LEO Pharma presented positive Phase 2b results for its investigational monoclonal antibody temtokibart in moderate-to-severe atopic dermatitis at the 2025 European Academy of Dermatology and Venereology (EADV) Annual Meeting. The randomized, double-blind, placebo-controlled trial in 262 adult patients met its primary endpoint, demonstrating significant improvements in disease severity across three of four tested doses.
Primary Efficacy Results
The Phase 2b dose-finding trial demonstrated that temtokibart achieved significant improvement in the primary endpoint of percentage change in Eczema Area and Severity Index (EASI) from baseline at Week 16. The 600 mg dose showed a -61.2% improvement (p<0.01), the 450 mg dose achieved -57.1% improvement (p<0.05), and the 300 mg dose demonstrated -64.3% improvement (p<0.01), all compared to placebo's -41.7% improvement.
Notably, the drug demonstrated rapid onset of action. Significant improvements in EASI were observed as early as Week 1 for the 450 mg (-22.3%; p<0.01) and 300 mg arms (-19.6%; p<0.05), and by Week 2 for the 600 mg dose (-35.0%; p<0.05), compared to placebo (Week 1: -8.0%, Week 2: -22.7%).
Sustained Efficacy
The trial revealed sustained therapeutic effects extending well beyond the treatment period. Despite no treatment administration after Week 14, significant improvements were maintained up to Week 32 in both the 600 mg (-59.1%; p<0.05) and 300 mg (-60.6%; p<0.05) treatment arms.
"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 Professor Stephan Weidinger, Professor and Chair for Dermatology at the Christian-Albrechts-University 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 side effects."
Biomarker Analysis
Complementary biomarker data presented by Professor Emma Guttman-Yassky from the Icahn School of Medicine at Mount Sinai revealed comprehensive immune pathway modulation. Temtokibart-treated patients demonstrated an overall 97% improvement in immune gene expression by Week 16, with significant restoration of epidermal barrier-related genes.
Correlation analysis showed that reductions in EASI and SCORAD were significantly associated with reductions in Th2 and Th17/22 markers (p≤0.05). Quality of life measures including DLQI and POEM correlated with reductions of key T-cell, Th2, and Th17/Th22 markers (p≤0.05).
"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," Professor Guttman-Yassky explained.
Safety Profile
The safety analysis revealed a favorable tolerability profile across all dose levels. Temtokibart was well-tolerated with no dose-dependent adverse events, a low incidence of conjunctivitis, and no signal for herpes infections. Adverse events leading to permanent drug discontinuation or withdrawal were reported in 2.4% of temtokibart-treated patients compared to 3.8% in the placebo group.
Mechanism of Action
Temtokibart represents a novel therapeutic approach targeting the IL-22RA1 receptor subunit. The monoclonal antibody blocks this receptor, thereby inhibiting the effects of IL-22 cytokine, which is known to be elevated in atopic dermatitis pathways, as well as the effects of IL-20 and IL-24 signaling. Unlike other approaches, temtokibart does not bind to the IL-22 cytokine itself.
Development Partnership
LEO Pharma obtained worldwide exclusive licensing rights to develop and commercialize temtokibart from argenx, following their strategic alliance formed in 2015 to develop innovative antibody-based solutions for chronic inflammatory skin conditions.
"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 Professor Jacob Pontoppidan Thyssen, Chief Scientific Officer & Executive Vice President, Science, Search & Innovation at LEO Pharma.
The Phase 2b trial (NCT05923099) evaluated subcutaneously administered temtokibart across four different doses compared to placebo, with the primary endpoint being percent change in EASI from baseline to Week 16. The drug remains investigational and is not approved by any health authority, with safety and efficacy subject to further larger trials.
