LEO Pharma Presents Late-Breaking Results from the Phase 2a Mechanism of Action Trial of Temtokibart and Dupilumab in Moderate-to-Severe Atopic Dermatitis at the 2024 EADV Annual Meeting

LEO Pharma A/S, a global leader in medical dermatology, today announced positive results from the Phase 2a Mechanism of Action (MoA) trial, which assessed the mechanistic impact of investigational temtokibart and dupilumab in patients with moderate-to-severe atopic dermatitis (AD). Results were shared as a Late Breaker oral presentation at the 2024 EADV Annual Meeting.¹ 

The Phase 2a MoA trial assessed the impact of inhibiting the IL-22RA1 or interleukin 4 receptor alpha (IL-4Rα) on a mechanistic level in patients with moderate-to-severe AD.¹ The results showed that temtokibart 450 mg once every 2 weeks dosing (Q2W, n=8) significantly improved skin hydration faster and to a greater extent than dupilumab 300 mg Q2W (n=4).¹ Temtokibart significantly improved natural moisturizing factors PCA and UCA by Week 1 from baseline (p<0.0001).¹ Subsequent improvement in barrier function markers including terminal differentiation markers and cell adhesion molecules were also shown with temtokibart treatment.¹ In line with its respective MoA, dupilumab showed a strong and consistent decrease in Type 2-associated inflammatory markers particularly in immune cells and fibroblasts.¹ Clinical improvements in EASI and itch NRS from baseline to Week 16 were comparable for temtokibart and dupilumab.¹ These data suggest that IL-22RA1 blockade does not directly affect skin immune cells but can rapidly help improve barrier abnormalities, identifying a potential new MoA for patients with moderate-to-severe AD.¹ 

“The results of this trial provide new insights into the pathophysiology of AD and give us a unique understanding of the mode of action of temtokibart”, said Dr Christine Bangert, MD, Head of the Allergology Task Force of the Austrian Society of Dermatology and Venereology, Head of the atopic eczema outpatient clinic of the Medical University of Vienna, and the Principal Investigator for the Phase 2a MoA trial. “These data suggest that the IL-22 pathway is central to atopic dermatitis pathogenesis, demonstrating that Type 2 inflammation is not the only relevant driver of the disease.”  

Temtokibart is an investigational monoclonal antibody, currently in Phase 2 development for the treatment of moderate-to-severe AD, which blocks the IL-22RA1 receptor subunit thereby inhibiting the effect of the interleukin-22 (IL-22) cytokine, and also partially inhibits IL-20 and IL-24 signaling.^2,3 A Phase 2b dose finding trial is currently ongoing to evaluate the efficacy and safety of different doses of temtokibart in adult patients with moderate-to-severe AD.⁴ The Phase 2b trial has finalized recruitment, and results are expected in Q1 2025. LEO Pharma is also exploring indications outside dermatology for temtokibart in diseases where the IL-22 pathway is known to play a key role. 

“We are encouraged by the results of this AD trial exploring how targeting the disease from different angles with different mechanisms of action impacts disease markers.” said Kreesten Meldgaard Madsen, Chief Development Officer, LEO Pharma. “These results further clarify the mode of action of temtokibart, giving reasons to believe temtokibart could also address unmet needs in other diseases where the IL-22 pathway is known to play a key role. LEO Pharma is currently exploring temtokibart for inflammation induced anemia.” 

LEO Pharma and argenx, a global immunology company, formed a strategic alliance in 2015 to develop innovative antibody-based solutions for the treatment of chronic inflammation that underlies many skin conditions. LEO Pharma and argenx jointly developed temtokibart under an exclusive option and research agreement. LEO Pharma obtained the license to temtokibart in 2022 and now assumes the responsibility to develop and commercialize temtokibart