TREK-DX, the first randomized, double-blind, placebo-controlled study to be conducted in a dupilumab-experienced atopic dermatitis (AD) patient population, has started enrolling patients in the US under an updated protocol; new European sites are on track to open in the first half of 2024

TREK-DX是在dupilumab经历的特应性皮炎（AD）患者人群中进行的第一项随机，双盲，安慰剂对照研究，已开始根据更新的方案在美国招募患者；新的欧洲网站有望在2024年上半年开业

In a preliminary review of blinded data from 22 patients treated to date, 45% (10/22) of patients saw at least a 90% reduction in their EASI score (EASI-90) and 50% (11/22) of patients achieved a vIGA score of 0 or 1 (clear or almost clear skin) after 16 weeks. Topline unblinded data from the full dataset is expected at the end of 2024.

在对迄今为止接受治疗的22名患者的盲法数据进行的初步审查中，45%（10/22）的患者EASI评分（EASI-90）至少降低了90%，50%（11/22）的患者在16周后达到了vIGA评分0或1（透明或几乎透明的皮肤）。预计2024年底将从完整数据集中获得非盲数据。

Translational data demonstrates differentiated effects of targeting IL-13R versus IL-4R, suggesting eblasakimab has the potential to be effective in AD patients that do not achieve an adequate response to dupilumab, a significant and underserved patient population with few safe and long-term treatment options.

翻译数据显示靶向IL-13R与IL-4R的不同作用，表明eblasakimab有可能对未对dupilumab产生足够反应的AD患者有效，dupilumab是一种重要且服务不足的患者群体，几乎没有安全和长期的治疗选择。

SAN MATEO, Calif. and SINGAPORE, March 11, 2024 (GLOBE NEWSWIRE) -- ASLAN Pharmaceuticals Ltd. (Nasdaq: ASLN), a clinical-stage, immunology focused biopharmaceutical company developing innovative treatments to transform the lives of patients, today announced that it has begun to enroll patients in the US under an updated protocol in the ongoing TREK-DX trial, studying eblasakimab in dupilumab-experienced patients with moderate-to-severe atopic dermatitis (AD)..

加利福尼亚州圣马特奥和新加坡，2024年3月11日（环球通讯社）--ASLAN Pharmaceuticals Ltd.（纳斯达克：ASLN），一家临床阶段，以免疫学为重点的生物制药公司，开发创新治疗方法来改变患者的生活，今天宣布，它已经开始根据正在进行的TREK-DX试验的最新方案在美国招募患者，在患有中度至重度特应性皮炎（AD）的dupilumab患者中研究eblasakimab。。

TREK-DX is the first randomized, double-blind, placebo-controlled trial to be conducted in AD patients who have been previously treated with dupilumab, a market estimated to reach $10 billion by 20291. Based on findings from the TREK-AD study which highlighted the changing AD patient population in the US, the TREK-DX inclusion criteria have been tightened to enroll patients with a baseline Eczema Area and Severity Index (EASI) score of at least 18, instead of 16.

TREK-DX是第一个针对先前接受过dupilumab治疗的AD患者进行的随机，双盲，安慰剂对照试验，预计到20291年市场将达到100亿美元。根据TREK-AD研究的结果，该研究强调了美国AD患者人群的变化，TREK-DX纳入标准已经收紧，以招募基线湿疹面积和严重程度指数（EASI）评分至少为18的患者，而不是16。

In conjunction with this, independent reviewer confirmation of baseline EASI scores has also been implemented. US sites are now enrolling patients according to the updated criteria and additional sites in Europe are on track to open in the first half of 2024..

与此同时，还实施了独立审稿人对基线EASI分数的确认。美国网站目前正在根据更新的标准招募患者，欧洲的其他网站有望在2024年上半年开业。。

TREK-DX will enroll approximately 75 patients who have discontinued dupilumab treatment for any reason, including inadequate control of AD, loss of access or an adverse event, and treat them with either 400mg eblasakimab or placebo once weekly for 16 weeks. At the time of the data cut off for this preliminary review of blinded data from 22 patients enrolled under the original inclusion criteria, who were randomized 2:1 active to placebo, 17 patients completed the 16 week treatment period and 5 patients discontinued before the completion of the 16 week treatment period.

TREK-DX将招募大约75名因任何原因停止dupilumab治疗的患者，包括AD控制不足，无法进入或不良事件，并每周一次用400mg eblasakimab或安慰剂治疗16周。在对根据原始纳入标准入选的22名患者的盲法数据进行初步审查时，他们被随机分为2:1的安慰剂组，17名患者完成了16周的治疗期，5名患者在16周治疗期结束前停药。

At 16 weeks or the last visit, EASI score decreased at least 90% (EASI-90) in 10 patients, or 45%, and 11 patients, or 50%, achieved a validated Investigator Global Assessment (vIGA) score of 0 or 1 (clear or almost clear skin). Of the 9 patients who previously had an inadequate response to dupilumab, 5 patients (56%) achieved EASI-90 and 5 patients (56%) a vIGA score of 0 or 1.

在16周或最后一次就诊时，EASI评分在10名患者中下降了至少90%（EASI-90），即45%，11名患者（即50%）达到了经过验证的研究者全球评估（vIGA）评分0或1（透明或几乎透明的皮肤）。在之前对dupilumab反应不足的9例患者中，5例（56%）达到EASI-90，5例（56%）vIGA评分为0或1。

Treatments have been well-tolerated to date and no new safety signals were identified. There have been no reports of conjunctivitis and no reports of injection site reactions. Topline unblinded data from the full dataset is expected at the end of 2024..

迄今为止，治疗耐受性良好，没有发现新的安全信号。没有结膜炎的报道，也没有注射部位反应的报道。预计2024年底将从完整数据集中获得非盲数据。。

“63% of dupilumab-treated patients fail to achieve clear or almost clear skin (IGA score of 0 or 1) after 16 weeks2, and around half of those patients that do achieve this response do not maintain it after the subsequent 36 weeks3, so there is a significant need for additional biologic therapies that could provide a safe and efficacious long-term treatment option for patients that do not achieve an adequate response to dupilumab.

“63%接受dupilumab治疗的患者无法获得清晰或几乎清晰的皮肤（IGA评分为0或1）在16周后2，大约一半确实达到这种反应的患者在随后的36周后没有维持这种反应3，因此非常需要额外的生物疗法，可以为那些对dupilumab没有达到足够反应的患者提供安全有效的长期治疗选择。

EASI-90 and vIGA are among the most stringent of endpoints in AD studies. Although this is based on a preliminary review of the blinded data, we are encouraged to observe a high percentage of patients in the TREK-DX study meeting these endpoints to date. Our market research found that most AD patients are only moderately satisfied with their current treatment.

EASI-90和vIGA是AD研究中最严格的终点之一。尽管这是基于对盲法数据的初步审查，但我们鼓励在TREK-DX研究中观察到迄今为止达到这些终点的患者比例很高。我们的市场研究发现，大多数AD患者对目前的治疗只有中等程度的满意度。

This, together with the translational data we have generated, supports the potential role of eblasakimab as a treatment for these patients, and the data we are generating in the TREK-DX study could demonstrate that, for many patients, eblasakimab could control their disease even where dupilumab has not,” saidDr Carl Firth, Chief Executive Officer, ASLAN Pharmaceuticals..

这与我们产生的翻译数据一起支持了eblasakimab作为这些患者治疗的潜在作用，我们在TREK-DX研究中产生的数据可以证明，对于许多患者来说，eblasakimab可以控制他们的疾病，即使dupilumab没有，”ASLAN Pharmaceuticals首席执行官saidDr Carl Firth说道。。

Translational data demonstrates differentiated effects of targeting IL-13R versus IL-4R, suggesting eblasakimab has the potential to be effective even in instances where dupilumab is not

翻译数据表明，靶向IL-13R与IL-4R的作用不同，这表明即使在dupilumab不存在的情况下，eblasakimab也有可能有效

Eblasakimab targets the IL-13 receptor (IL-13R) subunit of the Type 2 receptor, preventing signaling through both interleukin 4 (IL-4) and interleukin 13 (IL-13). Both are key drivers of inflammation in AD, however, recently published translational data highlighted the advantages of targeting IL-13R by eblasakimab over the IL-4 receptor (IL-4R), the target of dupilumab, in AD patient peripheral blood mononuclear cells4.

Eblasakimab靶向2型受体的IL-13受体（IL-13R）亚基，阻止通过白细胞介素4（IL-4）和白细胞介素13（IL-13）的信号传导。两者都是AD炎症的关键驱动因素，然而，最近发表的翻译数据强调了在AD患者外周血单核细胞中，依布拉沙单抗靶向IL-13R优于IL-4受体（IL-4R）（dupilumab的靶标）4。

IL-13R blockade resulted in more efficient reduction of cytokines implicated in Type 2-driven (allergic) inflammation compared to IL-4R blockade, as well as lower levels of Type 1 pro-inflammatory cytokines. Additional data from head-to-head studies between eblasakimab and dupilumab in skin biopsies from AD patients confirmed the differentiated effects of targeting IL-13R versus IL-4R5.

与IL-4R阻断相比，IL-13R阻断导致涉及2型驱动（过敏）炎症的细胞因子的更有效减少，以及1型促炎细胞因子的较低水平。来自AD患者皮肤活检中eblasakimab和dupilumab之间的头对头研究的其他数据证实了靶向IL-13R与IL-4R5的不同作用。

In this study, eblasakimab reduced localized secretion of pro-inflammatory Type 2 cytokines by the skin tissue more efficiently than dupilumab, suggesting eblasakimab could have the potential to be effective in AD patients that do not achieve an adequate response to dupilumab. .

在这项研究中，eblasakimab比dupilumab更有效地减少了皮肤组织促炎性2型细胞因子的局部分泌，这表明eblasakimab可能对未对dupilumab产生足够反应的AD患者有效。

References

参考文献

Decision Resources Group (2023) Atopic Dermatitis Disease Landscape and Forecast Report

决策资源小组（2023）特应性皮炎疾病概况和预测报告

Thaci et al (2019) J Dermatol Sci 94(2):266-275

Thaci等人（2019）皮肤科杂志94（2）：266-275

Worm et al (2020) JAMA Derm 156(2):131-143

Worm等人（2020）JAMA Derm 156（2）：131-143

Cevikbas et al (2023) 1st International Society of Investigative Dermatology Meeting, May 10-14, 2023

Cevikbas等人（2023年）第一届国际皮肤病研究学会会议，2023年5月10日至14日

Cevikbas et al (2023) 7th Annual Dermatology Drug Development Summit, October 31-November 2, 2023

Cevikbas等人（2023）第七届年度皮肤病药物开发峰会，2023年10月31日至11月2日

About TREK-DX

关于TREK-DX

TREK-DX trial is a randomized, double-blind, placebo-controlled, multicenter trial to evaluate the efficacy and safety of eblasakimab in patients with moderate-to-severe AD previously treated with dupilumab. The trial will enroll approximately 75 patients who have discontinued dupilumab treatment for any reason, including inadequate control of AD, loss of access or an adverse event.

TREK-DX试验是一项随机，双盲，安慰剂对照的多中心试验，用于评估先前接受dupilumab治疗的中度至重度AD患者中eblasakimab的疗效和安全性。该试验将招募约75名因任何原因停止dupilumab治疗的患者，包括AD控制不足，无法进入或不良事件。

The trial consists of a 16-week treatment period and an 8-week safety follow-up period. The primary efficacy endpoint is percentage change in Eczema Area Severity Index (EASI) score from baseline to week 16. Key secondary efficacy endpoints include the proportion of patients achieving validated Investigator Global Assessment (vIGA) score of 0 (clear) or 1 (almost clear), proportion of patients with a 75% or greater reduction in EASI (EASI-75), proportion of patients achieving EASI-50 and EASI-90, and changes in peak pruritus..

该试验包括16周的治疗期和8周的安全随访期。主要疗效终点是湿疹面积严重程度指数（EASI）评分从基线到第16周的百分比变化。关键的次要疗效终点包括达到经过验证的研究者全球评估（vIGA）评分为0（清晰）或1（几乎清晰）的患者比例，EASI降低75%或更高的患者比例（EASI-75），达到EASI-50和EASI-90的患者比例，以及瘙痒峰值的变化。。

About eblasakimab

版权所有（c）输电项目

Eblasakimab is a potential first-in-class monoclonal antibody targeting the IL-13 receptor subunit of the Type 2 receptor, a key pathway driving several allergic inflammatory diseases. Eblasakimab’s unique mechanism of action enables specific blockade of the Type 2 receptor and has the potential to improve upon current biologics used to treat allergic disease.

Eblasakimab是一种潜在的一流单克隆抗体，靶向2型受体的IL-13受体亚基，这是驱动几种过敏性炎症疾病的关键途径。Eblasakimab独特的作用机制能够特异性阻断2型受体，并有可能改善目前用于治疗过敏性疾病的生物制剂。

By blocking the Type 2 receptor, eblasakimab prevents signaling through both interleukin 4 (IL-4) and interleukin 13 (IL-13) – the key drivers of inflammation in AD and Type 2 driven COPD. Positive results from the Phase 2b TREK-AD study in moderate-to-severe AD support eblasakimab’s potential to deliver a monthly dosing regimen from initiation in AD without compromising on efficacy and with an encouraging safety profile demonstrated to date, with preparations for Phase 3 underway.

通过阻断2型受体，eblasakimab阻止通过白细胞介素4（IL-4）和白细胞介素13（IL-13）发出信号，白细胞介素4和白细胞介素13是AD和2型驱动的COPD炎症的关键驱动因素。中度至重度AD的2b期TREK-AD研究的阳性结果支持了eblasakimab从AD开始提供每月给药方案的潜力，而不影响疗效，并且迄今为止已证明具有令人鼓舞的安全性，正在进行第3阶段的准备工作。

ASLAN is also investigating eblasakimab in dupilumab experienced, moderate-to-severe AD patients in the Phase 2 TREK-DX study..

ASLAN还在2期TREK-DX研究中研究了dupilumab经验丰富的中重度AD患者中的eblasakimab。。

About ASLAN Pharmaceuticals

关于阿斯兰制药

ASLAN Pharmaceuticals (Nasdaq: ASLN) is a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients. ASLAN is developing eblasakimab, a potential first-in-class antibody targeting the IL-13 receptor in moderate-to-severe atopic dermatitis (AD) with the potential to improve upon current biologics used to treat allergic disease, and has reported positive topline data from a Phase 2b, dose-ranging study in moderate-to-severe AD patients.

ASLAN Pharmaceuticals（纳斯达克：ASLN）是一家临床阶段，以免疫学为重点的生物制药公司，开发创新疗法以改变患者的生活。阿斯兰正在开发eblasakimab，这是一种针对中重度特应性皮炎（AD）中IL-13受体的潜在一流抗体，有可能改善目前用于治疗过敏性疾病的生物制剂，并报告了来自2b期的阳性topline数据，中重度AD患者的剂量范围研究。

ASLAN is also investigating eblasakimab in dupilumab experienced, moderate-to-severe AD patients in the Phase 2 TREK-DX study with a topline data readout expected at the end of 2024. Farudodstat, a potent oral inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH), is being developed by ASLAN as a potential first-in-class treatment for alopecia areata (AA) in a Phase 2a, proof-of-concept trial with an interim readout expected in mid-2024.

ASLAN还在第二阶段TREK-DX研究中研究了在dupilumab经验丰富的中度至重度AD患者中使用eblasakimab的情况，预计2024年底将进行topline数据读取。阿斯兰正在开发一种有效的二氢乳清酸脱氢酶（DHODH）口服抑制剂Farudodstat，作为2a期概念验证试验中斑秃（AA）的潜在一流治疗方法，预计将于2024年年中进行临时读数。

ASLAN has teams in San Mateo, California, and in Singapore. For additional information please visit ASLAN’s website or follow ASLAN on LinkedIn..

阿斯兰在加利福尼亚州圣马特奥和新加坡都有团队。有关更多信息，请访问ASLAN的网站或在LinkedIn上关注ASLAN。。

Forward-looking statements

前瞻性声明

This release contains forward-looking statements. These statements are based on the current beliefs and expectations of the management of ASLAN Pharmaceuticals Limited and/or its affiliates (the 'Company'). These forward-looking statements may include, but are not limited to statements regarding the Company’s business strategy and clinical development plans; the Company’s plans to develop and commercialize eblasakimab; statements related to the safety and efficacy of eblasakimab, including preliminary blinded data; the Company’s plans and expected timing with respect to manufacturing activities, clinical trials, clinical trial enrolment and clinical trial results for eblasakimab; and the potential of eblasakimab as a first-in-class treatment for atopic dermatitis.

本版本包含前瞻性声明。这些声明基于阿斯兰制药有限公司和/或其附属公司（“公司”）管理层目前的信念和期望。这些前瞻性声明可能包括但不限于有关公司业务战略和临床发展计划的声明；该公司计划开发和商业化eblasakimab；有关eblasakimab安全性和有效性的声明，包括初步盲法数据；公司关于eblasakimab的生产活动，临床试验，临床试验注册和临床试验结果的计划和预期时间；以及eblasakimab作为特应性皮炎的一流治疗方法的潜力。

The Company’s estimates, projections and other forward-looking statements are based on management's current assumptions and expectations of future events and trends, which affect or may affect the Company’s business, strategy, operations, or financial performance, and inherently involve significant known and unknown risks and uncertainties.

公司的估计、预测和其他前瞻性报表基于管理层对未来事件和趋势的当前假设和预期，这些事件和趋势会影响或可能影响公司的业务、战略、运营或财务业绩，并且固有地涉及重大的已知和未知风险和不确定性。

Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of many risks and uncertainties, which include, unexpected safety or efficacy data observed during preclinical or clinical studies; risks that future clinical trial results may not be consistent with interim, initial or preliminary results or results from prior preclinical studies or clinical trials; risks that trends or characteristics based on preliminary blinded data may not be consistent with unblinded data; clinical site activation rates or clinical trial enrolment rates that are lower than expected; the impact of geopolitical conflicts .

由于许多风险和不确定性，包括在临床前或临床研究期间观察到的意外安全性或有效性数据，实际结果和事件发生的时间可能与此类前瞻性声明中预期的结果存在重大差异；未来临床试验结果可能与中期，初始或初步结果或先前临床前研究或临床试验结果不一致的风险；基于初步盲法数据的趋势或特征可能与非盲法数据不一致的风险；临床现场激活率或临床试验入学率低于预期；地缘政治冲突的影响。

ASLAN Media and IR contacts

ASLAN Media和IR联系人

Emma Thompson

艾玛·汤普森

Spurwing Communications

刺激通信

Tel: +65 6206 7350

电话：+65 6206 7350

Email: ASLAN@spurwingcomms.com

电子邮件ASLAN@spurwingcomms.com

Ashley R. Robinson

阿什利·R·罗宾逊

LifeSci Advisors, LLC

LifeSci Advisors有限责任公司

Tel: +1 (617) 430-7577

电话：+1（617）430-7577

Email: arr@lifesciadvisors.com

电子邮件arr@lifesciadvisors.com