歌礼宣布美国Ib期多剂量递增研究的小分子口服GLP-1R激动剂ASC30取得积极的初步结果，并向FDA提交13周IIa期研究方案-动脉网

Ascletis Announces Positive Topline Results of U.S. Phase Ib Multiple Ascending Dose Study of Small Molecule Oral GLP-1R Agonist ASC30 and Submission of 13-week Phase IIa Study Protocol to FDA

CISION 等信源发布 2025-04-23 07:30

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可切换为仅中文

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ASC30 oral once-daily tablet demonstrated a 6.5% placebo-adjusted

ASC30 口服每日一次片剂显示出 6.5% 的安慰剂调整后效果

mean

平均数

body weight reduction from baseline after four-week treatment using weekly doses with titrations of 2 mg, 10 mg, 20 mg

四周治疗后，使用每周剂量递增2毫克、10毫克、20毫克的体重较基线减少情况

，

and 40 mg doses.

和40毫克剂量。

ASC30

oral

口服的

once-daily

每日一次

tablet

平板电脑

also demonstrated a 4.5% placebo-adjusted mean body weight reduction from baseline after four-week treatment using weekly doses with titrations of 2 mg, 5 mg, 10 mg, and 20 mg doses. No vomiting was seen in this dose group.

还展示了在使用每周剂量进行四周治疗后，相对于安慰剂组平均体重从基线减少了4.5%，剂量逐步增加分别为2毫克、5毫克、10毫克和20毫克。在此剂量组中未出现呕吐现象。

Data from three different weekly titration schemes in the Phase Ib trial support utilizing a 'lower starting dose and slower titration

第一b阶段试验中三种不同的每周滴定方案的数据支持使用“较低的起始剂量和较慢的滴定”

strategy for a 13-week Phase IIa study design of ASC30 oral once-daily tablet.

13周二期a阶段研究设计的ASC30口服每日一次片剂策略。

HONG KONG

香港特别行政区

April 22, 2025

2025年4月22日

/PRNewswire/ -- Ascletis Pharma Inc. (HKEX:1672, 'Ascletis') announces today positive topline results of its randomized, double-blind, placebo-controlled Phase Ib multiple ascending dose (MAD) study (

/PRNewswire/ -- 歌礼制药有限公司（HKEX:1672，'歌礼'）今天宣布了其随机、双盲、安慰剂对照的Ib期多剂量递增（MAD）研究的积极顶线结果 (

NCT06680440

), conducted in the U.S., of ASC30 oral once-daily tablet in participants with obesity (body mass index (BMI): 30-40 kg/m

在美国进行的ASC30口服每日一次片剂针对肥胖（体重指数（BMI）：30-40 kg/m²）参与者的试验

). The Phase Ib MAD study consisted of three cohorts, each with a different weekly titration scheme, for a total of four-week treatment and one-week follow up. Scheme 1 (mid starting dose, slow titration: 2 mg, 5 mg, 10 mg, and 20 mg); Scheme 2 (mid starting dose, normal titration: 2 mg, 10 mg, 20 mg, and 40 mg); and Scheme 3 (high starting dose, fast titration: 5 mg, 15 mg, 30 mg, and 60 mg).

）。第Ib阶段的多剂量递增研究（MAD）包括三个队列，每个队列采用不同的每周剂量递增方案，总共进行四周治疗和一周随访。方案1（中等起始剂量，缓慢递增：2毫克、5毫克、10毫克和20毫克）；方案2（中等起始剂量，正常递增：2毫克、10毫克、20毫克和40毫克）；方案3（高起始剂量，快速递增：5毫克、15毫克、30毫克和60毫克）。

Based on single ascending dose (SAD) data in participants with obesity, Schemes 1 and 2 were designed to investigate tolerability and efficacy. All participants with obesity stayed at the clinical site from day 1 to day 2 and from day 27 to day 29. For other days during the study, participants maintained their habitual eating and physical activity patterns as out-patients..

基于肥胖参与者中的单次递增剂量（SAD）数据，设计了方案1和方案2以研究耐受性和有效性。所有肥胖参与者在第1天到第2天以及第27天到第29天期间留在临床试验地点。在研究的其他日子里，参与者作为门诊患者维持其日常饮食和体力活动模式。

Mean body weight reductions from baseline for Scheme 1 (mid starting dose, slow titration: 2 mg, 5 mg, 10 mg, and 20 mg) and Scheme 2 (mid starting dose, normal titration: 2 mg, 10 mg, 20 mg, and 40 mg) were 4.3% (n=7,

方案1（中等起始剂量，缓慢滴定：2 mg、5 mg、10 mg 和 20 mg）和方案2（中等起始剂量，正常滴定：2 mg、10 mg、20 mg 和 40 mg）的基线体重平均减少率为4.3%（n=7，

=0.0002 vs placebo) and 6.3% (n=8,

=0.0002 vs 安慰剂）和 6.3%（n=8，

<0.0001 vs placebo), respectively, after four-week treatment. No weight plateau was observed. Mean body weight increase from baseline for placebo was 0.2% (n=6, two placebos from each of three schemes). Placebo adjusted mean body weight reductions for Schemes 1 and 2 from baseline were 4.5% and 6.5%, respectively.

四周治疗后，与安慰剂相比，差异分别为<0.0001。未观察到体重平台期。安慰剂组自基线的平均体重增加为0.2%（n=6，三个方案中每个方案各两个安慰剂）。方案1和方案2相对于安慰剂的自基线平均体重减少分别为4.5%和6.5%。

The maximum body weight reductions from baseline were 7.6% and 9.1% for Schemes 1 and 2, respectively. ASC30 oral once-daily tablet was generally safe and well tolerated among Schemes 1 and 2, with a favorable safety profile. The majority of gastrointestinal (GI)-related adverse events (AEs) were mild (Grade 1) and short-lived.

方案1和方案2的体重较基线的最大降幅分别为7.6%和9.1%。ASC30口服每日一次片剂在方案1和方案2中通常安全且耐受性良好，具有良好的安全性特征。大多数胃肠道（GI）相关不良事件（AEs）为轻度（1级）且短暂。

Schemes 1 and 2 demonstrated improved or comparable GI tolerability to the .

方案1和方案2显示出与之相当或改善的胃肠耐受性。

GLP-1

class such as orforglipron. For example, Scheme 1 had no incidences of vomiting.

诸如orforglipron类。例如，方案1没有出现呕吐的情况。

After reviewing the safety and efficacy results of the first two dosing schemes, a third dosing scheme (high starting dose, fast titration: 5 mg, 15 mg, 30 mg, and 60 mg) was designed to help validate the optimal combination of tolerability and efficacy seen in Schemes 1 and 2. Mean body weight reduction from baseline for Scheme 3 was 4.8% (n=7, .

在审查了前两种剂量方案的安全性和有效性结果后，设计了第三种剂量方案（高起始剂量，快速滴定：5 毫克、15 毫克、30 毫克和 60 毫克），以帮助验证方案 1 和方案 2 中观察到的最佳耐受性和有效性组合。方案 3 的平均体重较基线减少为 4.8%（n=7，。

=0.0015 vs placebo) after four-week treatment. Placebo-adjusted mean body weight reduction from baseline was 5.0%. The maximum body weight reduction from baseline was 9.3%. In Scheme 3, there were two outliers, each with body weight reduction of 1.8% from baseline, which were not seen in Schemes 1 or 2. Excluding these two outliers, placebo-adjusted mean body weight reduction from baseline in Scheme 3 was 6.1%, comparable to Scheme 2.

与安慰剂相比（=0.0015），四周治疗后，体重较基线平均减少5.0%。体重较基线最大减少为9.3%。在方案3中，出现了两个异常值，每个异常值显示体重较基线减少了1.8%，而这些在方案1或2中未出现。排除这两个异常值后，方案3中体重较基线的安慰剂调整平均减少为6.1%，与方案2相当。

The maximum body weight reduction from baseline of Scheme 3 was also comparable to Scheme 2 (9.3% and 9.1%, respectively). Moreover, the GI tolerability observed in Scheme 3 was less than that of Schemes 1 and 2, due to its high starting dose, fast titration design..

方案3的最大体重减轻幅度与方案2相当（分别为9.3%和9.1%）。此外，由于方案3的起始剂量较高且滴定设计较快，其胃肠道耐受性较方案1和方案2差。

For all the above mentioned three schemes, no serious adverse events (SAEs) were reported. There were no Grade 3 or higher AEs including GI-related AEs observed. There were no elevations of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBL) during the treatment.

对于上述三种方案，均未报告严重不良事件（SAEs）。未观察到包括胃肠道相关不良事件在内的3级或更高级别的不良事件（AEs）。治疗期间未发现肝酶升高，包括丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆红素（TBL）。

There were no abnormal findings in laboratory tests, vital signs, ECGs (electrocardiograms, including QTc intervals), and physical exams..

实验室检查、生命体征、心电图（包括QTc间期）和体格检查均无异常发现。

Both tolerability and efficacy data from the ASC30 tablet Phase Ib study support a 'lower starting dose and slower titration' strategy for a 13-week Phase IIa study design of ASC30 oral once-daily tablet. The 13-week Phase IIa study protocol, which has a low starting dose and slow weekly titration to the desired maintenance doses, has been submitted to the U.S.

ASC30片剂Ib期研究的耐受性和疗效数据均支持在ASC30口服每日一次片剂的13周IIa期研究设计中采用“较低起始剂量和更慢滴定”的策略。该13周IIa期研究方案起始剂量低，并以缓慢的每周滴定方式达到目标维持剂量，已提交至美国。

Food and Drug Administration (FDA) following a preliminary consultation with FDA. The Company expects to initiate the 13-week Phase IIa study in the U.S. at the beginning of the third quarter of 2025..

在与FDA初步协商后，FDA同意了该请求。公司预计将在2025年第三季度初在美国启动为期13周的IIa期研究。

ASC30 was discovered and developed in-house at Ascletis as a first and only investigational small molecule

ASC30是歌礼药业自主研发的首个也是唯一一个在研小分子药物

GLP-1

receptor (GLP-1R) biased agonist designed to be dosed once daily orally and once monthly subcutaneously for the treatment of obesity.

GLP-1R偏向激动剂，设计为每日一次口服和每月一次皮下注射，用于治疗肥胖症。

'We are excited that these topline results from our Phase Ib study demonstrated potential best-in-class characteristics to treat obesity,' said

“我们很高兴 Ib 期研究的这些初步结果展示了治疗肥胖症的潜在最佳特性，”表示

Jinzi Jason Wu

金子杰森·吴

, Ph.D., Founder, Chairman and CEO of Ascletis. 'Results from the Phase Ib study in U.S. informed and provided critical knowledge for our 13-week Phase IIa study design of ASC30 oral once-daily tablet. As a small molecule, ASC30 has the potential to offer both once-daily oral and once-monthly subcutaneous injection dosing options for obesity treatment, if approved.'.

博士，Ascletis创始人、董事长兼首席执行官。“美国Ib期研究的结果为我们13周的IIa期ASC30每日一次口服片剂的研究设计提供了重要信息和关键知识。作为一种小分子药物，如果获得批准，ASC30有潜力为肥胖症治疗提供每日一次口服和每月一次皮下注射的剂量选择。”

About ASC30

关于ASC30

ASC30 is an investigational GLP-1R biased small molecule agonist and has unique and differentiated properties that enable the same small molecule for both oral tablet and subcutaneous injection administrations. ASC30 is a new chemical entity (NCE), with U.S. and global compound patent protection until 2044. .

ASC30是一种在研的GLP-1R偏向性小分子激动剂，具有独特且差异化的特点，可使同一小分子适用于口服片剂和皮下注射两种给药方式。ASC30是一种新化学实体（NCE），在美国和全球范围内享有化合物专利保护直至2044年。

About Ascletis Pharma Inc.

关于歌礼制药有限公司

Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to GMP manufacturing. Led by a management team with deep expertise and a proven track record, Ascletis is focused on metabolic diseases by addressing unmet medical needs from a global perspective.

歌礼是一家创新研发驱动的生物科技公司，于香港证券交易所上市（1672.HK），覆盖从发现、开发到GMP生产的完整价值链。由具有深厚专业背景和成功经验的管理团队领导，歌礼专注于代谢性疾病，从全球视角出发满足未被满足的医疗需求。

Ascletis has multiple clinical stage drug candidates in its metabolic disease pipeline..

歌礼在代谢疾病领域拥有多个临床阶段的候选药物。

For more information, please visit

欲了解更多信息，请访问

www.ascletis.com

。

Contact:

联系：

Peter Vozzo

彼得·沃佐

ICR Healthcare