BALLERUP, Denmark--(BUSINESS WIRE)--NOT FOR UK USE – NOT INTENDED FOR UK MEDIA

丹麦巴勒鲁普——（商业新闻短讯）——不供英国使用——不供英国媒体使用

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.

LEO Pharma A/S是医学皮肤病学的全球领导者，今天宣布了2a期作用机制（MoA）试验的积极结果，该试验评估了研究性temtokibart和dupilumab对中度至重度特应性皮炎（AD）患者的机制影响。结果在2024年EADV年会上作为迟发性口头报告分享。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.

2a期MoA试验评估了抑制IL-22RA1或白细胞介素4受体α（IL-4Rα）对中度至重度AD患者机制水平的影响。结果显示，替莫基巴450 mg，每2周一次给药（Q2W，n=8）比dupilumab 300 mg Q2W（n=4）显着改善皮肤水合作用更快，程度更大。1替莫基巴在第1周时显着改善了天然保湿因子PCA和UCA（p<0.0001）。随后，替莫基巴治疗也显示了屏障功能标志物的改善，包括终末分化标志物和细胞粘附分子。1与各自的治疗一致MoA公司，dupilumab显示2型相关炎症标志物强烈且持续下降，特别是在免疫细胞和成纤维细胞中[1]。从基线到第16周，EASI和瘙痒NRS的临床改善与temtokibart和dupilumab相当[1]。这些数据表明IL-22RA1阻断不直接影响皮肤免疫细胞，但可以迅速帮助改善屏障异常，为中重度AD患者确定潜在的新MoA.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.

“这项试验的结果为AD的病理生理学提供了新的见解，并使我们对temtokibart的作用方式有了独特的理解，”奥地利皮肤病和性病学会变态反应学特别工作组负责人、维也纳医科大学特应性湿疹门诊负责人、2a期MoA试验首席研究员克里斯蒂娜·班格特博士说。

“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.”.

“这些数据表明，IL-22途径是特应性皮炎发病机制的核心，表明2型炎症不是该疾病的唯一相关驱动因素。”。

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.

Temtokibart是一种研究性单克隆抗体，目前处于治疗中重度AD的2期开发阶段，可阻断IL-22RA1受体亚基，从而抑制白细胞介素-22（IL-22）细胞因子的作用，并部分抑制IL-20和IL-24信号传导。2,3目前正在进行2b期剂量发现试验，以评估不同剂量的Temtokibart在中重度AD成年患者中的疗效和安全性。4 2b期试验已完成招募，预计结果将于2025年第1季度公布。

LEO Pharma is also exploring indications outside dermatology for temtokibart in diseases where the IL-22 pathway is known to play a key role..

利奥制药（LEO Pharma）也在探索皮肤病学以外的替莫吉巴特适应症，以治疗已知IL-22途径起关键作用的疾病。。

“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首席开发官Kreesten Meldgaard Madsen说：“我们对这项AD试验的结果感到鼓舞，该试验探索了从不同角度以不同的作用机制靶向疾病如何影响疾病标志物。”。“这些结果进一步阐明了temtokibart的作用方式，有理由相信temtokibart也可以解决已知IL-22途径起关键作用的其他疾病中未满足的需求。

LEO Pharma is currently exploring temtokibart for inflammation induced anemia.”.

LEO Pharma目前正在探索temtokibart治疗炎症性贫血。”。

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和全球免疫学公司argenx于2015年成立了战略联盟，以开发基于抗体的创新解决方案，用于治疗许多皮肤病的慢性炎症。LEO Pharma和argenx根据独家期权和研究协议共同开发了temtokibart。

LEO Pharma obtained the license to temtokibart in 2022 and now assumes the responsibility to develop and commercialize temtokibart..

利奥制药（LEO Pharma）于2022年获得了temtokibart的许可证，现在负责开发和商业化temtokibart。。

About the Phase 2a MoA trial

关于 MoA 2a 阶段试验

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.

temtokibart 2a期MoA试验（NCT05470114）是一项随机，双盲，主动比较对照，16周，单点，探索性，机制试验，旨在评估temtokibart对中度至重度AD患者分子特征和安全性的影响。1,5名患者被随机分为2:1，接受temtokibart 450 mg Q2W（n=8）或dupilumab 300 mg Q2W（n=4），持续16周。1主要终点是从基线到第4周，病变皮肤活检中通常与AD相关的基因表达发生变化。关键的次要终点是从基线到第4周的治疗紧急不良事件数量第16周每个科目。

About the Phase 2b trial

关于2b期试验

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.

temtokibart 2b期临床试验（NCT05923099）是一项正在进行的随机，双盲，安慰剂对照，多部位，平行组，剂量发现试验，用于评估不同剂量皮下注射替莫基巴对成人中度至重度AD患者的疗效和安全性[4]。患者随机接受四剂替莫基巴或安慰剂中的一剂[4]。主要终点是EASI评分从基线到第16周的百分比变化[4]。关键的次要终点是每个受试者从基线到第16周的治疗紧急不良事件数。

About atopic dermatitis

关于特应性皮炎

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.

AD是一种慢性炎症性皮肤病，其特征是强烈的瘙痒和湿疹病变[6]。AD是皮肤屏障功能障碍和免疫失调的结果，导致慢性炎症[7]。包括IL-13在内的2型细胞因子在特应性皮炎病理生理学的关键方面起着重要作用[8,9]。过量的IL-22产生也被认为是导致AD发病的原因[10,11]。

About investigational temtokibart

关于调查性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..

Temtokibart是一种针对IL-22RA1受体亚基的研究性单克隆抗体，目前正在进行中重度AD的潜在治疗的2期开发。2,3它阻断IL-22RA1亚基，从而抑制IL-22细胞因子的作用，以及IL-20和IL-24信号传导的作用。2,3 Temtokibart不与IL-22细胞因子本身结合。2,3 LEO Pharma已获得全球独家许可，可从argenx开发和商业化Temtokibart。。

About LEO Pharma

关于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.

利奥制药（LEO Pharma）是一家全球性公司，致力于提高护理标准，造福皮肤病患者及其家人和社会。LEO Pharma成立于1908年，由LEO基金会拥有多数股权。LEO Pharma致力于数十年的研究和开发，以推动皮肤病学的发展。如今，该公司为所有严重疾病提供了广泛的治疗方法。

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.

利奥制药（LEO Pharma）总部位于丹麦，拥有4200人的全球团队，为全球数百万患者提供服务。2023年，该公司净销售额为114亿丹麦克朗。