PASADENA, Calif.--(BUSINESS WIRE)--Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that new interim clinical data on ARO-RAGE, an investigational RNAi-based medicine for the treatment of inflammatory lung diseases, such as asthma, were presented at the American Thoracic Society (ATS) 2024 International Conference.

加利福尼亚州帕萨迪纳（商业新闻短讯）--箭头制药公司（NASDAQ:ARWR）今天宣布，ARO-RAGE是一种基于rna干扰的研究性药物，用于治疗哮喘等炎症性肺病，其新的临时临床数据已在美国胸科学会（ATS）2024年国际会议上发表。

Interim results from the ongoing Phase 1/2 study demonstrate that treatment with ARO-RAGE led to a reduction in soluble RAGE (sRAGE) concentration in bronchoalveolar lavage fluid (BALF) and serum in a dose-dependent manner in normal healthy volunteers (NHV) and in patients with mild to moderate asthma..

正在进行的1/2期研究的中期结果表明，在正常健康志愿者（NHV）和轻度至中度哮喘患者中，ARO-RAGE治疗导致支气管肺泡灌洗液（BALF）和血清中可溶性RAGE（sRAGE）浓度呈剂量依赖性降低。。

“These results underscore the potential of our proprietary TRiMTM platform to enable us to develop impactful new therapies to potentially treat multiple pulmonary diseases with significant unmet needs. Arrowhead was the first company to show that RNAi could be harnessed to achieve high levels of target gene knockdown in the lung in healthy human subjects and these data presented at ATS 2024 build on that success,” said James Hamilton, M.D., chief of discovery and translational medicine at Arrowhead.

“这些结果突显了我们专有的TRiMTM平台的潜力，使我们能够开发出有影响力的新疗法，以潜在地治疗多种肺部疾病，这些疾病的需求尚未得到满足。Arrowhead是第一家证明可以利用RNAi在健康人类受试者的肺部实现高水平靶基因敲除的公司，这些在ATS 2024上提供的数据建立在这一成功的基础上，”Arrowhead的发现和转化医学主任詹姆斯·汉密尔顿医学博士说。

“Our ARO-RAGE data is first-in-class and demonstrated deep and sustained knockdown in the lung in patients with mild to moderate asthma, a long duration of effect that appears to support every two-month dosing, and a favorable safety and tolerability profile. These results give us further confidence as we move towards the initiation of a Phase 2 study in late 2024.”.

“我们的ARO-RAGE数据是一流的，显示轻度至中度哮喘患者的肺部深度持续敲低，持续时间长，似乎支持每两个月一次的剂量，并且具有良好的安全性和耐受性。随着我们在2024年底开始第二阶段研究，这些结果给了我们进一步的信心。”。

Select ARO-RAGE Results

选择ARO-RAGE结果

In the ongoing 1001 study, ARO-RAGE achieved the following key results as of 05 April 2024:

在正在进行的1001研究中，截至2024年4月5日，ARO-RAGE取得了以下关键成果：

Single and multiple doses of ARO-RAGE in NHVs led to dose dependent reductions in sRAGE in both BALF and in serum

NHV中单剂量和多剂量的ARO-RAGE导致BALF和血清中sRAGE的剂量依赖性降低

After two doses of ARO-RAGE in patients with mild to moderate asthma, serum sRAGE was reduced up to 88% with a mean maximum reduction up to 77%

轻度至中度哮喘患者服用两剂ARO-RAGE后，血清sRAGE降低至88%，平均最大降低至77%

Serum sRAGE was reduced in a dose-responsive manner with similar reductions observed in NHVs and patients with asthma at each dose level

血清sRAGE以剂量反应性方式降低，在每个剂量水平的NHV和哮喘患者中观察到类似的降低

Pharmacodynamic effects were long lasting, with a duration that appears to support once every two-month dosing

药效学作用持久，持续时间似乎支持每两个月一次给药

ARO-RAGE plasma exposure following a single dose in NHVs was of limited quantity and duration

在NHV中单次剂量后ARO-RAGE血浆暴露的数量和持续时间有限

Safety and Tolerability Results

安全性和耐受性结果

ARO-RAGE has shown a favorable safety profile to date, with no demonstrated pattern of effect on systemic safety labs and no demonstrated pattern of detrimental effect on lung function (FEV1, FVC, or DLCO) over time. There have been no serious adverse effects related to study drug and no treatment emergent adverse events leading to trial withdrawal or study drug discontinuation..

迄今为止，ARO-RAGE已显示出良好的安全性，随着时间的推移，没有显示出对全身安全实验室的影响模式，也没有显示出对肺功能（FEV1，FVC或DLCO）有害影响的模式。没有与研究药物相关的严重不良反应，也没有导致试验停药或研究药物停药的治疗紧急不良事件。。

Arrowhead also presented preclinical data on two additional lung targeted programs that utilize the company’s proprietary Targeted RNAi Molecule (TRiMTM) platform. ARO-TSLP is designed to silence the epithelial cytokine thymic stromal lymphopoietin (TSLP), a genetically and clinically validated therapeutic target that activates multiple immune cell lineages to promote asthmatic inflammation.

箭头还介绍了另外两个利用该公司专有靶向RNAi分子（TRiMTM）平台的肺靶向计划的临床前数据。ARO-TSLP旨在沉默上皮细胞因子胸腺基质淋巴细胞生成素（TSLP），TSLP是一种经过遗传和临床验证的治疗靶点，可激活多种免疫细胞谱系以促进哮喘炎症。

ARO-IAV is designed to silence expression of highly conserved influenza A viruses, including the highly pathogenic avian influenza virus (H5N1)..

ARO-IAV旨在沉默高度保守的甲型流感病毒的表达，包括高致病性禽流感病毒（H5N1）。。

Details about the ATS presentations are listed below.

ATS演示的详细信息如下所示。

American Thoracic Society (ATS) 2024 International Conference – May 17-22, 2024

美国胸科学会（ATS）2024年国际会议–2024年5月17日至22日

Title: A First-in-Human Study of ARO-RAGE, a Novel Inhaled RNA-Interference Therapy for Asthma

标题：ARO-RAGE的首次人体研究，ARO-RAGE是一种治疗哮喘的新型吸入RNA干扰疗法

Date/Time: May 19, 2024, 11:30 a.m. PDT

日期/时间：2024年5月19日太平洋时间上午11:30

Type: Late-Breaking Poster

类型：迟发海报

Title: A lung-targeted therapeutic siRNA against highly conserved viral M1 mRNAs effectively limits highly pathogenic influenza A infection in mice

标题：针对高度保守的病毒M1 mRNA的肺靶向治疗性siRNA有效限制了小鼠的高致病性甲型流感感染

Date/Time: May 20, 2024, 11:30 a.m. PDT

日期/时间：2024年5月20日太平洋时间上午11:30

Type: Poster

类型：海报

Title: Lung-targeted RNAi molecules silence human TSLP expression in PCLS cultures and humanized mice and suppress pulmonary allergic inflammation

标题：肺靶向RNAi分子沉默PCLS培养物和人源化小鼠中人TSLP的表达，并抑制肺部过敏性炎症

Date/Time: May 20, 2024, 11:30 a.m. PDT

日期/时间：2024年5月20日太平洋时间上午11:30

Type: Poster

类型：海报

Presentation materials may be accessed on the Events and Presentations page in the Investors section of the Arrowhead website.

演示材料可以在箭头网站投资者部分的活动和演示页面上访问。

About Pulmonary TRiMTM Platform

关于肺部TRiMTM平台

Arrowhead’s pulmonary Targeted RNAi Molecule (TRiMTM) delivery platform facilitates selective delivery of therapeutic small interfering RNAs (siRNAs) to the lung epithelium via an integrin αvβ6 targeting moiety, mediating durable gene silencing upon inhalation utilizing a nebulizer.

Arrowhead的肺靶向RNAi分子（TRiMTM）递送平台有助于通过整联蛋白αvβ6靶向部分选择性地将治疗性小干扰RNA（siRNA）递送至肺上皮，从而在使用雾化器吸入时介导持久的基因沉默。

About ARO-RAGE

关于ARO-RAGE

ARO-RAGE is an investigational RNAi therapeutic targeting the receptor for advanced glycation end-products (RAGE) as a potential treatment for inflammatory lung diseases. RAGE is implicated as an upstream mediator of Type-2 and non-Type-2 inflammatory cascades and is involved in the pathogenesis of asthma and numerous inflammatory diseases1,2,3.

ARO-RAGE是一种研究性RNAi治疗剂，靶向晚期糖基化终产物（RAGE）受体，作为炎症性肺病的潜在治疗方法。RAGE被认为是2型和非2型炎症级联反应的上游介质，并参与哮喘和许多炎症性疾病的发病机制1,2,3。

Silencing RAGE expression via RNAi is designed to reduce the amount of RAGE protein expressed on pulmonary epithelial cells. Reduced RAGE expression in the pulmonary epithelium may result in reduction of RAGE-dependent inflammatory pathways, leading to decreased exacerbation frequency and improved airflow in patients with asthma..

通过RNAi沉默RAGE表达旨在减少肺上皮细胞上表达的RAGE蛋白的量。肺上皮中RAGE表达的降低可能导致RAGE依赖性炎症途径的减少，导致哮喘患者的恶化频率降低和气流改善。。

About the ARORAGE-1001 Phase 1/2 Study

关于ARORAGE-1001 1/2期研究

ARORAGE-1001 (NCT05276570) is an ongoing Phase 1/2a, randomized, double-blinded, placebo-controlled study in normal healthy volunteers (NHV) (Part 1), in patients with mild to moderate asthma (Part 2), and in patients with high baseline fractional exhaled nitric oxide (FeNO) (Part 3). Subjects receive ascending doses of ARO-RAGE or placebo via nebulizer on Day 1 in the single-ascending dose cohorts or Days 1 and 29 in the multiple-ascending dose cohorts.

ARORAGE-1001（NCT05276570）是一项正在进行的1/2a期，随机，双盲，安慰剂对照研究，研究对象为正常健康志愿者（NHV）（第1部分），轻度至中度哮喘患者（第2部分），以及基线呼出气一氧化氮（FeNO）分数高的患者（第3部分）。受试者在单次递增剂量组的第1天或多次递增剂量组的第1天和第29天通过雾化器接受递增剂量的ARO-RAGE或安慰剂。

The objectives of the study include the assessment of safety and tolerability, pharmacokinetics, and pharmacodynamics of ARO-RAGE in NHVs and patients with asthma..

该研究的目的包括评估ARO-RAGE在NHV和哮喘患者中的安全性和耐受性，药代动力学和药效学。。

About Arrowhead Pharmaceuticals

关于箭头制药

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes.

箭头制药公司（Arrowhead Pharmaceuticals）通过沉默导致顽固性疾病的基因来开发治疗顽固性疾病的药物。使用广泛的RNA化学组合和有效的递送方式，箭头疗法触发RNA干扰机制，以诱导靶基因的快速，深入和持久的敲低。

RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing..

RNA干扰（RNAi）是活细胞中存在的一种机制，可抑制特定基因的表达，从而影响特定蛋白质的产生。Arrowhead基于RNAi的疗法利用了这种基因沉默的自然途径。。

For more information, please visit www.arrowheadpharma.com, or follow us on X (formerly Twitter) at @ArrowheadPharma or on LinkedIn. To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts.

有关更多信息，请访问www.arrowheadharma.com，或通过X（以前的推特）关注我们@arrowheadharma或LinkedIn。要添加到公司的电子邮件列表并直接接收新闻，请访问http://ir.arrowheadpharma.com/email-alerts.

Safe Harbor Statement under the Private Securities Litigation Reform Act:

私人证券诉讼改革法案下的安全港声明：

This news release contains forward-looking statements within the meaning of the 'safe harbor' provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as “may,” “will,” “expect,” “believe,” “anticipate,” “hope,” “intend,” “plan,” “project,” “could,” “estimate,” “continue,” “target,” “forecast” or “continue” or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements.

本新闻稿包含1995年《私人证券诉讼改革法案》中“安全港”条款所指的前瞻性声明。除历史信息外，本版本中包含的任何声明都可能被视为前瞻性声明。在不限制上述一般性的情况下，诸如“可能”、“将”、“预期”、“相信”、“预期”、“希望”、“打算”、“计划”、“项目”、“可能”、“估计”、“继续”、“目标”、“预测”或“继续”等词语或其其他变体或类似术语的否定词旨在识别此类前瞻性陈述。

In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements.

此外，任何涉及我们未来财务业绩预测、业务趋势、对我们产品线或候选产品的期望（包括预期的监管提交和临床计划结果）、我们与其他公司合作的前景或益处，或未来事件或情况的其他特征的声明都是前瞻性声明。

These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions we have entered into or may enter into in the future; our beliefs and expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties.

这些前瞻性陈述包括但不限于关于我们的临床前研究和临床试验以及我们的研究和开发计划的开始，时间，进展和结果的陈述；我们对合作伙伴关系、许可和/或合作安排以及我们已经达成或将来可能达成的其他战略安排和交易的潜在利益的期望；我们对里程碑、特许权使用费或现有协议下可能应付给第三方或来自第三方的其他付款的信念和期望；以及我们对未来收入、研发费用、资本要求和向第三方付款的估计。

These statements are based u.

这些声明基于美国。

Source: Arrowhead Pharmaceuticals, Inc.

来源：Arrowhead Pharmaceuticals，Inc。

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1.

1.

Perkins TN. Allergy 2021;76:1350-66.

Perkins TN.过敏2021；76:1350年至1356年。

2.

2.

Oczypok EA. JACI 2015;136:747-56.

EA挂钩。JACI 2015；136:747-56.

3.

3.

Killian KN. Front Immunol 2023;14:1039997.

Killian KN。前免疫2023；14： 1039997年。