AD Pipeline Watch: Corvus Pharmaceuticals’ ITK Inhibitor Shows Promise in Phase 1 AD Trial

Corvus Pharmaceuticals, Inc.’s Soquelitinib demonstrated a favorable safety profile and efficacy profile in patients with moderate to severe atopic dermatitis (AD), according to interim data from a Phase 1 clinical trial.

Soquelitinib (formerly CPI-818) is an investigational small molecule drug given orally designed to selectively inhibit interleukin (IL)-2-inducible T cell kinase (ITK), an enzyme that is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function.

“We are pleased with the early results of our soquelitinib Phase 1 AD clinical trial, which show an attractive potential product profile at the lowest dose we are studying,” says Richard A. Miller, MD, Co-founder, President and Chief Executive Officer of Corvus. “The data show consistent signs of efficacy, combined with a novel mechanism of action, a convenient oral route of administration and a favorable safety profile. This is also supported by an analysis of serum cytokine levels, which show a possible relationship between clinical response and reductions in IL-5, IL-17, IL-31, IL-33 and thymic stromal lymphopoietin (TSLP), along with a trend for serum thymus and activation-regulated chemokine (TARC). We believe the data highlights soquelitinib’s potential as a new treatment option for AD and the broader opportunity for ITK inhibition for other immune related diseases. In addition to blocking the production of multiple inflammatory cytokines, soquelitinib may have persistent direct effects on immune cell function that act to regulate aberrant immune responses. We look forward to completing the Phase 1 trial and initiating other trials with soquelitinib for immune diseases.”

The randomized, double-blind, placebo-controlled Phase 1 clinical trial is slated to enroll 64 patients with moderate to severe AD that previously failed one prior topical or systemic therapy. Patients are enrolled into one of four dosing cohorts in a 3:1 ratio (12 active and 4 placebo) to receive either soquelitinib or placebo. The cohorts are sequentially enrolled and will examine 100mg oral twice per day, 200mg oral once per day, 200mg oral twice per day and 400mg oral once per day. Patients are treated for 28 days and are then followed for an additional 30 days with no therapy.

These doses were selected based on the Company’s prior experience evaluating soquelitinib in T cell lymphoma patients. The doses in the AD trial bracket the 200 mg oral twice a day dosing regimen, which is the level that has been shown to provide complete ITK occupancy and that is being evaluated in the Company’s ongoing registrational Phase 3 clinical trial of soquelitinib in peripheral T cell lymphoma.

The primary endpoints include safety and tolerability, and efficacy, measured by improvement in Eczema Area and Severity Index (EASI) score, Investigator Global Assessment (IGA), reduction in itch and various cytokine biomarkers. EASI scores are also evaluated by the percent of patients that achieve a specified percent reduction in EASI score – EASI 50 for patients that achieved a 50% reduction; EASI 75 for a 75% reduction; and EASI 90 for a 90% reduction. Corvus and a data monitoring committee will be able to monitor the data from the trial as the trial progresses.

The Company is reporting complete results from Cohort 1 of the trial, which includes 16 patients (12 that received soquelitinib 100mg oral twice per day and four that received placebo) with follow up at 28 days and at 58 days. At 58 days, two patients in the soquelitinib group were not available for follow up. The soquelitinib and placebo patients were well matched; see Table 1 below for patient characteristics.

• The mean baseline EASI and IGA scores for soquelitinib patients were 20.4 and 3.0, respectively, compared to an EASI score of 18.5 and an IGA score of 3.3 for placebo patients.
• All soquelitinib patients discontinued topical corticosteroids prior to enrollment, while one placebo patient continued topical corticosteroid treatment. All patients, except the one placebo, discontinued topical corticosteroids for at least 27 days prior to enrolling in the study.
• Cohort 1 included a high proportion of African American patients: 50% of the soquelitinib group and 100% of the placebo group. African Americans with AD are known to have a less favorable prognosis compared to other patient populations.

Cohort 1 Efficacy Data
The cohort 1 EASI and IGA scores are shown in Table 2 below.

• EASI scores at 28-day and 58-day follow-up demonstrate a favorable effect of soquelitinib treatment compared to placebo.
• The soquelitinib mean EASI score reduction was 55.9% at 28 days (n=12) compared to mean EASI reduction of 27.0% in placebo. At day 58, continued improvement in the soquelitinib group was seen with mean EASI reduction of 69.1% (n=10) compared to mean EASI reduction of 19.1% for the placebo group.
• At day 28, in the soquelitinib group, nine of 12 patients achieved EASI 50; three of 12 achieved EASI 75 and one of 12 achieved EASI 90. Three of 12 patients achieved IGA 0 or 1. In the placebo group, two of four patients achieved EASI 50 and no patients achieved EASI 75, EASI 90 or IGA 0 or 1.
• At day 58, in the soquelitinib group, nine of 10 patients achieved EASI 50, four of 10 achieved EASI 75 and one of 10 achieved EASI 90. Three of 10 patients achieved IGA 0 or 1. In the placebo group, one in four patients achieved EASI 50 and no patients achieved EASI 75, EASI 90 or IGA 0 or 1.
• The timing of EASI improvement in the soquelitinib group indicates that a treatment effect begins early, at eight days, and continues for the remainder of the study. (See Figures 1 and 2 below). All soquelitinib treated patients showed improvement in EASI scores.
• The small number of placebo patients demonstrates a variable course over the treatment period with no substantial change over the 58-day period.

Figure 1: Mean EASI Score Change from Baseline (%) for Soquelitinib Treatment Group (N=12 at day 28 and N=10 at day 58)

Figure 2: Mean EASI Score Change from Baseline (%) for Placebo Group (N=4)

Cohort 1 Safety Data
No significant safety issues were observed. All the patients completed 28 days of dosing. One patient reported Grade 1 nausea that did not interfere with the subject receiving the full treatment course, and one patient developed COVID-19 on day 28 of treatment; that patient had an uneventful recovery. No clinically significant laboratory abnormalities were seen. See Table 3 below.

Serum Cytokine Changes
Relationships between reductions in certain cytokines with improvement in EASI scores were observed. Significant cytokines changes were seen for IL-5, IL-17, IL-31, IL-33, TSLP and a trend for TARC in EASI 50 responders (N=9) compared to non-responders (N=3). No such relationships were seen in the placebo group.

Cohort 2 Initial Efficacy and Safety Data
As of December 16, the Company has enrolled 12 patients in Cohort 2 of the trial (soquelitinib 200 mg oral once per day). As of December 7, Day 28 follow up data is available for three patients with efficacy results consistent with that seen in Cohort 1. No clinically significant laboratory abnormalities or treatment related adverse events have been reported in any of the patients enrolled in Cohort 2.