Cohort analyses from the WILLOW study reveal clear proof of concept in patients with CLE and SLE with active lupus rash, showing clinically meaningful improvement in disease activity at Week 16

WILLOW研究的队列分析揭示了在患有CLE和SLE且有活动性狼疮皮疹的患者中明确的概念验证，显示在第16周疾病活动有临床意义上的改善。

Enpatoran is a potential first-in-class oral therapy for CLE and SLE that is thought to selectively block the activation of Toll-like receptors (TLR)7 and TLR8

恩帕托兰是一种潜在的首创口服治疗CLE和SLE的药物，被认为可以选择性阻断Toll样受体（TLR）7和TLR8的激活。

Lupus rash can lead to physical discomfort and emotional distress, highlighting the need for effective treatments to manage its signs and symptoms

狼疮皮疹可能导致身体不适和情绪困扰，突显了有效治疗以管理其症状的必要性。

Merck, a leading science and technology company, today announced positive data on enpatoran, an investigational, oral, novel TLR7/8 inhibitor, demonstrating clinically meaningful reduction in disease activity in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) with active lupus rash.

默克公司，一家领先的科技公司，今天宣布了关于enpatoran的积极数据。Enpatoran是一种研究中的口服新型TLR7/8抑制剂，数据显示其在皮肤红斑狼疮（CLE）和伴有活动性狼疮皮疹的系统性红斑狼疮（SLE）患者中显著降低了疾病活动度。

The findings are from Cohort A of the Phase 2 WILLOW study .

这些发现来自第 2 阶段 WILLOW 研究的 A 组队列。

(NCT05162586

(NCT05162586)

). Results will be presented at the 16th International Congress on Systemic Lupus Erythematosus (LUPUS 2025), taking place May 21-24 in Toronto.

）。结果将在第16届国际系统性红斑狼疮大会（LUPUS 2025）上公布，会议将于5月21日至24日在多伦多举行。

WILLOW is a global, multicenter, randomized, placebo-controlled Phase 2 study evaluating three doses of enpatoran taken twice daily (25 mg, 50 mg and 100 mg) versus placebo plus standard of care (SoC) over 24 weeks. The study features a unique design across two lupus cohorts, including both patients with active SLE and CLE.

WILLOW 是一项全球性、多中心、随机、安慰剂对照的 2 期研究，评估每日两次服用三种剂量的 enpatoran（25 毫克、50 毫克和 100 毫克）与安慰剂加标准治疗（SoC）相比，持续 24 周的效果。该研究在两个狼疮队列中采用了独特设计，包括活动性 SLE 和 CLE 患者。

Cohort A focused on patients with CLE or SLE with active lupus rash and evaluated organ-specific disease activity using the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score, a well-defined endpoint in CLE studies that measures different aspects of mucocutaneous manifestations.

队列A重点关注患有CLE或SLE且有活动性狼疮皮疹的患者，并使用皮肤红斑狼疮疾病面积和严重指数活动（CLASI-A）评分评估器官特异性疾病活动，该评分是CLE研究中定义明确的终点，用于衡量黏膜皮肤表现的不同方面。

Cohort B was designed to evaluate the effect of enpatoran on systemic disease activity of SLE patients with the BICLA response endpoint..

B组旨在评估enpatoran对系统性红斑狼疮患者全身疾病活动的影响，以BICLA反应终点为指标。

Cohort A met its primary endpoint, demonstrating a dose-response relationship and showing a clinically meaningful improvement in CLASI-A scores at Week 16 (p = 0.0002). Additionally, at Week 24 up to 91.3% of patients receiving enpatoran achieved a CLASI-50 response (≥50% improvement from baseline), and up to 60.9% achieved a CLASI-70 response (≥70% improvement), compared with 38.5% and 11.5%, respectively, in the placebo group.

A组达到了主要终点，显示出剂量反应关系，并在第16周时CLASI-A评分有临床意义上的改善（p = 0.0002）。此外，在第24周，接受enpatoran治疗的患者中多达91.3%达到了CLASI-50应答（较基线改善≥50%），多达60.9%达到了CLASI-70应答（较基线改善≥70%），而安慰剂组在这两项上的比例分别为38.5%和11.5%。

In this cohort, enpatoran was well-tolerated, and exhibited a manageable safety profile consistent with previous studies, with no new safety signals identified..

在此队列中，enpatoran 耐受性良好，表现出与先前研究一致的可控安全性，未发现新的安全信号。

“Lupus can make navigating everyday life difficult. The skin manifestation, known as lupus rash, often comes with persistent itching, which can lead to scarring and hair loss. This can significantly impact the physical, emotional and social well-being of those living with lupus, underscoring the urgent need for effective treatments,' said Jan Klatt, Head of Development Unit Neurology & Immunology for the Healthcare business of Merck.

“狼疮可导致日常生活的困难。被称为狼疮疹的皮肤表现常伴有持续瘙痒，可能导致疤痕和脱发。这会严重影响狼疮患者的身体、情感和社会福祉，突显了对有效治疗方案的迫切需求，”默克医疗保健业务神经学与免疫学开发部门负责人扬·克拉特表示。

“We are encouraged by the WILLOW results, where we observed clinically meaningful efficacy with a favorable safety profile in people living with lupus rash. Based on these results, discussions with health authorities on a global Phase 3 program with enpatoran are underway.”.

“WILLOW 研究结果令我们备受鼓舞，我们发现恩帕托兰在治疗狼疮性皮疹患者中展现出具有临床意义的疗效和良好的安全性。基于这些结果，我们正在就恩帕托兰的全球 III 期项目与卫生当局进行讨论。”

In addition, and confirming the biological activity, treatment with enpatoran in Cohort A also led to a rapid reduction in interferon gene signature scores beginning at Week 2, which was maintained to Week 24, confirming the involvement of the TLR7/8 pathway in interferon activation in CLE. Overall, evidence from the WILLOW study supports the continued development of enpatoran as a treatment for autoimmune diseases like lupus..

此外，证实了生物活性后，A组患者使用恩帕托兰治疗还导致干扰素基因特征评分从第2周开始迅速下降，并且在第24周时仍然保持降低，这证实了TLR7/8通路与CLE中干扰素激活的相关性。总体而言，WILLOW研究的证据支持继续开发恩帕托兰作为治疗狼疮等自身免疫性疾病的药物。

On Cohort B of the WILLOW study, promising efficacy results were observed in prespecified subpopulations, even though the primary endpoint of dose response was not met. The full readout from this cohort will be presented at the European Alliance of Associations for Rheumatology Congress (EULAR 2025)..

在WILLOW研究的B组中，尽管剂量反应的主要终点未达到，但在预先设定的亚组人群中观察到了令人鼓舞的疗效结果。该组的完整数据将在2025年欧洲风湿病学协会联盟大会（EULAR 2025）上公布。

Principal investigator Prof. Eric Morand of Monash University and Monash Health, said, “These new findings offer promising evidence that, with enpatoran, we may be able to advance outcomes, which remain suboptimal for most patients. The data from the WILLOW study further our understanding of TLR7/8 inhibition in SLE and CLE, which is a novel mechanism of action that may offer new hope for patients.”.

莫纳什大学和莫纳什健康中心的首席研究员埃里克·莫兰教授表示：“这些新发现提供了令人鼓舞的证据，表明通过恩帕托兰，我们或许能够改善目前对大多数患者而言仍不理想的治疗结果。WILLOW 研究的数据加深了我们对 TLR7/8 抑制在系统性红斑狼疮（SLE）和皮肤红斑狼疮（CLE）中的理解，这是一种新颖的作用机制，可能为患者带来新的希望。”

Toll-like receptors (TLR)7 and TLR8 play a relevant role in lupus pathogenesis and are associated with severe manifestations of the disease. By inhibiting these key disease drivers, enpatoran’s unique proposed mechanism of action aims to enhance therapeutic efficacy while preserving the body's immune response, potentially overcoming limitations of existing lupus therapies..

Toll样受体（TLR）7和TLR8在狼疮发病机制中发挥重要作用，并与疾病的严重表现相关。通过抑制这些关键的疾病驱动因子，enpatoran独特的提出的作用机制旨在提高治疗效果，同时保留身体的免疫反应，可能克服现有狼疮疗法的局限性。