Temtokibart Shows Efficacy and Strong Biomarker Response in Phase 2b Trial for Atopic Dermatitis

In findings from a phase 2b dose-finding trial of the investigational monoclonal antibody temtokibart, the interleukin- (IL) 22 inhibitor was associated with improved clinical outcomes and reduced disease-associated biomarkers in adults with moderate-to-severe atopic dermatitis (AD).

Stephan Weidinger, MD, PhD

Courtesy of Skin Health Institute

Results from the randomized, double-blind, placebo-controlled study were presented on behalf of Leo Pharma during 2 late-breaking sessions at the European Academy of Dermatology and Venereology (EADV) Annual Meeting in Paris, held September 17-20.

The study included 262 adults with moderate-to-severe AD who were randomly assigned to receive one of 3 doses of temtokibart or placebo. The primary endpoint was defined as percentage change in the Eczema Area and Severity Index (EASI) at week 16 and the key secondary endpoint was treatment-related adverse events (AEs), also at week 16. One late-breaking presentation reported efficacy and safety data with a biomarker analyses presented in a second session.

Temtokibart Efficacy and Safety

Investigators reported significant improvement in the primary endpoint, with mean percentage change in EASI from baseline of: −61.2% for 600 mg (P <.01), −57.1% for 450 mg (P <.05), and −64.3% for 300 mg (P <.01). These changes were compared to a mean percentage change for placebo of −41.7% at the 16-week mark.

Investigators observed improvement as early as week 1 in the the 450 mg (−22.3%; P <.01) and 300 mg (−19.6%;P <.05) groups, and at week 2 in the 600 mg group (−35.0%; P <.05), vs placebo (week 1: −8.0%; week 2: −22.7%).

Although there was no further temtokibart treatment after week 14, EASI index changes were maintained through week 32 in the 600 mg (−59.1%) and 300 mg (−60.6%) groups (both P <.05).

Analyses for the key secondary endpoint showed that temtokibart was well tolerated, with no dose-dependent AEs, low incidence of conjunctivitis, and no herpes signal, according to Leo Pharma. Discontinuation due to adverse events was reported in 2.4% of temtokibart-treated participants and in 3.8% of placebo-treated participants.

“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,” Professor Stephan Weidinger, international coordinating investigator for the trial, said in a statement. “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 is professor and chair for dermatology at the Christian-Albrechts-University and director of the department of dermatology and allergy at the University Hospital Schleswig-Holstein, Germany.

Emma Guttman-Yassky, MD, PhD

Courtesy of Icahn School of Medicine

Positive Biomarker Outcomes

In addition to clinical outcomes, biomarker analyses from the phase 2b trial showed that pooled temtokibart-treated participants (n=22 baseline, n=14 week 16) experienced a near complete (97%) improvement in immune gene expression by week 16. Further, the researchers reported significant restoration of expression of epidermal barrier-related genes. When they conducted correlation analyses, the findings indicated that reductions in EASI and SCORing Atopic Dermatitis scores were significantly associated with decreases in Th2 and Th17/22 markers (P ≤.05), and improvements in patient-reported outcomes (DLQI and POEM) correlated with reductions in key T-cell, Th2, and Th17/22 markers (P ≤.05

“Atopic dermatitis is a complex and heterogenous disease, and there remains a significant need for further understanding the effect of targeting different pathways,” Professor Emma Guttman-Yassky, senior author of the biomarker abstract, said in the Leo Pharma statement. “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.” Guttman-Yassky is Waldman professor of dermatology and immunology and health system chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, in New York, NY.

Complementary Mechanism of Action

Blocking IL-22 signaling adds an important mechanism to the therapeutic choices against AD. IL-22 is implicated in epidermal hyperplasia, barrier dysfunction, and heightened disease severity. Studies have shown that individuals with moderate-to-severe AD and high baseline IL-22 expression treated with another investigational IL-22 blocker achieved much greater reversal of the AD transcriptomic profile than those treated with placebo.² IL-22 inhibition also downregulates multiple immune pathways including Th1, Th2, Th17, and Th22 arms and correlates with decreased clinical signs (eg, EASI, SCORAD) in treated patients. IL-22 inhibition may complement existing IL-4/IL-13 and JAK-targeted therapies, advancing more tailored treatment strategies in atopic dermatitis.³

References

1. 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. News release. Leo Pharma. September 17, 2025. Accessed Sept 18, 2025. https://www.leo-pharma.com/media-center/news/2025-temtokibart-late-breaker-press-release

2. Brunner PM, Pavel AB, Khattri S, et al. Baseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab. J Allergy Clin Immunol. 2019;143(1):142-154. doi: 10.1016/j.jaci.2018.07.028

3. Zhou G, Huang Y, Chu M. Clinical trials of antibody drugs in the treatments of atopic dermatitis. Front Med. 2023;10. doi:10.3389/fmed.2023.1229539