LEO Pharma Presents Late-Breaking Results on Temtokibart for Atopic Dermatitis at EADV

At the 2025 European Academy of Dermatology and Venereology (EADV) Congress in Paris, France, LEO Pharma presented 2 late-breaking abstracts highlighting new clinical and biomarker data from a phase 2b trial (NCT05923099) evaluating temtokibart (LEO 138559), an investigational monoclonal antibody targeting IL22RA1, in adults with moderate to severe atopic dermatitis (AD). The findings demonstrated significant and sustained improvements in disease severity, alongside a favorable safety profile and compelling biomarker evidence supporting the mechanism of action.

Methods and Materials

The phase 2b trial was a randomized, double-blind, placebo-controlled, multisite, parallel-group, dose-finding study conducted across multiple sites, involving 262 adult patients with moderate to severe AD. Patients received subcutaneous temtokibart at 1 of 4 dose levels (600 mg, 450 mg, 300 mg, or 150 mg) or placebo, with primary efficacy evaluated at week 16. The primary end point is the percent change in Eczema Area and Severity Index (EASI) from baseline to week 16. The key secondary end point is the number of treatment-emergent adverse events from baseline to week 16 per patient.

Safety and Efficacy

Temtokibart met its primary end point, showing statistically significant reductions in EASI scores at week 16 for the 3 highest doses: 300 mg (–64.3%; P < .01), 450 mg (−57.1%; P < .05), and 600 mg (−61.2%; P < .01).¹ The placebo group showed a mean EASI reduction of −41.7%. Improvements were seen as early as week 1 in the 300-mg and 450-mg groups and week 2 in the 600-mg group. Changes were maintained through week 32 in patients who took the 300-mg and 600-mg doses.

Temtokibart was well tolerated across all doses, with no evidence of dose-dependent adverse events. The incidence of conjunctivitis was low, and there was no observed signal for herpesvirus infections. The rate of adverse effects leading to treatment discontinuation or withdrawal was low and comparable between the temtokibart (2.4%) and placebo (3.8%) cohorts.

“These results are promising, as they provide further evidence of the value of targeting the IL-22 pathway in AD, via IL22RA1, 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 of Kiel, director of the Department of Dermatology and Allergy at the University Hospital Schleswig-Holstein in Germany, and international coordinating investigator for the phase 2b trial. “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 [adverse] effects.”

Biomarker Evidence

In a second late-breaker presentation, Emma Guttman-Yassky, MD, PhD, Waldman Professor of Dermatology and Immunology and the Health System Chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai, shared biomarker data from a subset of patients.² By week 16, a 97% overall improvement in immune gene expression was observed in patients treated with temtokibart. Significant restoration of epidermal barrier–related gene expression was also reported. Clinical outcomes (EASI and SCORing Atopic Dermatitis) correlated strongly with reductions in Th2, Th17, and Th22 cytokine signatures and improvements in quality-of-life metrics (Dermatology Life Quality Index and Patient-Oriented Eczema Measure), also tracked with biomarker changes.

“Atopic dermatitis is a complex and heterogeneous disease, and there remains a significant need for further understanding [of] 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 [to] treating AD via different mechanisms of action,” Guttman-Yassky said. “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 IL22RA1 subunit.”

The investigational monoclonal antibody selectively targets the IL22RA1 receptor subunit, thereby inhibiting the downstream effects of IL-22, IL-20, and IL-24—cytokines known to be upregulated in AD and associated with inflammation, epidermal hyperplasia, and barrier dysfunction. Unlike some other agents, temtokibart does not bind IL-22 directly, which may offer distinct advantages in specificity and safety. LEO Pharma has obtained a worldwide exclusive license to develop and commercialize temtokibart from argenx.

“We are encouraged by these phase 2b results, which further add to the potential clinical value of temtokibart in moderate to severe atopic dermatitis,” said Jacob Pontoppidan Thyssen, PhD, chief scientific officer and executive vice president of science, search, and innovation at LEO Pharma.

References

1. Weidinger S, et al. Presented at: EADV 2025 Congress; September 17-20, 2025; Paris, France.

2. Del Duca E, et al. Presented at: EADV 2025 Congress; September 17-20, 2025; Paris, France.