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

• Results presented at the Late Breaker Session on September 26^th at the European Dermatology Congress, European Academy of Dermatology & Venereology (EADV) 2024, showed that the investigational interleukin 22 receptor, alpha 1 (IL-22RA1) inhibitor temtokibart induced fast (Week 1) molecular responses¹
• Markers of skin hydration (natural moisturizing factors) 2-pyrrolidone-5-carboxylic acid (PCA) and urocanic acid (UCA) were significantly improved from baseline at Week 1 in the temtokibart group (p<0.0001)¹
• Both temtokibart and dupilumab led to comparable changes in eczema area and severity index (EASI) and itch numerical rating scale (NRS) at Week 16¹

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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.

About the Phase 2a MoA trial

The temtokibart Phase 2a MoA trial (NCT05470114) was a randomized, double-blind, active comparator-controlled, 16-week, single-site, exploratory, mechanistic trial to assess the effect of temtokibart on the molecular signature and safety in adults with moderate-to-severe AD.^1,5 Patients were randomized 2:1 to receive either temtokibart 450 mg Q2W (n=8) or dupilumab 300 mg Q2W (n=4), for 16 weeks.¹ The primary endpoint was change in gene expression typically associated with AD in lesional skin biopsies from baseline to Week 4.⁵ The key secondary endpoint was number of treatment-emergent adverse events from baseline to Week 16 per subject.⁵

About the Phase 2b trial

The temtokibart Phase 2b trial (NCT05923099) is an ongoing randomized, double-blind, placebo-controlled, multi-site, parallel-group, dose finding trial to evaluate the efficacy and safety of different doses of subcutaneously administered temtokibart in adult patients with moderate-to-severe AD.⁴ Patients were randomized to receive one of four doses of temtokibart or placebo.⁴ The primary endpoint is percent change in EASI score from baseline to Week 16.⁴ The key secondary endpoint is number of treatment-emergent adverse events from baseline to Week 16 per subject.⁴

About atopic dermatitis

AD is a chronic, inflammatory skin disease characterized by intense itch and eczematous lesions.⁶ AD is the result of skin barrier dysfunction and immune dysregulation, leading to chronic inflammation.⁷ Type 2 cytokines, including IL-13, play an important role in the key aspects of atopic dermatitis pathophysiology.^8,9 Excessive IL-22 production is also known to contribute to the pathogenesis of AD.^10,11

About investigational temtokibart

Temtokibart is an investigational monoclonal antibody that targets the IL-22RA1 receptor subunit, currently in Phase 2 development for the potential treatment of moderate-to-severe AD.^2,3 It blocks the IL-22RA1 subunit and thereby inhibits the effects of the IL-22 cytokine, and also the effects of IL-20 and IL-24 signaling.^2,3 Temtokibart does not bind to the IL-22 cytokine itself.^2,3 LEO Pharma has obtained a worldwide exclusive license to develop and commercialize temtokibart from argenx.

About LEO Pharma

LEO Pharma is a global company dedicated to advancing the standard of care for the benefit of people with skin conditions, their families and society. Founded in 1908 and majority owned by the LEO Foundation, LEO Pharma has devoted decades of research and development to advance the science of dermatology, and today, the company offers a wide range of therapies for all disease severities. LEO Pharma is headquartered in Denmark with a global team of 4,200 people, serving millions of patients across the world. In 2023, the company generated net sales of DKK 11.4 billion. Learn more at www.leo-pharma.com.

References

1. Bangert C, et al. Presented at European Academy of Dermatology & Venereology (EADV) 2024 Annual Meeting, Amsterdam, 25–28 September 2024.
2. Thaçi D, et al. Presented at American Academy of Dermatology (AAD) 2023 Annual Meeting, New Orleans, 17–21 March 2023.
3. Thaçi D, et al. Presented at European Academy of Dermatology and Venereology (EADV) 2023 Annual Meeting, Berlin, 11–13 October 2023.
4. NCT05923099. Available at: clinicaltrials.gov/study/NCT05923099. Accessed September 2024.
5. NCT05470114. Available at: clinicaltrials.gov/study/NCT05470114. Accessed September 2024.
6. Weidinger S, et al. Lancet 2016;387:1109–1122.
7. Boguniewicz M, et al. Immunol Rev 2011;242:233–246.
8. Tubau C, Puig L. Immunotherapy 2021;13:327–344.
9. Bieber T. Allergy 2020;75:54–62.
10. Gittler JK, et al. J Allergy Clin Immunol 2012;130:1344–1354.
11. Nograles K, et al. J Allergy Clin Immunol 2009;123:1244–1252.

MAT-76176 | September 2024

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