. IL-17, very interesting. That's a pretty big difference we see there. I mean, the p-value there is three zeros in front of it. So some of these things are pretty interesting.
And you don't see those changes. You don't see those changes in the placebo, which is, again, gives us confidence in the activity of the active versus the placebo. So no, but the other ones like IL-4, we weren't able to detect changes, but that does not mean it doesn't happen. I would expect IL-4 to change because we see that in vitro right away. When we do those experiments in the lab, you see big effects on IL-4. But the problem in a clinical trial is the IL-4 survival. Intravenous IL-4 has a half-life in 19 minutes. And so timing is everything. Anyway, all right.
Maybe we can take another question. Any other?
Thank you. Your next question is from Li Watsek from Cantor. Your line is now open. Hey, good morning. Congrats on the data. Maybe just a couple from me. Just follow up on the baseline.
Can you talk a little bit about the differences between drug and placebo groups that you discussed earlier, especially around race and prior treatment, which seem to favor the drug arm? And the second is, Rich, I wonder if you can clarify if there were any rescue medicines used either during the four-week treatment period or the follow-up.
Okay. Thank you, Lee. No rescue medications were given to any patients. That's the answer to that question. With regard to the baseline characteristics of the patients, I would say, if anything, the soquelitinib patients were worse. They did have a slightly higher baseline EASI score. None of them were on topical corticosteroids, discontinued almost a month before they came on the study. There was one of the four placebos. Of course, again, we're talking about very small numbers here. We have a high proportion of African-American patients in both placebo and soquelitinib.
So hard to say. I don't think that there's anything that jumps out to say that the placebo is different here, very different from the soquelitinib treatment. If anything, I would say the soquelitinib perhaps is slightly worse, but that would be a very soft call. Albert, do you have any comments on that?
Yeah, I'd say just looking at the numbers for just the N4 cohort one, I think actually pretty comparable. My eyes really jumped to baseline EASI, baseline IGA, and I think for the few patients I've enrolled so far, it's actually really nicely comparable between the two. I agree. It doesn't seem like any particular concerns with randomization looking at any of the other baseline characteristics, especially in keeping in mind four patients in that placebo arm so far. Yeah.
Okay. Any other? Let's maybe take next question.
Thank you.
Your next question is from Graig Suvannavejh from Mizuho Securities. Your line is now open.
Thank you. Good morning. Congrats on the data. Thanks for taking my questions. I've got two. Maybe first for Dr. Chiou. Thanks for your feedback. Very helpful. The question is based on this data at this dose and maybe with a view that the 200-milligram dose might be similar, if not even slightly a bit better. If this drug were available in your hands to use in patients, how would you use this particular drug? So just kind of bigger picture on kind of how you would position this product relative to others. And then maybe a question back for Richard with respect to this data.
Can you just remind me, given what you're seeing in atopic dermatitis, what next other indications do you think make the most sense in terms of looking further with soquelitinib? Thank you.
Albert, I'll let you go first.
Great. Yeah. So
I'm just kind of thinking back to our experience with the JAK inhibitors. A lot of how we use these oral medications for control of atopic dermatitis is largely driven by the safety profile. I think that's why I'm pretty excited to see kind of that at least early emerging safety data here.
You could imagine that if patients are, again, that profile or patients will be looking for a lot more predictability, control, essentially start at whatever a higher dose is, get you clear if the safety profile continues to be this positive, and eventually just gradually down-titrate to whatever the lowest amount is that'll keep you from having recurrent flares and kind of add that predictability to your life. And oftentimes, we just love to cruise at that altitude, essentially. There are a lot of patients, if there is any safety signal that comes in, that will accept some degree of risk in order to really be able to maintain clearance. But again, this will really be driven by that AE profile that emerges. If it becomes more significant, you'd want to start low and then go high if you're forced to.
That's kind of how we do it with the JAK inhibitors, but the safety profile is extremely good. Just get folks clear and then go down, and then, yeah, I think a lot of folks, again, that needle phobia and with biologics, it'd just be really nice to have this as an option to talk to folks about. Just the first question always is, "All right, so after the cream, is there a pill?" and would love to be able to talk to them about a pill without such a large kind of safety conversation as what we currently have in our hands.
Okay, and Graig, you asked me about next steps, so obviously, we want to try to finish the current trial, get as much information as we can on dosing and cytokines and all that sort of stuff.
We are on track to complete enrollment of the second cohort by Christmas, and then we'll move on to cohort three and four. We're already starting to think about Phase II trial, which, as I mentioned, in atopic dermatitis, which, as I mentioned, would explore maybe one or two doses and perhaps different durations of therapy. In terms of next disease, we're interested in asthma now. Atopic dermatitis patients frequently have asthma as a concomitant problem, children and adults. So they go together very often. The mechanisms of disease pathophysiologies are obviously somewhat related. We have a lot of laboratory data showing activity in various asthma models. So asthma would be a next step. We are also considering other more serious diseases, more life-threatening diseases. As you know, we had a recent paper on scleroderma, systemic sclerosis, mouse model, where the drug seems very active in that model.
So there's an opportunity there to move into a patient population where there's a serious unmet need. So those would be our next steps. Phase II AD, asthma, perhaps scleroderma, and a lot of other things. At JP Morgan, I'll be talking about another disease that we're quite interested in. In fact, I think it was posted already on ClinicalTrials.gov, but I'll say more about that at the JP Morgan conference. Next question.
Do we have any other questions? Oh.
Yes. The next question is from Roger Song from Jefferies. Your line is now open.
Great. Thanks for taking the question and congrats for the data. Maybe one question related to the positioning.
Given this is an oral drug and potentially can be a bridging between the topical and biologic, just curious, you may have a small n, but any analysis you have seen for those patients with prior systemic or biologics versus a new patient in your Phase II, do you consider to separate those two populations in order to tease out the signal for soquelitinib to be able to position in that specific population? Thank you.
Let me see if I understand your question. I think based on Dr. Chiou's comments earlier and what we've been saying is that this is possibly the go-to right after failure of a topical corticosteroid before you would go to an injectable. In terms of if you're asking Roger, of the patients we described here this morning, there were only two who had prior Dupixent.
One is the patient who I mentioned got COVID, and the other was a placebo. So really can't say about whether prior Dupixent or anything like that matters because we just don't have enough information. From a mechanistic standpoint, I would see no reason, no scientific reason to think that exposure to a prior biologic would somehow affect the outcome. Albert.
Yeah. Speaking more personally as a dermatologist and kind of what I'd love to see is I'd love to see how this medication performs in patients who've failed prior biologics. With the biologics, kind of our thinking is that these are oftentimes quite positive safety profiles, but they are so targeted that if the patient has a different immune phenotype and you're not right on target, that's why you get these variable responses with the biologics.
If you have something that hits multiple Th2 cytokines like this oral medication looks like it does, you might be able to capture a lot more of these patients and offer that higher surety of a response to the patients. So I personally would love to see how these targeted biologic failure patients do because I think the hope would be that they continue to do really well even compared to the naive treatment patients.
Thanks.
Okay. Are there any more? Okay. I think that concludes the Q&A session. I want to thank Dr. Chiou for participating in our session today. I want to thank all our investigators and patients, of course. And I want to thank you all for joining the call this morning. We look forward to updating you on our progress as the study progresses. Thank you very much.
Thank you.
Ladies and gentlemen, the conference has now ended. Thank you all for joining. You may all disconnect your line.