重磅！复宏汉霖新冠病毒中和抗体HLX70新药临床试验申请获美国FDA批准
2020年10月4日，复宏汉霖（香港联交所代码：2696）宣布新冠病毒中和抗体HLX70针对新冠病毒肺炎（COVID-19）、新冠病毒引起的急性呼吸窘迫综合征（ARDS）或多重器官衰竭（multiple organ failure）等适应症的新药临床试验申请（Investigational New Drug Application, IND）获美国食品药品监督管理局（United States Food and Drug Administration, US FDA）批准。复宏汉霖也由此成为首个自主向美国FDA递交新冠病毒中和抗体临床试验申请并获得批准的中国制药企业。
候选抗体HLX70为利用基因工程技术构建的靶向新冠病毒SARS-CoV-2表面刺突蛋白（S蛋白）S1亚基上受体结合域（receptor binding domain, RBD）的全人源单克隆抗体，是典型的IgG1 Kappa免疫球蛋白。新冠病毒感染人体细胞的关键步骤之一为病毒表面S蛋白S1亚基的RBD区域与人体细胞表面的血管紧张素转化酶2 (angiotensin II converting enzyme 2，ACE2) 蛋白结合，从而引发人体细胞的内吞作用将病毒吞入细胞内[1,2]。HLX70与病毒S蛋白的结合位点亦为S蛋白RBD区域，且HLX70与S蛋白RBD区域的亲和力更高。当HLX70结合到病毒表面的S蛋白RBD区域后，病毒将无法与人体细胞表面的ACE2结合，从而达到抑制病毒感染的效果。
2020年5月，面对新冠疫情的全球蔓延，复宏汉霖与三优生物、之江生物达成合作协议，共同研发针对COVID-19的全人源抗体药物。基于公司丰富的抗体研发经验以及完善的抗体研发、生产与商业化全产业链平台，复宏汉霖在候选抗体后续开发与生产中承担主导任务。遵从人用药物注册技术要求国际协调会议（ICH）的指导原则，复宏汉霖对HLX70进行了药理学、药代动力学和毒理学等临床前研究，以评估HLX70的有效性和安全性。体外药效结果表明，HLX70与新冠病毒S蛋白RBD区域具有较强的特异性结合能力，能够在蛋白和细胞水平显著阻断新冠病毒S蛋白RBD与人ACE2的结合，并能阻止不同新冠病毒毒株感染非洲绿猴肾细胞。体内药效结果表明，HLX70在人ACE2转基因小鼠模型中对新冠病毒感染具有明确的保护效果。体内重复给药毒性试验显示，静脉注射HLX70具有良好的安全性。
除HLX70外，公司自主开发的另一款ACE2-Fc受体融合蛋白HLX71也在加速推进临床前研究，两个相关研发项目目前均已获得国家重点研发计划“公共安全风险防控与应急技术装备”重点专项立项支持。同时，复宏汉霖亦就HLX71及HLX70/HLX71联合用药方案递交了中国发明专利申请。此次复宏汉霖成为首个自主向美国FDA递交新冠病毒中和抗体临床试验申请并获得批准的中国制药企业，也显示了公司多方面寻求加快研发进展，积极承担企业社会责任的速度与决心。未来，复宏汉霖将携手项目合作伙伴加快开发中和作用强、体内外模型评价充分、产业化成功率高的抗新冠病毒中和抗体，并不断探索于全球更多国家开展国际临床研究的可能，为抗疫贡献更多力量。
关于复宏汉霖
复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供质高价优的创新生物药，产品覆盖肿瘤、自身免疫疾病等领域。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司在中国上海、中国台北和美国加州均设有研发中心，按照国际GMP标准进行生产和质量管控，位于上海徐汇的生产基地已获得中国和欧盟GMP认证。
复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖20多种创新单克隆抗体，并全面推进基于自有抗PD-1单抗HLX10的肿瘤免疫联合疗法。截至目前，公司已成功上市国内首个生物类似药汉利康Ⓡ（利妥昔单抗），首个中欧双批的国产生物类似药汉曲优Ⓡ（曲妥珠单抗，欧盟商品名：Zercepac），HLX03阿达木单抗与HLX04贝伐珠单抗上市注册申请正在审评中，其中HLX03已获得优先审评审批资格，有望于今年上市。复宏汉霖同步就10个产品、8个联合治疗方案于全球范围内开展20多项临床试验，产品对外授权覆盖全球近100个国家和地区。
Investigational New Drug Application of Henlius SARS-CoV-2 Neutralizing Antibody HLX70 Approved by US FDA
Shanghai, China, Oct, 4th, 2020 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the Investigational New Drug (IND) application of the SARS-CoV-2 neutralizing antibody HLX70 for the treatment of COVID-19 and acute respiratory distress syndrome (ARDS) or multiple organ failure caused by COVID-19 has been approved by the U.S. Food and Drug Administration (FDA). With this IND application, Henlius becomes the first Chinese biopharmaceutical company that has independently filed an IND application for a SARS-CoV-2 neutralizing antibody to the U.S. FDA and has received the approval.
HLX70 is a genetically engineered fully humanized monoclonal antibody that targets the receptor-binding domain (RBD) of the S1 subunit of SARS-CoV-2 spike protein (S protein) and is a typical IgG1 Kappa immunoglobulin. Binding of virus RBD domain with human angiotensin II converting enzyme 2 (hACE2) will lead to cell endocytosis of the virus, which is a critical step for viral entry [1,2]. HLX70 can competitively bind with the viral RBD domain with higher affinity and thus block the binding between viral RBD and hACE2 protein, therefore protecting the cells from virus infection.
With the spread of the pandemic of COVID-19, Henlius has reached a collaboration with Sanyou Biopharmaceuticals and Shanghai ZJ Bio-Tech to co-develop fully humanized antibody candidates for the treatment of COVID-19 in May 2020. Based on the company's entensive experience in R&D of innovative antibodies and its integrated platform of R&D, manufacturing and commercialisation, Henlius has taken a leading role in the development and manufacturing of the candidate antibody. Nonclinical pharmacology, pharmacokinetics and toxicology studies were performed by Henlius to evaluate the efficacy and safety of HLX70 according to The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. The in vitro studies showed that HLX70 has a strong specific binding affinity to RBD of the S1 subunit of SARS-CoV-2 and can significantly block the binding of SARS-CoV-2 S1 with the hACE2 at both protein and cell levels. HLX70 also exhibited high neutralizing activity against different strains of SARS-CoV-2 virus on Vero cells. The in vivo study in hACE2 transgenic mice model demonstrated that HLX70 is a potent neutralizing antibody, which is effective in protection of hACE2 transgenic mice against SARS-CoV-2. Repeated dose toxicity study in vivo demonstrated that HLX70 is well tolerated following intravenous injection.
In addition to HLX70, Henlius is also accelerating the preclinical study of another independently developed ACE2-Fc receptor fusion protein HLX71 for the treatment of COVID-19. As of now, two relevant projects of HLX70 and HLX71 have already received support from the National Major Research and Development Plan of "Public Safety Risk Prevention and Control and Emergency Technical Equipment". Meanwhile, Henlius has also submitted relevant patent applications for HLX71 and HLX70/HLX71 combination therapy in China. As the first Chinese biopharmaceutical company that independently filed an IND application for a SARS-CoV-2 neutralizing antibody to the U.S. FDA and has received the approval, Henlius highlights the company’s speed and determination in the research and development of antibody and fusion protein against COVID-19, and actively takes on corporate social responsibilities. In the future, Henlius will collaborate with partners to further speed up the development of SARS-CoV-2 neutralizing antibody to make sure that the antibody has strong neutralization effect, is fully evaluated in vivo and in vitro and can be manufactured in large scale. Henlius will also continue to explore the possibility of global clinical research in more countries around the world to contribute more in the fight against COVID-19.
About Henlius
Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology and autoimmune diseases. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialisation. It has three R&D facilities in Shanghai, Taipei and California and a Shanghai-based manufacturing facility certificated by China and the European Union (EU) Good Manufacturing Practice (GMP).
Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monoclonal antibodies (mAb) and has continued to explore immuno-oncology combination therapies with proprietary HLX10 (anti-PD-1 mAb) as backbone. Up to date, Henlius has launched two products, 汉利康® (HLX01, rituximab injection) , the first biosimilar approved in China and 汉曲优® (HLX02, trastuzumab injection, Zercepac® in the EU), the first Chinese mAb biosimilar launched in both China and Europe. 汉曲优® will bring more treatment options to patients with HER2 positive breast and gastric cancer worldwide. Two products (HLX03, adalimumab injection and HLX04, bevacizumab injection) were accepted for New Drug Application (NDA) review by the NMPA with HLX03 to be potentially launched within 2020. What’s more, Henlius has conducted over 20 clinical studies for 10 products and 8 combination therapies worldwide. Products have been licensed out to nearly 100 countries and regions.
参考文献
1.Gallagher T M, Buchmeier M J. Coronavirus spike proteins in viral entry and pathogenesis[J]. Virology, 2001, 279(2): 371-374.
2.Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2[J]. Science, 2020, 367(6485): 1444-1448.
联系方式
媒体：PR@Henlius.com
投资者：IR@Henlius.com
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