Corvus Pharmaceuticals, Inc. Q1 FY2026 Earnings Call

Good morning, everyone. Thank you for standing by and welcome to the Corvus Pharmaceuticals Conference Call. At this time, all participants are in 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 Zach Kubo of Real Chemistry. Please go ahead, sir.

Thank you, Operator, and good morning, everyone. Thanks for joining us today on the call. This conference call is being webcast with presentation slides. We encourage participants to join the webcast in order to view the slides. You can find the link to join the webcast on the Investor Relations homepage of the Corvus website. On the call today are Dr. Richard Miller, Chief Executive Officer, Lai Flea, Chief Financial Officer, Jeff Fartera, Chief Business Officer, Dr. Ben Jones, Senior Vice President, Pharmaceutical Development, and Dr. Suresh Mahabashem, Vice President, Clinical Development. The executive team will open the call with some prepared remarks, followed by a question and answer period. I would like to remind everyone that comments made by management today and answers to questions will include forward-looking statements. Forward-looking statements are based on estimates and assumptions as of today and are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied by those statements, including the risks and uncertainties described in Corvus' quarterly report on Form 10-Q for the quarter ended September 30, 2025, and other filings the company makes with the SEC from time to time. The company undertakes no obligation to publicly update or revise any forward-looking statements, except as required by law. With that, I'd like to turn the call over to Richard Miller.

Thank you, and good morning, everyone. We are very eager today to present the results from our Phase I clinical trial with socolitinib in atopic dermatitis. The data reinforced that socolitinib is a first-in-class oral drug that represents a potential significant breakthrough for the treatment of atopic dermatitis and other immune diseases. I've had the privilege of being involved in the discovery and development of two pioneering medicines, rituxan, an anti-CD20 antibody widely used for the treatment of lymphomas and immune diseases, and ibrutinib, a BTK inhibitor also widely used for the treatment of lymphomas and more recently expanding indications into immune diseases. It is my belief that selective inhibition of ITK may be following a parallel path and also may now find its place along with these breakthroughs in medicine. Today, I would like to start with some background on ITK and socolitinib, and then we will cover our safety and efficacy data from all the cohorts and placebo. We will focus mostly on new data from our cohort four, as well as longer follow-up from cohort three and our emerging biomarker data. We will review our data in patients who receive prior systemic therapies. And we will discuss our go-forward plans, including the opportunity for socolitinib to address a range of clinical indications. Before getting into more details on the background and clinical data, let me summarize the key takeaways as shown on this slide. Cohort 4 results show that socolitinib could become a leading therapy for atopic dermatitis, and it is oral. First, it confirmed positive clinical results in the trial. It appears that socolitinib is safe and effective therapy for atopic dermatitis. EZ75, EZ90, and IgA01 were achieved 75%, 25%, and 33% of patients, respectively. The mean percent reduction in the EZ score is 72% at eight weeks of treatment. Second, we have shown deeper, durable responses. Extending the treatment to eight weeks from four weeks in cohort four is safe and leads to a deepening of response. Third, responses are durable and with continued reduction of EZ scores post-treatment, including for longer follow-up in cohort three. Fourth, soqualitinib is an active drug in patients who have received prior systemic therapies with similar efficacy in systemic treatment naïve or experienced patients. And fifth, biomarkers have been identified that support the novel mechanism of action with ITK inhibition that leads to an immune system rebalancing. With the additional information that is emerging, both from the clinic and our biomarker analysis, such as induction of Tregs, we believe that socolitinib's novel mechanism and safety will allow for its utility in diverse indications in immune inflammatory diseases and in cancer. Let's get started with the next slide. ITK, or interleukin-2-inducible T-cell kinase, plays a crucial role in the differentiation of naive helper T-cells into more specialized cells known as Th1, Th2, and Th17. Gene knockout experiments in mice done many years ago show that knocking out ITK results in the inability to form Th2 and Th17 cells. These pro-inflammatory cells produce many inflammatory cytokines, such as IL-4, 5, 13, 17, and others. So, blockade of these cells inhibits production of a range of inflammatory cytokines. Th1 cells possess a redundant enzyme known as RLK, or resting lymphocyte kinase. So, ITK inhibition does not interfere with their function. The Th1 cell is crucial for anti-tumor immuting and fighting infection, especially from viruses. This suggests that selective ITK inhibition would not lead to immunosuppression. More recently, another critical function of ITK was discovered, as shown on this slide. ITK controls a switch between Th17 and suppressive T regulatory cells. Independent investigators have shown that using either gene knockout of ITK or blockade of ITK using socolitinib results in a switch from Th17 to the Treg cells. This is an exciting result, as the induction of Tregs has been a highly desired treatment strategy for control of autoimmune diseases. We will be talking more about Tregs later. Our strategy was to make a drug that would inhibit ITK selectively. If that was possible, then one could potentially reduce inflammation and autoimmunity without causing immunosuppression. This would require a drug that was very specific for ITK and especially SPARE's RLK. The realization of this critical feature and the synthesis of such a pharmaceutically acceptable compound had never been accomplished before. Based on our experience with BTK and kinase inhibitors, we were able to do just that. This slide shows the exquisite specificity of socolitinib for ITK as shown on the kinase dendrograms. Here we compare to ibrutinib, which binds several tech family-related kinases, including ITK. Socolitinib is an oral, covalent, irreversible drug that only binds to ITK. The specificity of binding and the dissociation constants are shown in the table. A low number means strong binding. Soqualitinib binds ITK at low nanomolar concentrations. The details of this work were published last year in the Nature Partner Journal Drug Discovery. Now a word about specificity, since it has important clinical implications. In the case of ITK and socolitinib, we have a target that has limited tissue distribution, T-cells and NK-cells, and we have a drug that is very specific for that target. The confluence of limited tissue distribution and specificity of the drug portend for safety since potential off-target effects are minimized. So, these two attributes contribute to the therapeutic index of socolitinib. Number one, the drug-specific binding. Number two, the target's limited tissue distribution. We first initiated clinical development of socolitinib in T-cell lymphoma. In December, we reported final results of our Phase I 1b study in an oral presentation at the annual meeting of the American Society of Hematology. and we are currently enrolling a registration phase three trial in relapsed peripheral T-cell lymphoma. The evaluation of socolitinib for T-cell lymphoma has the following rationale. Completely unmet need for better therapies. Ability to move quickly into the clinic to obtain safety, efficacy, PK, and effects on normal immune cells and function. Foundation for work in immune diseases, since T-cell lymphomas involve Th2 lymphocytes, also commonly involve the skin. The disease is often associated with autoimmune manifestations. An example is shown on this slide. Here are two patients from our Phase I T-cell lymphoma trial with cutaneous involvement. These patients had massive disease burdens that responded, one complete remission and one partial remission, to monotherapy socolitinib and they continued on treatment for two years, the maximum duration allowed under the protocol. As we were advancing in the clinic in lymphoma, we were also evaluating the potential for socolitinib in a range of immune diseases. Briefly, we found robust activity with the drug in many preclinical models, including asthma, pulmonary fibrosis, psoriasis, atopic dermatitis, inflammatory bowel disease, and others. An overview of these data are shown on this slide and involve areas of dermatology, pulmonology, rheumatology, and gastroenterology. Moreover, in experiments looking at socolitinib in human cells, both in vitro and in vivo, from our lymphoma patients, we confirmed the immunologic effects. As shown here, we found that socolitinib inhibits the production of IL-4, 5, 13 from normal T cells, but not interferon gamma because that is a Th1 cytokine. Similarly, looking at malignant cesary or Th2 tumor cells on the right, we also see reductions of these cytokines, including TARC. On the bottom of the slide, we show studies conducted on the blood from one of the lymphoma patients. These studies show the expected in vivo changes in Th1, Th17, and Th2. Note the profound reduction in IL-5 and eosinophils in this treated lymphoma patient. With this background, we initiated clinical trials in atopic dermatitis for several reasons. First, it is primarily a Th2 disease, but also involves Th17 and other cell types. Second, it involves the skin, similar to T-cell lymphomas. Third, it is a significant commercial opportunity with a need for safe and more effective oral therapies. This slide summarizes the market opportunity. Briefly, there are over 3 million patients with moderate to severe disease, and currently only a fraction are receiving therapy. Current therapies are mainly injectables, require continuous therapy, and or have troubling side effects. JAK inhibitors carry a black box warning. Let's move into our clinical trial on atopic dermatitis, or AD. This slide shows the clinical trial design. Patients with moderate to severe AD were eligible if they had failed at least one prior topical or systemic therapy. They were not require to have responded to the prior systemic therapy. This is in contrast to most other clinical trials where these unfavorable patients are not eligible. There were four cohorts evaluated sequentially. The study was placebo-controlled and blinded. Placebo controls are critically important in AD studies, especially with novel agents. The patient and doctor were unaware of the treatment assignment. The company was not blinded. For cohorts 1 to 3, 16 patients in each cohort were randomized to receive active or placebo at a 3 to 1 ratio, 12 active and 4 placebo. The treatment duration was 28 days with an additional 30-day follow-up off of therapy. Concomitant topical steroids were not permitted. The cohorts evaluated doses of 100 mg BID, 200 mg QD, and 200 mg BID. The doses were selected based on our experience in lymphomas, where a 200 mg dose was found to produce maximum target occupancy. 200 milligrams BID is the dose being tested in our phase 3 lymphoma trial. BID dosing was evaluated because we have shown that ITK protein turnover has a half-life of about 12 hours. Although socolitinib has a plasma half-life of a few hours, its pharmacodynamic effect is much longer because it is irreversibly bound to the target. We plan to evaluate other once-per-day dosing regimens in future trials, since it is not likely that one needs complete target occupancy continuously. As we discussed a few months ago, based on the promising findings from the initial three cohorts, we amended our protocol and designed a new Cohort 4 that had some key differences from Cohort 1 to 3. Cohort 4 was a prospectively defined clinical trial intended to corroborate and extend the results from cohort 1 to 3. The key differences were, one, 24 patients enrolled using a one-to-one randomization of active versus placebo, and number two, the treatment period was extended to eight weeks from four weeks with 30-day follow-up post-treatment. Socolitinib dose was 200 milligrams BID, same dose as Cohort 3. The one-to-one randomization was done to further strengthen our conclusions. This is especially important in atopic dermatitis, where efficacy endpoints have some degree of subjectivity. The entire study was conducted in the United States at 17 centers. Here are the baseline patient characteristics for the four cohorts. A total of 72 patients were enrolled across all the cohorts, 48 active, 24 placebo. The data for the cohort four patients is shown on the right. This cohort is very similar to cohort three. Age, proportion of African Americans, prior systemic therapy, and mean baseline EASY are very similar. The arms are well balanced. If anything, placebo is more favorable. Fifty percent of patients in cohort four had received prior systemic therapies. Let me review the efficacy data for cohorts one to three before moving to cohort four. This data has been presented previously, but it sets the stage for our cohort 4 data. As you can see, we find better efficacy in cohort 3, the 200 milligram BID dose, with mean percent reduction in EZ score of 64.8% compared to placebo of 34.4% at 28 days. The EZ 75 is 50%. One patient was an EZ 90. No placebo achieved EZ75, which is likely due to the short treatment duration of only 28 days, and our patient population is more unfavorable than most studies reported in the literature. Here are kinetics of response for cohorts 1 to 3. Cohort 3 shows a more rapid and deeper reduction in EZ scores compared to cohorts 1 and 2. The curves are continuously decreasing at day 28. This suggested to us that longer treatment duration could lead to deepening of response. Also, the responses persisted beyond the 28-day treatment period. For most other treatments, once treatment is discontinued, one sees a return of disease within a few weeks for many patients. This slide shows new data from Cohort 3, where the remission duration has been more systematically examined by amendment to the protocol, which provided for longer, blinded follow-up. Responses were maintained or slightly improved out to 118 days, an additional three months without therapy. Our hypothesis was that the induction of T-regulatory cells by socolitinib could be responsible for this remission, as we have seen in preclinical experiments. Indeed, we found an increase in circulating Treg cells in cohort 3 patients, but not in cohort 1, 2, and placebo. These cells are functional Tregs that are FOXP3 positive, CD25 high, CD4, and CD45 positive. It is remarkable to find these cells, as they are usually very rare in the blood, as they are trafficking to sites of disease. It is likely that these cells would be even more abundant in the involved skin sites of disease, as we have seen in animal models. Our conclusion from these results is that we may be inducing Tregs that contribute to durable suppression of inflammation and sustained disease remission. By comparison, here are published results from abracitinib, Sibinko, Pfizer's JAK inhibitor from their phase 2b study. This study followed patients beyond the 12-week treatment period. Shown here are the response curves at the various doses evaluated. The two bottom curves are the approved doses of 100 milligram and 200 milligram QD. Note the rapid rebound in disease that starts as soon as one week after stopping therapy, week 13. Other agents, including Dupixent, Renvoke, and some of the recent novel agents have similar findings. We have not seen this phenomenon. I also want to show some of our data on itch as reported using the PPNRS scale. This is a patient-reported outcome. This slide shows the data for Cohort 3 compared to placebo. It does appear that we have a significant effect on itch. We also show the frequency of a four-point change in the PPNRS scale. These are changes that are considered to be very clinically meaningful by regulatory authorities. Since high PPNRS was not an eligibility criteria, not all patients could reach the four-point threshold. Cohort 4 data is not yet available. Overall, our conclusions from Cohort 1 to 3 were that soquilitinib appears to be safe and effective compared to placebo with a 28-day treatment regimen and disease remissions are durable. Now let's look at cohort four results on slide 19. Here is the eight-week efficacy data for cohort four. The mean percent reduction in easy is 72% versus 40% for placebo. This was our predefined endpoint. The p-value is 0.035. 75% of patients achieved easy 75, 25% easy 90, and 33% IgA01. 11 of the 12 treated patients achieve EZ50, 92%. Two placebo patients achieved EZ75. On this slide, we show EZ75 for placebo of 2 of 10, or 20%. Two additional placebo patients were non-compliant and missed the day 56 evaluation, and on later evaluations never achieved EZ75, which would make the proportion 2 out of 12, or 17%. Two placebos required rescue medications due to disease flares versus none in the active group. Our conclusion from these data are that socolitinib is superior to placebo in every efficacy endpoint evaluated. Here are the response curves for cohort four. This is very clear data with the separation of the curves seen at the first clinic visit, day 15, and continuous separation from placebo at day 28, which further increases out to day 56 without a plateau and a steady downward slope. As noted earlier, the day 56 p-value, 0.035. We see a continuation in disease control in the post-treatment 30-day follow-up period out to day 86. These data confirm our hypothesis from cohorts 1 to 3, which is that extending the treatment duration would deepen responses. We allowed patients who had received prior systemic therapies in our study. Our hypothesis was that resistance mechanisms to other therapies would not affect the activity of socolitinib. This slide shows the prior systemic therapy experience in cohorts one through four of our trial. 35% of all patients had prior therapies, as shown on this slide, 50% in Cohort 4. Not surprisingly, Dupixin was the most commonly used agent, followed by JAK inhibitors. Some patients received multiple prior therapies. Some patients were resistant to their last systemic therapy. That is not responsive to treatment. Now let's look at our outcomes in patients with prior systemic therapies. On the left side of this slide, we show the response curves for all socolitinib-treated patients and all placebos, cohorts 1 through 4. The efficacy results in all treated patients is strong, with a p-value of 0.003 at day 28, which includes all the patients in the study. On the right, we show the response curves for those patients with prior systemic therapy. The separation of curves is very clear in both cases. The curves are very similar for patients receiving socolitinib, indicating that socolitinib is not affected by prior systemic therapy experience. Note that placebo patients who receive prior therapies do worse, indicating that prior systemic therapy is an unfavorable characteristic. This results in even greater separation of the curve from the so-called itinib arm. In the next slide, we show a similar analysis for patients in cohort 3 and 4 since they both received the same 200 milligram BID dose. On the left, all patients treated at the 200-milligram BID dose. On the right, those patients who received prior therapies. We utilize the same placebo groups as noted earlier for comparison. We see clear separation of the curves with wider separation in the patients with prior therapy. Again, the socolitinib curves are nearly identical, indicating that the treatment effect is maintained in both treatment-naive and experienced patients. On the next slide, here are all the curves together on one plot for cohort 3 and 4, just to highlight that the socolitinib curves are nearly identical for both prior treatment-naive or experienced. Although not shown, the same is true for the curves with all the patients cohort 1 to 4. Turning back to the patients that were resistant to their last systemic therapy, we were able to establish confirmation of treatment resistance in at least six patients who were not responding to their prior therapy as they came on our study. These patients would be excluded from most clinical trials, which either excludes patients with prior systemic therapy or requires patients to be responsive to that therapy. All of our patients were in cohorts three and four and included four active and two placebo patients. As shown on this slide, the two placebos had disease flares requiring rescue medications And three of the four soqualitinib-treated patients improved, with two achieving easy 90s. One patient had a 27% reduction. One patient did not respond to soqualitinib. This, by the way, was the only patient out of the 12 that did not achieve an easy 50. Our conclusions are that socolitinib is active in patients who have received prior systemic therapies with outcomes no different than naive patients, despite these patients having more unfavorable disease. Responses are observed in patients who are refractory to their prior systemic therapy. This supports our hypothesis regarding the novel mechanism for socolitinib and the lack of resistance due to prior therapy experience. Here is a summary of the efficacy data for all four cohorts, looking at EZ 75, 90, and IGA 01. Cohort 4 confirms and extends the efficacy of Cohort 3 with larger sample size and one-to-one randomization. 75% of socolitin-treated patients achieved EZ-75, 25% achieved EZ-90, and 33% are IgA-01. I should note, one additional patient was an EZ-74, a near miss. Two placebos achieved EZ-75. No placebo achieved EZ-90. It is worth noting that the two placebos that achieved EZ75 were both subjects with no prior systemic therapy. None of seven placebos with prior therapy experience achieved EZ75 compared to an EZ75 seen in three of five actives who received prior therapy. Now let's turn to safety on the next two slides. No new safety signals were seen in cohort four with the longer eight-week treatment duration. Reported AEs are similar in both placebo and active groups. No significant lab abnormalities were observed. On the next slide we show AEs of special interest. There are no hepatic abnormalities, no changes in liver function tests. Infections were similar and treated in placebo. We do not have the problems of conjunctivitis or injection site reactions, which are not only troublesome to patients, but also confound trial blinding. With a novel mechanism of action of socolitinib, we expect it to identify new and different biomarkers, and we are beginning to uncover these properties. A detailed description of these is beyond the scope of today's discussion, but we intend to present some of these data at the upcoming American Academy of Dermatology and Society of Investigative Dermatology meetings over the coming months. For now, this slide shows the effects on TH2s and serum cytokines. On the left, we show serum IL-4 levels from cohorts 1 through 4 and placebo. IL-4 levels dropped in cohort three and four and this drop occurs relatively late. The reduction is sustained and continues beyond the end of therapy in both cohorts three and four, consistent with our findings of prolonged efficacy. The reduction is dramatic out to day 86 for cohort four. Next we show serum IL-5 for cohorts 1 to 3. Cohort 4 results are in process. Each dot is a patient where serum IL-5 levels at baseline and on treatment are measured. Cohort 3 patients have the most reduction in IL-5 levels compared to cohorts 1 and 2, and these changes are seen as early as day 8. IL-5 in placebo patients is not affected. Interleukin-5 is a cytokine primarily produced by T cells and ILC2 cells, innate lymphoid cells. That is crucial for the growth, differentiation, activation, and survival of eosinophils. IL-5 plays a key role in allergic inflammation, particularly in asthma. IL-5 binds to its receptor and signals through STAT1, STAT3, and STAT5. Our findings indicate that changes in serum IL-5 levels occur early relative to IL-4, which occurs later. Next, we show the effects on Th2 cells. In six patients analyzed so far using single-cell RNA-seq in cohorts 1 and 2, we see a strong trend indicating a reduction in Th2 cells compared to baseline. This was found in five of six treated patients with socolitinib and not in any placebos examined so far. We are building on this and carefully analyzing cell types and gene expression in cohorts three and four using single cell RNA-seq. On the right side of this slide, we show early findings looking at serum IL-17 and TARC, which are both reduced compared to placebo. IL-17 is of particular interest to us since it is a product of Th17 cells. It is involved in atopic dermatitis, and it signals through STAT3. We are finding many other indicators supporting our mechanism of action, including effects on JAK-STAT signaling involving JAK1, JAK2, TIK2, STAT1, 3, and 6. All of this is suggesting that socolitinib will affect multiple cytokines and cellular functions involved in inflammation. We have just submitted an abstract on these results for the SID meeting, which occurs in May. Now let's compare our results to other agents. Here we show the endpoints of EZ75 and IgA01 for approved biologics and a JAK inhibitor, along with socolitinib. As you can see from this slide, our data at four and eight weeks for cohorts three and four are competitive with other approved agents at 16 weeks, including JAK inhibitors. We have a sicker patient population. We believe the results obtained so far for soquilitinib place it among the most active agents, oral or injectable, approved or under development for AD. Now I would like to discuss our upcoming plans. With the data shown today, we are very well poised to initiate our Phase II randomized placebo-controlled trial in AD as shown on this slide. The trial is planned to enroll 200 patients with moderate to severe disease randomized into one of four cohorts with 50 patients in each cohort. Doses of 200 mg QD, 200 mg BID, and 400 mg QD will be examined along with placebo. The treatment duration is 12 weeks with an off-treatment follow-up period. The primary endpoint is median reduction in EASY at 12 weeks, a typical endpoint for phase 2 studies in AD. This will be an international study. We plan to open this trial very soon in Q1-2026. On this slide, we compare the effects of socolitinib to other approved agents. Soquilitinib affects multiple cytokines in cell types, including IL-4, 5, 17, 31, and many others. It also affects Tregs and ILC2s. This is very different than the mechanisms described for other agents. Given these properties, the therapeutic opportunities in the I&I space are very broad, and they include TH2-mediated diseases, TH17-mediated diseases, IL-5-driven or allergic diseases, and fibrotic diseases. Recently, in collaboration with Dr. Yannick Alenor at INSERM in Paris, we published an article on the activity of socolidinib in mouse models of pulmonary fibrosis, including a transgenic model of systemic sclerosis. This paper has just appeared in the journal Arthritis Research and Therapy. The next slide summarizes the large and growing market opportunity in the INI space. As you can see from the slide, the market is anticipated to grow to $170 billion by 2030, with oral agents expected to gain an increasing proportion, which is still only a small fraction with the potential for significant growth. Let me summarize our findings to date and go forward plans. is first-in-class selective ITK inhibitor with a novel mechanism of action that appears well-suited to address a broad range of immune diseases, including atopic dermatitis. Clinical data in atopic dermatitis now confirms that soquilitinib appears to be safe oral medicine that produces deep responses that are durable with relatively short treatment periods, including in patients who have received prior systemic therapies. It blocks multiple critical immune cell signaling pathways that reduce inflammatory cytokines and rebalance cellular immune function through effects on Tregs and other cells. Looking forward, we have multiple value creation opportunities for socolitinib. Phase II clinical trials in AD, hydradenitis superotiva, and asthma are planned to start in 2026. A phase 3 registration trial is ongoing in relapsed peripheral T-cell lymphoma. Finally, we have a strong intellectual property position on socolitinid. The composition of matter patents have issued in major territories providing protection through 2042. Other patent applications covering methods of use, monitoring, et cetera, have been filed. Since we invented Soqualitinib, there are no royalty or other financial obligations related to the IP of this drug. In closing, we are very excited about our IT program, as we believe it will have broad applications across many areas of medicine. On a personal note, I consider SoQuilinib to potentially be a revolutionary approach to the treatment of immune diseases. I am very proud to work alongside our talented and dedicated employees and collaborators as we bring this important new therapy to patients. Thank you. Operator, I think we can now open the call for Q&A.

Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by the one on your touchstone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press star followed by the two. If you are using a speakerphone, please lift the handset before pressing any keys. Your first question comes from Roger Song with Jeffries. Your line is now open.

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

Okay. Thank you for the question, Roger.

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

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

Okay, so first of all, the cohort three data, the baseline was about six and a half to seven, if you look at the curve I showed. In cohort four, it's 7.2.

Okay, Okay. That's the average, I guess, 7.2. Yeah.

So we did not require a baseline itch score, a PPNRS score of a certain level, which we are going to be requiring in our phase two trial. And obviously, if you don't, if you have a low PPNRS, then it's difficult to show the four point change. So, in our future trials, we'll require at least four or more. So, I know others talk about percent change, and that's really not a very good way to look at it. It is a patient reported score. It's highly variable. We did not really rigorously collect it in our phase one because we were more interested in safety and objective efficacy parameters. In our phase two, It'll be done more rigorously with electronic capture or reporting and very uniform requirements for when the patient does it. It's influenced by a lot of things. What time of the day the patient reports the score, where they are, how happy they are, things like that. So it's an important endpoint, but it has to be captured very rigorously. In any event, we see a very nice change in itch in our Cohort 3, and I think you can see from the biomarker data that Cohort 3 and 4 seem to be producing more effects. Okay?

Yeah, thank you, Rich. Last question from us. In your Phase 2 design, you decided to include a 400-milliogram QD as one of those cohorts. Just curious about the risk of reward, given you haven't tested those cohorts, the QD, but you also mentioned the durable PD effect. Do you need that QD to make a FQL to be very commercially viable?

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

So we will have data on that. Got it. Thank you. Congrats again. Thanks.

Your next question comes from Aiden Husanoff with Lautenberg. Your line is now open.

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

I think that socolitinib could be a first-line treatment for atopic dermatitis or later line. I think that our clinical trial and our planned phase 2 clinical trial, where we also enroll experienced prior systemic therapy patients, will position us to be a drug that would be use frontline or later line. You know, of course, as these other agents are out there, more and more patients are becoming treatment experience. So, I think the beauty of our drug is that we have a drug now where we're showing that it doesn't matter whether you use a first line or later line. And so, I think that whole, that entire indication is open for us. Now, do I think dermatologists would prefer to use our frontline, our agent frontline. Well, I think it's safe. It's convenient. I also think that we don't have the rebound phenomenon that all these other treatments have. I mean, that's pretty clear already. So I think that there's no reason not to use our drug frontline.

Got it. Yeah, it makes sense.

I'm trying to understand the easy the curves for socolutinib and when they make potential plateaus. I'm looking at re-invoke easy curves. I think they plateaued week eight, and the Pyxin curves plateaued well. So for socolutinib, so it still seems to be pretty steep at week eight. So given the mechanism of action, the ITK inhibition, when do you think theoretically the curve can plateau? What would week 12, 16, 24? I'm just curious to hear your thoughts on this.

Well, you can't go below 100, so it's going to plateau somewhere. But it does look like there's a straight downward slope continuing, as you point out. And that's one of the reasons we're going in 12 weeks in our phase two. I mean, it's going to plateau out somewhat. I mean, I'd be careful, you know, cross-trial comparisons are always dangerous and especially dangerous in AD and especially now where you have a lot of other treatments out there now. So, you know, trying to compare us to a Dupixin curve from years ago in a naive population is difficult. I think you can see from our demographics that, you know, we have 35% of our patients had a prior therapy. you can see, and that makes a difference in the disease as shown by our placebos. Now, we also only have 24 subjects in cohort four. It's a good trial, one-to-one randomization, well-balanced, but it's only 24 subjects. So, I don't know where it's going to plateau, but we're going to test it beyond the eight weeks. Now, I do think that we're moving into a paradigm shift in how we may treat this disease. If we're talking about resetting immunity, then, and not just blocking a factor, not just blocking a cytokine, but resetting the immune system, then we're in an era now where you can talk maybe about intermittent therapy, where you would treat for some period of time and just watch patients and disease comes back retreat them. And, you know, I've been through that before. That's, that's the rituxan story in lymphoma, where intermittent therapy became a way to manage low-grade lymphoma for years, for years. And, you know, I personally have had patients I took care of with rituxan where they had intermittent therapy over 20 years. That's how old I am. And I think that's a good strategy. I think the current therapies for AD, where you take a drug for months and months and you stop and the disease comes back in a few months, that's not very satisfying. Patients don't like diseases to come back that soon. They don't like the diseases at all. And they don't like to take drugs forever either, whether they're oral or injectable. So I think that, I think with our mechanism of action, which is coming into focus now, I think we have an opportunity to establish new paradigms in therapy.

Yeah, makes sense.

And given the lasting T-Rex, and actually it tooks up being used across all three lines of therapies. So I have another question for hydrodinitis superativa. So given the efficacy that you've shown atopic dermatitis, atopic dermatitis is obviously an established market, more than $10 billion. Hidroadenitis suprativa is not established yet, but it could be potentially larger. But curious to hear your thoughts on how suculitinib may position itself in Hidroadenitis suprativa. And actually, across all these three large-term indications, atopic dermatitis, Hidroadenitis suprativa, and psoriasis, what do you think suculitinib may show the largest differentiation versus standard of care, especially IL-17?

Okay. So first of all, the reason we're going out, one of the reasons we're going after HS or hydradenitis superotiva is because it's primarily a TH17 disease. Atopic dermatitis, primarily TH2, although TH2, TH17 are involved in all of them. So there's a strong scientific rationale to go after HS. And, you know, that's the reason we have an oral drug. I forget the name of the drug from UCB, the antibody that requires injections. So again, I think that if we show similar efficacy in HS, you have the same argument. Why not use it frontline? I mean, it seems to be safe and it seems to, if it turns out to be effective in that disease, in our phase one study or in that illness. I don't see why it wouldn't become a front line. And by the way, psoriasis, psoriasis makes a lot of sense for us. We just didn't go into that because it's such a competitive space. You know, now as we get more experience, perhaps we will go into that space. Psoriasis from a scientific rationale was a beautiful disease for us. Th17, other inflammatory components, makes a lot of sense for us. And mechanistically, the story behind our ITK inhibitors getting really interesting and really exciting. And I think we're going to have a good story about that at the SID meeting. I mean, some very interesting things are happening to gene expression for these inflammatory cytokines in the JAK-STAT system. Remember, IL-17 signals through STAT-3, IL-5, STAT-135. So, you know, we affect several of those, which gives us the opportunity to be much broader in terms of our potential indications. Okay.

Thank you.

Very helpful, and congrats again with this great data.

Your next question comes from Lee Wastek with Cantor. Your line is now open.

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

Okay. Thank you for that question. Regarding safety, we have a lot of experience with safety now. And you pointed out, thank you for reminding me about the lymphoma study. We have hundreds of patients now treated with so-called out over months and years. And in the lymphoma study, these are very fragile, usually elderly patients with multi-system problems, tumor infiltration in many organs, liver, kidney, etc., lung, we have not seen a single patient, not a single patient in our lymphoma study has discontinued therapy due to a safety or a toxicity reason. We have not seen any liver function test abnormalities. We've not seen any hematologic suppression. Now, I know some of our tables at meetings show hematologic abnormalities, but in our lymphoma patients, many of our patients come on. They're already anemic. They're already neutropenic, et cetera. So those are not drug related. And so far in our 72, 48 patients with atopic dermatitis, we really don't see any safety signals. In fact, I think our AE rate is lower than placebo, which is, well, you know, which is amazing. So we, you know, we also are not surprised by the safety. We really saw no dose limiting toxicities in animals. We saw no dose many toxicities in our phase one lymphoma study where we went up to 600 milligrams BID. There was no signs of any toxicity, even though we were super saturating the target. So we have no animal tox issues that we've seen. We didn't see it in patients. And again, I said it early in my presentation, there are two reasons for this. Very, very specific drug. Very specific drug. and a target that is very limited. I mean, go look at the human protein atlas of ITK. You'll only find it in some lymphoid tissues. That's where your T cells and NK cells are. Go look at some of these other targets that people look at. They're all over the place. So, you know, my experience with rituxan, one of the reasons rituxan was so good and so safe is that same thing. If you look at where CD20 is expressed, very limited, only in lymphoid tissues where there's B cells. So specificity and selectivity usually go towards safety because you don't have the off-target problems.

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

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

So we're certainly open to that. Okay, great.

Your next question comes from Greg Tvanovich with Mizuho. Your line is now open.

Good morning, Richard. Congrats on the data, and thanks for taking my questions. I've got two to start with. One, can we just revisit the data and the remarkable efficacy results, but in the context of what seems to be a very clean placebo response where you're not seeing anything from easy scores, can you just remind us kind of how you think about what you saw from the placebo group, what might explain very low, easy scores there? And then also, as we go and look forward to the initiation of your phase two study and it being a longer study, what might you think about that placebo-adjusted efficacy? So that's kind of my first question. And my second question, just if you could just remind us of the competitive landscape in terms of the ITK inhibitor players and how your molecule might differentiate from others that may be in development. Thanks.

Okay. So, all right, let's talk about placebos. First of all, we have a placebo. That's the first point. And placebos are very important in these kinds of trials because, as I mentioned, there is some degree of subjectivity and there's a strong psychological component. I don't understand it, but patients, once they start taking these pills, even placebos, they feel better and they even respond, seem to respond to them. So, placebos are very important. Now, in our cohorts one to three, and I know some people have brought this up to me, we had zero placebos reach EZ75. And, you know, look, first of all, it was relatively small sample size. It was only, what, 24 patients or something, placebo. So it's a small sample size, number one. Number two, it was only 28 days of therapy. So you have a short window and the chance of a placebo dipping into the EZ75 is reduced. And thirdly, and I think this is more significant, I'm absolutely convinced that the patient population in cohorts one, two, and three and four, or corvus, are sicker, much sicker than what's been reported in prior literature, especially if you start going back and looking at papers 10 years ago where there was no other therapy these guys were getting. So I think that the cohorts one to three zero was a reflection sicker patient population, short therapeutic window, and small numbers. If we did more patients, we probably would have seen some placebos. Now, in cohort four, we did increase the number of placebos. We had two patients who achieved EZ75. And, you know, that would be 20% or 17%, depending on how you want to count it. That's within the, you know, the range of most studies. So, I don't think there's anything abnormal there. Now, again, I did mention that of those two placebos, they did not receive prior therapy. Of seven placebos that did receive prior therapy, zero achieved EZ-75, zero. You start to see the difference there and how that matters. And whereas we did see EZ-75s, in fact, EZ-90s in some of our active patients. So, you know, We have a 75% reach the EZ75 versus call it 20%. That's a good result. It confirms our cohorts one to three. It puts us in, I think, the efficacy realm of JAK inhibitors, although we don't have, obviously, the treatment experience. But it looks like we have JAK-like activity, better safety, and no rebound, which is, I think, a big point. So our placebos overall, if you look at our, put it all together, our placebo rate is very similar to what other studies are. Maybe it's a little lower, but I would explain that based on sicker patients. Okay, now the second question was ITK landscape. So first of all, we've been pioneers in this space. We have, I should say, we've benefited from lots of great immunologists who did work 20 years ago and over the last several years on this, so we benefit from their great work. But in terms of the clinic and human biology, we've been the pioneers, and the inventive step for us was to be absolutely rigid in our requirement for specificity for ITK. And, you know, a lot of other people, once ibrutinib was successful, everybody started making kinase inhibitors to that family of targets, but they didn't really spend or think much about specificity. But we actually knew from the studies that were published 20 years ago that, gene knockout studies, that specificity was important. And it turns out to be true. I think now we've confirmed that. So I don't know of any specific ITK inhibitor in clinical trials at the moment. But I think after today's call, you can count on a lot of people working on ITK inhibitors. Now they know it needs to be specific. And every one of them, let's see, what, three months from now, I'll say they're better than we are.

So we can count on that.

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

You did. Thanks, Richard.

Your next question comes from Etzer Derute with Barclays. Your line is now open.

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

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

Thank you. Congrats again.

Your next question comes from Jeff Jones with Oppenheimer. Your line is now open.

Good morning, guys, and thanks for taking the question. And just to re-echo, congrats on the really strong data set. I guess one question around the placebo patients in the mean-easy reduction. At the end of therapy, it looked like clearly the sequelaunin patients didn't sort of have a rebound effect. But it was interesting that it looked like the placebo patients seemed to hold on there as well to their response. Any thoughts on what you're seeing there?

Small sample size and also a couple of the placebos flared, and so you can't follow them.

Got it.

Yeah. So that, I think, is the explanation for that. Okay. All right. Oh, and one other thing, Jeff. One other thing. When you have a small reduction in EASY, it becomes easier or harder to, I guess, what am I looking for? it's harder to show a change. I mean, if you're going to rebound and I mean, if you're only if you're only reduced a small amount and you go up a little bit, it's not that, you know, it's not that significant. It's easier to see changes. It's easier to see rebound when you have a big effect, in other words. So if you look at that graph I showed of abracitinib, when you look at the lower doses and placebo, they hardly have any rebound because they didn't respond very well to begin with.

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

Uh, let me turn that over to Lee, uh, to, to Lace.

Yeah, Jeff, that, I mean, those studies are included, um, but I should say, you know, we know we need to raise more capital, and that's pretty clear, and we'll raise more capital when appropriate.

Okay, thank you very much, guys, really appreciate it.

All right, um, okay, Okay. Sorry. We have another question. Let's take one more question, operator.

Okay. Your next question comes from Sean Lee with H.C. Wainwright. Your line is now open.

Okay. Good morning, guys, and congrats on the great data. I just have two quick questions. First, for the upcoming Phase II study, are there any significant differences in the inclusion and exclusion criteria for the patients compared to the phase one?

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

Great. Thank you for that clarity. And my second question is, could you provide a quick highlight of the clinical milestones expected this year and their timings?

So, we expect an interim analysis from our lymphoma study later this year. That's a futility analysis. We expect to start asthma. we expect to start HS. They won't read out until next year, 27. The Phase 2 AD study will take 18 months, approximately, to read out.

Am I forgetting anything? Those would be our milestones.

Great. Thank you very much for that. And that's all I have.

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

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