Temtokibart Shows Benefit, Effect on Biomarkers in Phase 2b Atopic Dermatitis Trial

A pair of presentations on phase 2b data from the European Association of Dermatology and Venereology (EADV) 2025 Congress offer new insight into the effects of temtokibart in adults with moderate-to-severe atopic dermatitis.

Presented as late-breaking data on September 17, 2025, results suggest temtokibart, an investigational monoclonal antibody that targets the IL-22RA1 receptor subunit from Leo Pharma, was associated with significant improvements in several measures of disease severity and activity, with additional analysis shedding light on impact of atopic dermatitis biomarkers.1,2,3

“These results are promising, as they provide further evidence of the value of targeting the IL-22 pathway in AD, via IL-22RA1 , offering a potential novel approach to the currently existing therapies used to treat atopic dermatitis” said Stephan Weidinger, MD, PhD, professor and chair for Dermatology at the Christian-Albrechts-University, director of the Department of Dermatology and Allergy at the University Hospital Schleswig-Holstein, and the International Coordinating Investigator for the Phase 2b trial.1

A randomized, double-blind, placebo-controlled, multi-site, parallel-group, dose-finding trial, the phase 2b study was designed to assess the efficacy and safety of 4 different doses of subcutaneously administered temtokibart in adult patients with moderate-to-severe atopic dermatitis. The primary endpoint is percent change in EASI from baseline to week 16 and the key secondary endpoint was number of treatment-emergent adverse events at week 16.1,2

Weidinger’s presentation at EADV 2025 Congress included 262 adult patients.

Results indicated use of temtokibart was associated with significant improvement in the primary endpoint of percentage change in EASI from baseline for 600 mg (−61.2%, P <.01), 450 mg (−57.1%, P <.05), and 300 mg (−64.3%, P <.01) treatment arms compared with placebo (−41.7%) at week 16. Additional analysis indicated significant improvements were observed in percentage change in EASI as early as week 1 with 450 mg (−22.3%; P <.01) and 300 mg arms (−19.6%; P <.05), and as early as week 2 with 600 mg (−35.0%; P <.05) compared with placebo, which saw improvements in EASI of −8.0% at week 1 and −22.7% at week 2.1,2

Investigators also pointed out these improvements were maintained up to week 32 in the 600 mg (−59.1%; P <.05) and 300 mg (−60.6%; P <.05) arms, despite no treatment use following week 14.1,2

“Patients with moderate-to-severe atopic dermatitis still face numerous unmet needs, so we welcome any new options that could improve their disease while limiting burdensome side effects,” Weidinger added.1

Following the presentation by Weidinger, a subsequent presentation highlighted data from a biomarker analysis of the phase 2b study. This study included data from 22 patients randomized to temtokibart at baseline and 14 temtokibart-treated with data out to 16 weeks.1,3

Results of this analysis suggested a 97% improvement in immune gene expression by week 16 and expression of epidermal barrier-related genes were significantly restored by week 16. Guttman-Yassky pointed out Correlation analysis revealed reductions in EASI and SCORAD were significantly associated with reductions in Th2 and Th17/22 markers (P ≤ .05). Additionally, the analysis suggested DLQI and POEM correlated with reductions of key T-cell, Th2, Th17/Th22 markers (P ≤.05).1,3

“Atopic dermatitis is a complex and heterogenous disease, and there remains a significant need for further understanding the effect of targeting different pathways. By investigating biomarkers in the clinical programs we are increasing our understanding of the disease, moving us closer to a more tailored approach of treating AD via different mechanisms of action,” said Emma Guttman-Yassky, MD, PhD, the Waldman Professor of Dermatology and Immunology and the Health System Chair of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai.1 “These results provide further evidence that the IL-22 pathway is a key driver of disease activity in AD and that there is a strong correlation between clinical effects and dampening of several immune pathways of importance in AD, when targeting the IL-22RA1 subunit.”

References:

1. Leo Pharma. LEO Pharma presents two late-breaking abstracts for temtokibart reporting positive Phase 2b efficacy, safety and biomarker results in moderate-to-severe atopic dermatitis at the 2025 EADV Annual Meeting in Paris. Leo-pharma.com. Published September 17, 2025. Accessed September 18, 2025. https://www.leo-pharma.com/media-center/news/2025-temtokibart-late-breaker-press-release

2. Weidinger S. IL-22RA1 antagonism with temtokibart provides significant early and sustained improvements in atopic dermatitis: results from a phase 2b dose-finding trial. Presented at the European Association of Dermatology and Venereology (EADV) 2025 Congress. Paris, France. September 17-20, 2025.

3. Del Duca, E. Temtokibart, an IL-22RA1 Monoclonal Antibody broadly dampens gene expression markers of activated immune pathways in Atopic Dermatitis: Results from a Phase 2b Trial Subgroup Analysis. Presented at the European Association of Dermatology and Venereology (EADV) 2025 Congress. Paris, France. September 17-20, 2025.