Continued mechanistic dose response observed following completion of 3 mg/kg dose level based on urinary biomarker analyses

根据尿液生物标志物分析，在完成3 mg/kg剂量水平后观察到持续的机械剂量反应

Percent change from baseline in PC1 and PC2 demonstrated a dose response across all doses tested, with statistical significance seen at 3 mg/kg compared to placebo

PC1和PC2与基线相比的百分比变化表明，所有测试剂量均存在剂量反应，与安慰剂相比，在3 mg/kg时具有统计学意义

Exploratory imaging analyses indicated reduction in total kidney volume in 70% of patients dosed with 3 mg/kg

Fourth cohort enrollment underway

正在进行第四次队列登记

Company to hold conference call at 8:30am ET today

公司将于美国东部时间今天上午8:30召开电话会议

SAN DIEGO, June 24, 2024 /PRNewswire/ -- Regulus Therapeutics, Inc. (Nasdaq: 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 the third cohort of patients in its Phase 1b MAD study of RGLS8429 for the treatment of ADPKD..

圣地亚哥，2024年6月24日/PRNewswire/--Regulus Therapeutics，Inc.（纳斯达克：RGLS），一家专注于发现和开发靶向microRNA的创新药物（“公司”或“Regulus”）的生物制药公司，今天宣布了第三组患者在其用于治疗ADPKD的RGLS8429 1b期MAD研究中的积极结果。。

The Phase 1b MAD study is a double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of RGLS8429 in adult patients with ADPKD. The study is evaluating RGLS8429 treatment across three different weight-based dose levels and one fixed dose level, including measuring changes in urinary polycystins 1 and 2 (PC1 and PC2), htTKV, cyst architecture, and overall kidney function.

。该研究正在评估三种不同的基于体重的剂量水平和一种固定剂量水平的RGLS8429治疗，包括测量尿多囊蛋白1和2（PC1和PC2），htTKV，囊肿结构和整体肾功能的变化。

PC1 and PC2 are the protein products of the PKD1 and PKD2 genes and have been shown to inversely correlate with disease severity. Enrollment in the fourth cohort, which will include up to 30 patients, has been initiated and patients will receive an open label fixed dose of 300 mg of RGLS8429 every other week for three months.

PC1和PC2是PKD1和PKD2基因的蛋白质产物，已显示与疾病严重程度呈负相关。已经开始招募第四个队列，其中将包括多达30名患者，患者将每隔一周接受300毫克RGLS8429的开放标签固定剂量，为期三个月。

In addition to PC1 and PC2 and safety, imaging biomarkers will also be evaluated..

除了PC1和PC2以及安全性外，还将评估成像生物标志物。。

In the third cohort, 16 subjects were randomized 3:1 to receive either 3 mg/kg of RGLS8429 or placebo every other week for three months.

在第三组中，16名受试者以3:1的比例随机分组，每隔一周接受3 mg/kg的RGLS8429或安慰剂治疗三个月。

RGLS8429 was well tolerated with no safety concerns

RGLS8429耐受性良好，无安全隐患

Continued evidence of a mechanistic dose response was observed following completion of 3 mg/kg dose level based on urinary PC1 and PC2

根据尿PC1和PC2，在完成3 mg/kg剂量水平后，观察到持续的机械剂量反应证据

3 mg/kg demonstrated more consistent increases in PC1 and PC2 across patients compared to earlier cohorts

与早期队列相比，3 mg/kg的患者PC1和PC2的增加更为一致

Percent change from baseline in PC1 and PC2 demonstrated a dose response across all doses tested, with statistical significance seen at 3 mg/kg compared to placebo

PC1和PC2与基线相比的百分比变化表明，所有测试剂量均存在剂量反应，与安慰剂相比，在3 mg/kg时具有统计学意义

Exploratory MRI imaging analysis suggested RGLS8429 reduced htTKV at 3 mg/kg after 3 months of dosing

探索性MRI成像分析表明，给药3个月后，RGLS8429将htTKV降低至3 mg/kg

70% of subjects demonstrated reductions in htTKV following completion of 3 mg/kg dose level

70%的受试者在完成3 mg/kg剂量水平后表现出htTKV降低

'We are pleased to see the consistent mechanistic response and reduction in htTKV at the 3mg/kg dose level of RGLS8429 along with an appropriate safety and tolerability profile,' said Preston Klassen, M.D., President and Head of Research & Development.  'These data support our ongoing and final 300 mg fixed dose cohort in this Phase 1b trial.

“我们很高兴看到在RGLS8429的3mg/kg剂量水平下，htTKV的持续机制反应和降低，以及适当的安全性和耐受性特征，”医学博士Preston Klassen说，他是研发部总裁。“这些数据支持我们在这项1b期试验中正在进行的和最终的300毫克固定剂量队列。

We believe the data from this study will form the basis for a potentially pivotal Phase 2/3 study of RGLS8429 under an Accelerated Approval regulatory pathway to be discussed with the FDA.'.

我们相信，这项研究的数据将为RGLS8429的潜在关键2/3期研究奠定基础，该研究将与FDA讨论加速批准监管途径。”。

'Building on the positive results from our first two cohorts, these cohort 3 data, particularly the reduction in htTKV seen in the majority of patients, further strengthen our conviction in RGLS8429's ability to potentially address the underlying, genetic cause of ADPKD,' said Jay Hagan, CEO of Regulus Therapeutics.

Regulus Therapeutics首席执行官杰伊·哈根（JayHagan）说：“基于我们前两个队列的积极结果，这些队列3数据，特别是大多数患者的htTKV降低，进一步增强了我们对RGLS8429潜在解决ADPKD潜在遗传原因的能力的信心。”。

'We anticipate requesting an End-of-Phase 1 meeting with the FDA in the fourth quarter of this year and look forward to providing a data update from the open-label fourth and final cohort of the Phase 1b MAD study by year-end.'.

“我们预计将于今年第四季度结束与FDA的第一阶段会议，并期待在年底前提供1b期MAD研究开放标签第四也是最后一组的数据更新。”。

More information about the MAD clinical trial is available at clinicaltrials.gov (NCT05521191).

有关MAD临床试验的更多信息，请访问clinicaltrials.gov（NCT05521191）。

Conference Call Information

电话会议信息

The Company will host a conference call and live audio webcast on June 24, 2024, at 8:30am Eastern Time. To access the call, please dial 1-833-816-1394 (domestic) or 1-412-317-0487 (international). The live webcast can be found under 'Events and Presentations' through the investor relations section of the Company's website.

该公司将于2024年6月24日东部时间上午8:30举行电话会议和现场音频网络广播。要拨打电话，请拨打1-833-816-1394（国内）或1-412-317-0487（国际）。现场直播可通过公司网站的投资者关系部分在“活动和演示”下找到。

To access the telephone replay of the call, dial 1-877-344-7529 (domestic) or 1-412-317-0088 (international), passcode ID 6325389. The webcast and telephone replay will be archived on the Company's website at www.regulusrx.com following the call..

要访问电话重播，请拨打1-877-344-7529（国内）或1-412-317-0088（国际），密码ID 6325389。通话结束后，网络广播和电话回放将存档在公司网站www.regulusrx.com上。。

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.

由PKD1或PKD2基因突变引起的常染色体显性多囊肾病（ADPKD）是最常见的人类单基因疾病之一，也是终末期肾病的主要原因。该疾病的特征是主要在肾脏中形成多个充满液体的囊肿，在肝脏和其他器官中的程度较小。

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

肾囊肿细胞过度增殖是一个重要的病理特征，最终导致60岁左右的ADPKD患者中约50%的终末期肾病。仅在美国就有大约160000人被诊断出患有这种疾病，估计全球患病率为400万至700万。。

About RGLS8429

关于RGLS8429

RGLS8429 is a novel, next generation oligonucleotide for the treatment of ADPKD designed to inhibit miR-17 and to preferentially target the kidney. Administration of RGLS8429 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 September 2022.

RGLS8429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，RGLS8429的给药显示出肾功能，大小和其他疾病严重程度指标的明显改善。。

The Phase 1 SAD study demonstrated that RGLS8429 has a favorable safety and PK profile. RGLS8429 was well-tolerated with no serious adverse events reported and plasma exposure was approximately linear across the four doses tested. In the Phase 1b MAD study Regulus announced topline data from the first cohort of patients in September 2023, from the second cohort of patients in March 2024 and from the third cohort of patients in June 2024.

第一阶段SAD研究表明，RGLS8429具有良好的安全性和PK特征。RGLS8429耐受性良好，无严重不良事件报告，血浆暴露在四个剂量测试中大致呈线性。在1b期MAD研究中，Regulus宣布了2023年9月第一组患者、2024年3月第二组患者和2024年6月第三组患者的topline数据。

Regulus initiated enrollment in the fourth cohort of patients in May 2024. Patients in the fourth cohort will receive an open label, 300 mg fixed dose of RGLS8429 administered every other week for three months..

Regulus于2024年5月开始招募第四批患者。第四组患者将每隔一周服用300 mg固定剂量的开放标签RGLS8429，持续三个月。。

About Regulus

关于Regulus

Regulus Therapeutics Inc. (Nasdaq: 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 Therapeutics Inc.（纳斯达克：RGLS）是一家生物制药公司，专注于发现和开发针对microRNA的创新药物。Regulus利用其寡核苷酸药物发现和开发专业知识开发了一条管道，并在microRNA领域拥有丰富的知识产权。

Regulus maintains its corporate headquarters in San Diego, CA..

Regulus的公司总部位于加利福尼亚州圣地亚哥。。

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 RGLS8429 program and preclinical pipeline, the potential that RGLS8429 may be eligible for an Accelerated Approval pathway, the expected timing for reporting topline data, and the timing and future occurrence of other preclinical and clinical activities.

本新闻稿中关于非历史事实的声明是1995年《私人证券诉讼改革法案》所指的“前瞻性声明”，包括与公司RGLS8429计划和临床前管道相关的声明，RGLS8429可能有资格获得加速批准途径的可能性，报告topline数据的预期时间，以及其他临床前和临床活动的时间和未来发生。

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 'believes,' 'anticipates,' 'plans,' 'expects,' 'intends,' 'will,' 'goal,' 'potential' and similar expressions are intended to identify forward-looking statements.

由于此类声明存在风险和不确定性，实际结果可能与此类前瞻性声明明示或暗示的结果存在重大差异。诸如“相信”、“预期”、“计划”、“期望”、“打算”、“意志”、“目标”、“潜力”等词语以及类似的表达方式旨在识别前瞻性陈述。

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, that 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 review of the data related to the clinical trial and may not be indicative of future results, the FDA has not designated RGLS8429 for an Accelerated Approval pathway and such designation may not lead to a faster development, regulatory review or approval process and does not increase the likeliho.

这些前瞻性陈述基于Regulus目前的预期，并涉及可能永远不会实现或可能被证明不正确的假设。由于各种风险和不确定性，实际结果和事件发生的时间可能与这些前瞻性声明中预期的结果有很大不同，这些风险和不确定性包括但不限于我们发现和开发药物的方法是新颖的，可能永远不会产生适销对路的产品，初步或一线结果是基于对关键疗效和安全性数据的初步分析，这些数据可能会在对与临床试验相关的数据进行更全面的审查后发生变化，并且可能不会指示未来的结果，FDA尚未指定RGLS8429用于加速批准途径，这种指定可能不会导致更快的开发，监管审查或批准过程，也不会增加可能性。

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SOURCE Regulus Therapeutics Inc.

SOURCE Regulus Therapeutics Inc。

Company Codes: NASDAQ-NMS:RGLS

公司代码：NASDAQ-NMS：RGLS