Ascletis宣布皮下注射的PD-L1抗体ASC22（Envafolimab）的IIa期HBV阳性

StephenW

Ascletis Announces Positive Phase IIa HBV Results on Subcutaneously Administered PD-L1 Antibody ASC22 (Envafolimab)

-One patient achieved Hepatitis B surface antigen (HBsAg) reduction of 1.2 log10 IU/mL in the 2.5 mg/kg single dose cohort (n=3)

-Trend of dose dependent HBsAg reduction observed

News provided by
Ascletis Pharma Inc.

May 04, 2021, 20:30 ET
Share this article

HANGZHOU and SHAOXING, China, May 4, 2021 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX:1672) today announces the positive Phase IIa clinical results of ASC22 (Envafolimab), which is a first-in-class, subcutaneously administered PD-L1 antibody for chronic hepatitis B (CHB) functional cure.

ASC22 Phase IIa clinical trial is a single dose escalation study of three subcutaneously administered doses (0.3, 1.0 and 2.5 mg/kg, three patients per dose) with 12-week follow-up to explore the safety and preliminary efficacy of ASC22 in CHB patients (ClinicalTrials.gov Identifier: NCT04465890). The primary efficacy endpoint is HBsAg reduction during 12-week follow-up after the single dose administration. Median baseline HBsAg of nine CHB patients enrolled was 3.0 log10 IU/mL.

The phase IIa data indicated that there is a trend of dose dependent HBsAg reduction after single dose administration of 0.3, 1.0 or 2.5 mg/kg ASC22. Eight out of nine patients treated with ASC22 exhibited some decline in HBsAg at the end of 12-week follow-up. Among three patients receiving 2.5 mg/kg dose, one patient achieved a maximum HBsAg reduction of 1.2 log10 IU/mL during the 12-week follow-up.

ASC22 is safe and well tolerated at all three dose levels with only grade 1 adverse effects. There were no grade 2 or above adverse effects observed during 12-week follow-up. Single dose administrations up to 2.5 mg/kg ASC22 did not affect alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (all below upper limit of norm) during 12-week follow-up.

On January 12, 2019, Ascletis entered an exclusive licensing agreement for PD-L1 antibody ASC22 (KN035) with Suzhou Alphamab Co., Ltd. (Alphamab). Under the terms of the agreement, Ascletis has an exclusive license from Alphamab to develop and commercialize ASC22 (KN035) for all viral diseases including Hepatitis B and HIV in Greater China. For ASC22 (KN035) in viral indications worldwide outside Greater China, Ascletis will be eligible to share certain economics such as upfront, milestone payments and royalties, depending on the development and regulatory status of ASC22 (KN035) inside Greater China.

"I am excited by > 1.0 log HBsAg reduction with only single dose ASC22," said Guiqiang Wang, MD, Principal Investigator of the Study, Vice-President of Chinese Society of Physicians for Infectious Diseases and Director of Centre for Liver Diseases at Peking University First Hospital, "As an immunotherapy, ASC22 has the potential to functionally cure CHB and offers convenient subcutaneous injections for patients. I am looking forward to the data from ASC22 Phase IIb HBV trial with much larger sample sizes."

"We are thrilled by positive Phase IIa data and believe this first-in-class immunotherapy has great potential to functionally cure CHB." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

The single dose results are really intriguing. With its advantage in safety, convenience, and compliance, KN035 (ASC22) is potentially bring solution for chronical virus diseases, including HBV and HIV." said Dr. Ting Xu, Chairman of Alphamab.

About ASC22

ASC22, also known as KN035 or Envafolimab, licensed exclusively by Ascletis for all viral indications from Alphamab, is a PD-L1 single domain antibody Fc fusion and has the advantages of subcutaneous injection and good stability at room temperature. These would be of great value to improve patients' compliance and quality of life and to help realize the goal of long-term management of chronic diseases such as chronic hepatitis B. Ascletis and Suzhou Alphamab Co., Ltd. announced on January 14, 2019 the strategic collaboration and licensing agreement for anti-PD-L1 to treat Hepatitis B and other viral diseases. Envafolimab has been enrolled in more than 1,000 patients and has shown good safety and efficacy in multiple tumor indications. Alphamab and its partner have submitted a biologic license application (BLA) for MSI-H solid tumors.

StephenW

Ascletis宣布皮下注射的PD-L1抗体ASC22（Envafolimab）的IIa期HBV阳性结果

-在2.5 mg / kg单剂量组中，一名患者的乙型肝炎表面抗原（HBsAg）降低了1.2 log10 IU / mL（n = 3）

-观察到剂量依赖性HBsAg降低的趋势

新闻提供者
Ascletis Pharma Inc.

美国东部时间2021年5月4日，20：30
分享这篇文章

美通社-PR Newswire / 2021年5月4日，中国杭州和绍兴— Ascletis Pharma Inc.（HKEX：1672）今天宣布ASC22（Envafolimab）IIa期临床阳性结果，这是首例皮下给药的PD -L1抗体可用于慢性乙型肝炎（CHB）功能治愈。

ASC22 IIa期临床试验是对三种皮下给药剂量（0.3、1.0和2.5 mg / kg，每剂三位患者）进行单次剂量递增研究，并进行了为期12周的随访，以探讨ASC22在CHB患者中的安全性和初步疗效（ClinicalTrials.gov标识符：NCT04465890）。主要功效终点是单剂给药后12周随访期间HBsAg降低。 9名CHB患者的基线HBsAg中位数为3.0 log10 IU / mL。

IIa期数据表明，单剂量给药0.3、1.0或2.5 mg / kg ASC22后，存在剂量依赖性HBsAg降低的趋势。在12周的随访结束时，接受ASC22治疗的9名患者中有8名表现出HBsAg有所下降。在接受2.5 mg / kg剂量的三名患者中，一名患者在12周的随访中最大HBsAg降低量为1.2 log10 IU / mL。

ASC22在所有三个剂量水平上都是安全且耐受性良好的，仅具有1级不良反应。在12周的随访中未观察到2级或以上的不良反应。在12周的随访中，单剂量最高2.5 mg / kg ASC22的给药不会影响丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的水平（均低于标准上限）。

在2019年1月12日，Ascletis与苏州阿尔法单克隆抗体有限公司（Alphamab）签订了PD-L1抗体ASC22（KN035）的独家许可协议。根据该协议的条款，Ascletis拥有Alphamab的独家许可，可以开发和商业化针对大中华区所有乙型肝炎和艾滋病毒的病毒性疾病的ASC22（KN035）。对于大中华地区以外的全球病毒适应症中的ASC22（KN035），Ascletis将有资格分享某些经济学信息，例如预付款，里程碑付款和特许权使用费，具体取决于大中华地区ASC22（KN035）的发展和监管状况。

研究首席研究员，中国传染病医师学会副会长，北京大学肝病研究中心主任王桂强说：“仅用单剂量的ASC22，HBsAg降低> 1.0 log HBsAg，我就感到很兴奋。”第一医院，“作为一种免疫疗法，ASC22具有在功能上治愈CHB的潜力，并为患者提供了方便的皮下注射。我期待ASC22 IIb HBV阶段的临床试验获得更大的样本量。

“我们对IIa期阳性数据感到兴奋，并相信这种一流的免疫疗法在功能上治愈CHB方面具有巨大潜力。” Ascletis的创始人，董事长兼首席执行官Wu Jinzi J. Wu表示。

单剂量的结果确实很有趣。 KN035（ASC22）凭借其在安全性，便利性和合规性方面的优势，有望为包括HBV和HIV在内的慢性病毒疾病带来解决方案。” Alphamab董事长许挺博士说。

关于ASC22

ASC22，也称为KN035或Envafolimab，由Alclemab独家授权用于Alphamab的所有病毒适应症，是PD-L1单域抗体Fc融合体，具有皮下注射的优势，并且在室温下具有良好的稳定性。这些对于提高患者的依从性和生活质量以及帮助实现对慢性疾病如慢性乙型肝炎的长期管理具有重要价值.Ascletis和苏州阿尔法单克隆抗体有限公司于2019年1月14日宣布抗PD-L1治疗乙型肝炎和其他病毒性疾病的战略合作和许可协议。 Envafolimab已被纳入1000多例患者，并在多种肿瘤适应症中显示出良好的安全性和有效性。 Alphamab及其合作伙伴已提交了针对MSI-H实体瘤的生物许可申请（BLA）。

乙肝人1949

好消息

pppq123

感觉还是不行，只是下降，具体下降多少呢？有点看不懂

windu

不错，非常好，之前美国有一篇文章，用pd-1抗体做实验，一个月就干掉了表面抗原并出现抗体，好像是一个月两针，现在歌礼的人体临床似乎也有类似的效果

乙肝人1949

至少是黑夜里里，远处的一点火星

StephenW

回复 pppq123 的帖子

1.0 log 10 減少 = 90% 減少
例如 :
1000 --> 1000 - 90/100 x 1000 = 1000 - 900 = 100
100   --> 100 - 90/100 x 100 = 100 - 90 = 10

2.0 log 10 減少 = 99% 減少

1000 --> 10
100 --> 1