Positive Topline Data from the Fourth Cohort of Patients

第四组患者积极的总体数据

Consistent demonstration of polycystin (PC) biomarker impact confirming 300 mg fixed dose selection to achieve optimal kidney exposure

持续展示多囊蛋白（PC）生物标志物的影响，确认选择300毫克固定剂量以实现最佳的肾脏暴露。

Patients receiving 300 mg farabursen demonstrated a mean halting of height-adjusted total kidney volume (htTKV) growth over 4 months

接受300毫克farabursen治疗的患者在4个月内显示出身高调整后的总肾体积（htTKV）增长平均停止。

Exploratory analysis of patients from high-dose cohorts demonstrates statistical significance in htTKV change compared to a large cohort of historical placebo-treated patients, which meaningfully derisks the 12-month htTKV endpoint in the planned Phase 3 trial

对高剂量队列患者的探索性分析显示，与大量历史安慰剂治疗患者相比，htTKV变化具有统计学意义，这有效地降低了计划中的III期试验中12个月htTKV终点的风险。

Company on track for initiation of Phase 3 single pivotal trial in third quarter 2025

公司有望在2025年第三季度启动第三阶段单个关键试验

SAN DIEGO

圣地亚哥

,

，

March 27, 2025

2025年3月27日

/PRNewswire/ -- Regulus Therapeutics Inc. (Nasdaq:

/PRNewswire/ -- Regulus Therapeutics Inc.（纳斯达克：

RGLS

RGLS

), a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs (the 'Company' or 'Regulus'), today announced positive topline results from all patients in the fourth cohort in its Phase

），一家专注于发现和开发针对微小RNA的创新药物的生物制药公司（“公司”或“Regulus”），今天宣布了其第四阶段试验中第四组所有患者的积极顶线结果。

1b

1b

MAD study of farabursen for the treatment of ADPKD.

MAD研究法拉布森治疗ADPKD。

The Phase 1b MAD study is a double-blind, placebo-controlled trial which evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of farabursen in adult patients with ADPKD. The study evaluated farabursen treatment for three months followed by one month of follow up across three weight-based dose levels (1, 2 and 3 mg/kg) and one fixed dose level (300 mg).

第1b阶段的多剂量递增（MAD）研究是一项双盲、安慰剂对照试验，评估了farabursen在成人ADPKD患者中的安全性、耐受性、药代动力学和药效学（PK/PD）。该研究评估了farabursen治疗三个月的效果，并在三个基于体重的剂量水平（1、2和3 mg/kg）以及一个固定剂量水平（300 mg）下进行了一个月的随访。

Primary endpoints were changes in urinary PC1 and PC2, with an exploratory examination of change in htTKV growth rate. PC1 and PC2 are the protein products of the PKD1 and PKD2 genes and their levels have been shown to inversely correlate with disease severity; htTKV has been shown to inversely correlate with kidney function..

主要终点是尿液中PC1和PC2的变化，并对htTKV增长率的变化进行探索性检查。PC1和PC2是PKD1和PKD2基因的蛋白质产物，其水平已被证明与疾病严重程度呈负相关；htTKV已被证明与肾功能呈负相关。

In the fourth cohort, 26 subjects received a fixed dose of 300 mg of farabursen every other week for three months.  Consistent with the previously announced interim analysis of efficacy data from the first 14 subjects of this fixed-dose cohort, the full cohort of 26 patients demonstrated similar mechanistic response based on urinary PC1 and PC2 levels as well as a mean halting of htTKV growth over the four-month study period..

在第四组队列中，26名受试者每隔一周接受固定剂量300毫克的法拉布森治疗，持续三个月。与此前公布的该固定剂量队列前14名受试者的中期疗效数据分析一致，全部26名患者在整个四个月的研究期间，基于尿液PC1和PC2水平表现出相似的机制反应，并且htTKV增长平均停止。

Cohort 4 data highlights:

第四批数据亮点：

Increases in urinary PC1 and PC2 levels were similar to cohort 3 and reached a similar level of statistical significance compared to placebo (PC1 p=0.026; PC2 p=0.014).

尿液中 PC1 和 PC2 水平的升高与队列 3 相似，并且与安慰剂相比达到了相似的统计学显著性水平（PC1 p=0.026；PC2 p=0.014）。

Mean htTKV growth rate over 4 months was 0.05% (SE -0.86% to +0.92%) while placebo subjects in the trial experienced a mean growth rate of 2.58% (SE +1.09% to +4.10%).

4个月内的平均htTKV增长率为0.05%（标准误 -0.86% 至 +0.92%），而试验中安慰剂组的平均增长率为2.58%（标准误 +1.09% 至 +4.10%）。

Changes in htTKV were highly correlated with changes in renal cyst volume, suggesting farabursen directly impacts disease progression by limiting abnormal cyst growth.

htTKV的变化与肾囊肿体积的变化高度相关，这表明farabursen通过限制异常囊肿生长直接影响疾病进展。

In an exploratory analysis, the combination of patients treated with 3 mg/kg or 300 mg fixed dose farabursen (n=35) were compared to a combined historical control group of placebo-treated patients from prior pivotal ADPKD trials (n=550). Farabursen-treated patients experienced mean reduction in htTKV growth rate (-0.14%) compared to a mean increase of (+1.87%) in placebo-treated patients (p=0.0056)..

在一项探索性分析中，将接受3 mg/kg或300 mg固定剂量法巴昔单抗治疗的患者（n=35）与来自先前关键ADPKD试验的安慰剂治疗患者的历史对照组（n=550）进行了比较。法巴昔单抗治疗的患者平均htTKV增长率减少了（-0.14%），而安慰剂治疗的患者平均增加了（+1.87%）（p=0.0056）。

Farabursen at 300 mg demonstrated a favorable safety and tolerability profile in this study, consistent with earlier cohorts.

在本研究中，300毫克的Farabursen显示出良好的安全性和耐受性，与早期队列一致。

'We are pleased that the results of cohort 4 demonstrate a level of mechanistic response, as measured by urinary PC1 and PC2, that indicates maximal anti-miR-17 activity. Along with the observed favorable safety and tolerability profile, these results give us confidence that 300 mg provides optimal target exposure and is the appropriate dose to take forward into Phase 3,' said .

“我们很高兴队列4的结果表明，通过尿液PC1和PC2测量的机制反应水平达到了最大抗miR-17活性。结合观察到的良好安全性和耐受性特征，这些结果使我们相信300毫克能够提供最佳的目标暴露量，并且是推进到第三阶段的合适剂量，”研究人员表示。

Preston Klassen

普雷斯顿·克拉森

, M.D., President and Head of Research & Development of Regulus Therapeutics. 'Even more encouraging is the repeated demonstration across multiple cohorts in the trial that, on average, growth of the kidney in ADPKD patients is halted after only a relatively short treatment period with farabursen. Based on exploratory analysis of Cohorts 3 & 4, which deliver overlapping drug exposures, we are confident that the htTKV effects seen with farabursen in this trial are clinically meaningful and provide important insight into the probability of success for the 12-month htTKV endpoint in the planned Phase 3 trial.'.

，医学博士，Regulus Therapeutics公司总裁兼研发部门负责人。“更令人鼓舞的是，试验中多个队列反复显示，ADPKD患者的肾脏生长在经过相对短暂的farabursen治疗后平均得以停止。基于对第3和第4队列（提供重叠的药物暴露）的探索性分析，我们相信farabursen在此试验中表现出的htTKV效应具有临床意义，并为计划中的III期试验12个月htTKV终点的成功概率提供了重要见解。”

'With full data from cohort 4 now analyzed, we are pleased with the positive results, in line with our expectations based on previous cohorts. These data suggest that farabursen has the potential to be an important addition to the limited therapeutic options for patients with ADPKD,' said

“随着第4组完整数据的分析完成，我们对这一积极结果感到满意，这与我们基于之前组别的预期相符。这些数据表明，法拉贝森有望成为ADPKD患者有限治疗选择中的重要补充。”

Jay Hagan

杰伊·哈根

, CEO of Regulus Therapeutics. 'I would like to thank all the patients, physicians, and support staff who have been vital to the ongoing development of farabursen. We are excited to move forward with initiation of the pivotal Phase 3 trial later this year.'

Regulus Therapeutics首席执行官表示：“我要感谢所有对farabursen的持续开发起到重要作用的患者、医生和支持人员。我们很高兴在今年晚些时候启动关键的第三阶段试验。”

In January, the Company announced that it held a meeting with U.S. Food and Drug Administration (FDA) and had confirmed alignment with the FDA on the acceptability of the program's CMC, non-clinical and clinical pharmacology plans and the key elements of a Phase 3 trial design as a single pivotal study, including a 12-month htTKV endpoint planned to support Accelerated Approval and a 24-month eGFR endpoint to support Full Approval..

今年1月，公司宣布与美国食品药品监督管理局（FDA）举行会议，确认就项目的CMC、非临床和临床药理学计划以及作为单一关键研究的III期试验设计的关键要素与FDA达成一致，其中包括计划支持加速批准的12个月htTKV终点，以及支持完全批准的24个月eGFR终点。

More information about the MAD clinical trial is available at clinicaltrials.gov (

有关MAD临床试验的更多信息，请访问clinicaltrials.gov (

NCT05521191

NCT05521191

).

）。

About ADPKD

关于ADPKD

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in the PKD1 or PKD2 genes, is among the most common human monogenic disorders and a leading cause of end-stage renal disease. The disease is characterized by the development of multiple fluid filled cysts primarily in the kidneys, and to a lesser extent in the liver and other organs.

常染色体显性多囊肾病 (ADPKD) 由 PKD1 或 PKD2 基因突变引起，是人类最常见的单基因遗传疾病之一，也是终末期肾病的主要原因之一。该疾病的特点是主要在肾脏，其次在肝脏和其他器官中形成多个充满液体的囊肿。

Excessive kidney cyst cell proliferation, a central pathological feature, ultimately leads to end-stage renal disease in approximately 50% of ADPKD patients by age 60. Approximately 160,000 individuals are diagnosed with the disease in .

过度的肾囊肿细胞增殖作为一个核心病理特征，最终会导致大约50%的ADPKD患者在60岁前发展为终末期肾病。约有16万人被诊断出患有此疾病。

the United States

美国

alone, with an estimated global prevalence of 4 to 7 million.

alone，全球患病率估计为400万至700万。

About Farabursen (RGLS8429)

关于法拉布尔森 (RGLS8429)

Farabursen is a novel, next generation oligonucleotide for the treatment of ADPKD designed to inhibit miR-17 and to preferentially target the kidney. Administration of farabursen has shown clear improvements in kidney function, size, and other measures of disease severity in preclinical models. Regulus announced completion of the Phase 1 SAD study in .

Farabursen是一种新型的下一代寡核苷酸，用于治疗ADPKD，旨在抑制miR-17并优先靶向肾脏。在临床前模型中，Farabursen的使用已显示出肾功能、大小和其他疾病严重程度指标的显著改善。Regulus宣布完成了1期单次递增剂量（SAD）研究。

September 2022

2022年9月

. The Phase 1 SAD study demonstrated that farabursen has a favorable safety and PK profile. Farabursen was well-tolerated with no serious adverse events reported and plasma exposure was approximately linear across the four doses tested. In the Phase

第一阶段的单剂量递增（SAD）研究显示，farabursen 具有良好的安全性和药代动力学特性。Farabursen 耐受性良好，未报告严重不良事件，且在测试的四个剂量下血浆暴露量近似呈线性。在第二阶段

1b

1b

MAD study, Regulus announced topline data from the first cohort of patients in

MAD研究，Regulus宣布了第一组患者队列的初步数据。

September 2023

2023年9月

, from the second cohort of patients in

，来自第二批患者中的

March 2024

2024年3月

, from the third cohort of patients in

，来自第三批患者

June 2024

2024年6月

, and from the fourth cohort in

，以及来自第四队列的

March 2025

2025年3月

. Patients in the fourth cohort received an open-label 300 mg fixed dose of farabursen which was administered every other week for three months. Review of complete safety data from all cohorts demonstrated that farabursen was well tolerated.

第四组患者接受开放标签的300毫克固定剂量的法拉布森，每两周给药一次，持续三个月。对所有组的安全数据进行全面审查后表明，法拉布森具有良好的耐受性。

About Regulus

关于Regulus

Regulus Therapeutics Inc. (Nasdaq:

Regulus Therapeutics Inc.（纳斯达克：

RGLS

RGLS

) is a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs. Regulus has leveraged its oligonucleotide drug discovery and development expertise to develop a pipeline complemented by a rich intellectual property estate in the microRNA field. Regulus maintains its corporate headquarters in .

）是一家专注于发现和开发针对微小RNA的创新药物的生物制药公司。Regulus利用其寡核苷酸药物发现和开发的专业知识，建立了一个由丰富的微小RNA领域知识产权资产支持的研发管线。Regulus的公司总部设在。

San Diego, CA.

加利福尼亚州圣迭戈。

Forward-Looking Statements

前瞻性声明

Statements contained in this press release regarding matters that are not historical facts are 'forward-looking statements' within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with the Company's farabursen (RGLS8429) program, the potential that farabursen may be eligible for an Accelerated Approval pathway, predictions based on and future results and clinical outcomes suggested by the Cohort 4 data, our Phase 3 trial design including whether the selected fixed dose will be efficacious or whether the FDA will ultimately determine its components and the overall design to be acceptable and sufficient to serve as a single pivotal study, planned data announcements and, the timing and future occurrence of other preclinical and clinical activities.

本新闻稿中包含的关于非历史事实事项的陈述符合1995年《私人证券诉讼改革法案》中定义的“前瞻性陈述”，包括与公司farabursen（RGLS8429）项目相关的陈述、farabursen可能符合加速批准路径的潜力、基于第四组数据的预测及未来结果和临床结果、我们的三期试验设计（包括所选固定剂量是否有效或FDA最终是否会认定其组成部分及整体设计可接受并足以作为单一关键研究）、计划中的数据发布以及其它临床前和临床活动的时间安排与未来进展。

Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as 'confident,' 'expectations,' 'on track,' 'plans,' 'probability,'  'potential,' 'suggest,' and similar expressions are intended to identify forward-looking statements.

由于此类声明受到风险和不确定性的约束，实际结果可能与这些前瞻性声明所表达或暗示的结果有重大差异。诸如“有信心”、“预期”、“按计划”、“计划”、“可能性”、“潜力”、“表明”等词语及类似表述旨在识别前瞻性声明。

These forward-looking statements are based upon Regulus' current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation: the risk that the approach we are taking to discover and develop drugs is novel and may never lead to marketable products; preliminary or topline results are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive.

这些前瞻性陈述基于 Regulus 的当前预期，并涉及可能永远不会实现或可能被证明是不正确的假设。由于各种风险和不确定性，实际结果和事件的时间安排可能会与这些前瞻性陈述中预期的情况大相径庭，其中包括（但不限于）以下风险：我们用于发现和开发药物的方法是新颖的，可能永远不会带来可上市的产品；初步或顶级结果基于对关键疗效和安全数据的初步分析，而这些数据在更全面的分析后可能会发生变化。

www.sec.gov

www.sec.gov

. All forward-looking statements contained in this press release speak only as of the date on which they were made. Regulus undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

本新闻稿中包含的所有前瞻性陈述仅在其作出之日有效。Regulus 没有义务更新这些陈述以反映在其作出之日后发生的事件或存在的状况。

SOURCE Regulus Therapeutics Inc.

来源：Regulus Therapeutics Inc.

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