LEO Pharma Announces Positive Preliminary Phase 2b Findings for Temtokibart in Atopic Dermatitis

Temtokibart (LEO 138559), an investigational monoclonal antibody targeting the IL-22RA1 receptor subunit, achieved statistically significant improvements in eczema severity at the 3 highest tested doses in a phase 2b clinical trial of adults with moderate-to-severe atopic dermatitis (AD), according to topline results announced by LEO Pharma on May 9.¹

The trial met its primary endpoint, demonstrating significant percentage reductions from baseline in Eczema Area and Severity Index (EASI) scores at week 16 compared with placebo.¹

The phase 2b study (NCT05923099) was a randomized, double-blind, placebo-controlled, dose-finding trial conducted across multiple clinical sites, the number not disclosed in the statement from LEO. Adults with moderate-to-severe AD were randomized to receive 1 of 4 doses of subcutaneously administered temtokibart or placebo. Treatment with the 3 highest doses produced meaningful clinical improvements by week 16, according to the statement.

The company also described a favorable safety profile, with no dose dependency observed. Adverse events were predominantly mild or moderate, non-serious, and not deemed related to temtokibart treatment. There was no clear dose-response relationship in adverse events observed.¹

Eligible participants had a recent history of inadequate response to topical corticosteroids, with or without topical calcineurin inhibitors, or were considered poor candidates for topical therapy due to safety concerns.² Additional inclusion criteria required EASI score of 12 or greater at screening and of 16 or greater at baseline, a validated Investigator Global Assessment for Atopic Dermatitis score of 3 or more at both time points, and at least 10% body surface area involvement. Participants also needed an Atopic Dermatitis Symptom Diary (ADSD) Worst Itch weekly average score of 4 or greater at baseline. Women of childbearing potential were required to use highly effective contraception during the study and for at least 18 weeks after the last dose of investigational product.²

By selectively blocking the IL-22RA1 receptor subunit, temtokibart inhibits downstream signaling of IL-22, IL-20, and IL-24 cytokines. Elevated levels of IL-22 contribute to AD pathogenesis through effects on epidermal barrier disruption, keratinocyte proliferation, and inflammation, according to the statement. Unlike current therapies that primarily target type 2 cytokines such as IL-4 and IL-13, temtokibart addresses a distinct immunological pathway, which may offer a new therapeutic strategy for patients whose disease is driven by dysregulated IL-22 signaling, Leo said.¹

“Atopic dermatitis is a complex immunological condition, and patients living with this debilitating disease still face unmet needs. These results further add to the understanding of the mode of action of temtokibart and its potential abilities to [meet the needs] in diseases where the IL-22 pathway is known to play a key role,” Jacob Pontoppidan Thyssen, PhD, DmSci, LEO Pharma chief scientific officer and EVP, science, search & innovation, said in the statement.

Pending final analysis, LEO Pharma expects to present full data from the phase 2b trial at upcoming scientific meetings.¹

References
1. LEO Pharma announces positive topline phase 2b results for temtokibart in moderate-to-severe atopic dermatitis. News release. LEO Pharma. May 9, 2025. Accessed May 9, 2025. https://www.leo-pharma.com/media-center/news/2025-leo-pharma-announces-topline-positive-phase-2b-results-for-temtokibart
2. A trial to evaluate the efficacy and safety of different doses of LEO 138559 in adults with moderate-to-severe atopic dermatitis. ClinicalTrials.gov identifier: NCT05923099. Updated May 2, 2025. Accessed May 9, 2025. https://clinicaltrials.gov/study/NCT05923099#study-overview