国内首款！复宏汉霖创新抗GARP单抗HLX60获NMPA临床批准
内容来源于：复宏汉霖
2022年10月17日，复宏汉霖（2696.HK）宣布，公司自主开发的HLX60（创新型抗GARP单抗）用于治疗实体瘤和淋巴瘤的临床试验申请获国家药品监督管理局批准。HLX60是国内首个获批临床的靶向GARP的单抗产品，有望成为First-in-class抗GARP单抗。
糖蛋白A重复优势蛋白（glycoprotein-A repetitions predominant，GARP）是潜伏转化生长因子β1（LTGF-β1）的对接受体，其主要在活化的调节性T细胞（Tregs）和血小板上表达[1]，在肿瘤微环境（TME）中富集并激活转化生长因子-β（TGF-β），从而抑制抗肿瘤免疫应答，促进肿瘤细胞生长、增殖和侵袭[2-3]。TGF-β是一种多效细胞因子，在多种组织中均有表达，有TGF-β1、TGF-β2、TGF-β3三个主要亚型，其中TGF-β1在细胞增殖、发育、凋亡、纤维化、血管生成、伤口愈合、癌症免疫等生物学过程的许多方面都发挥着重要作用[4-6]。
HLX60为复宏汉霖自主研发的靶向GARP的创新型单抗，其可通过特异性结合GARP，阻断GARP介导的TGF-β1的释放，逆转TME中的免疫抑制效应，提高抗肿瘤免疫应答。此外，HLX60可以通过抗体依赖细胞介导的细胞毒作用（ADCC）清除GARP阳性肿瘤细胞和Tregs等免疫抑制性细胞，从而发挥抗肿瘤作用。临床前研究结果显示，HLX60可以抑制肿瘤生长且安全性良好。同时，该药与抗PD-1单抗H药 汉斯状®（斯鲁利单抗）联用具有协同抗肿瘤效应。值得一提的是，凭借各部门的通力合作，高效运营，HLX60项目从确定分子到拿到IND批件仅用时约16个月，项目得以快速推进到临床阶段。近期，HLX60联合H药已于澳大利亚获批开展I期临床研究，拟用于晚期或转移性实体瘤的治疗。
复宏汉霖从临床需求出发，目前已打造出多元化的创新产品管线，在PD-1/L1、LAG-3、GARP、TIGIT、BRAF等创新靶点全面布局。未来，复宏汉霖也将推动更多创新产品的临床研究，以抗体技术为核心，积极开展联合治疗方案、创新靶点双特异性抗体以及抗体偶联药物（ADC）等产品的布局，期待早日为更多患者带来可负担的高品质生物药。
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可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已在中国上市5款产品，在国际上市1款产品，13项适应症获批，7个上市注册申请获得中国药监局受理。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。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，上海徐汇基地已获得中国和欧盟GMP认证，松江基地（一）也已获得中国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H药汉斯状®的肿瘤免疫联合疗法。继国内首个生物类似药汉利康®（利妥昔单抗）、中国首个自主研发的中欧双批单抗药物汉曲优®（曲妥珠单抗，欧洲商品名：Zercepac®，澳大利亚商品名：Tuzucip®和Trastucip®）、汉达远®（阿达木单抗）和汉贝泰®（贝伐珠单抗）相继获批上市，创新产品汉斯状®（斯鲁利单抗）已获批用于治疗微卫星高度不稳定（MSI-H）实体瘤，其鳞状非小细胞肺癌、广泛期小细胞肺癌和食管鳞状细胞癌3项适应症的上市注册申请也正在审评中。公司亦同步就13个产品、11个免疫联合治疗方案在全球范围内开展20多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。
The IND Application of Henlius’ Novel Anti-GARP mAb HLX60 Approved by NMPA
Shanghai, China, Oct 17th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug (IND) application for clinical trial of HLX60 (recombinant anti-GARP humanised monoclonal antibody injection), independently developed by the company, was approved by the National Medical Products Administration (NMPA) for the treatment of solid tumours and lymphomas. HLX60 is the first IND approved anti-GARP monoclonal antibody (mAb) in China and is expected to be the first-in-class anti-GARP mAb.
The glycoprotein-A repetitions predominant (GARP) is highly expressed on the surface of activated Tregs and platelets and acts as a docking receptor by binding to latent transforming growth factor-β1 (LTGF-β1) [1]. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine expressed by the majority of cells and found in many tissues. There are three TGF-β receptor ligands: TGF-β1, TGF-β2, and TGF-β3, with TGF-β1 playing critical roles in a variety of biological processes including cell proliferation, development, apoptosis, fibrosis, angiogenesis, wound healing, cancer, and many others [2–4]. It concentrates LTGF-β1 on the cell surface and releases active TGF-β1 in the tumour microenvironment (TME), thus inhibiting anti-tumour immune response and inducing tumour cell growth, proliferation and invasion [5-6].
HLX60 is a self-developed novel anti-GARP mAb that binds to GARP and specifically blocks the release of GARP mediated TGF-β1, thus relieving the immunosuppression caused by TGF-β1, reversing the immunosuppressive TME, and improving anti-tumour immune response. Furthermore, by inducing antibody dependent cell-mediated cytotoxicity (ADCC) effect, HLX60 can deplete GARP positive tumour cells as well as immunosuppressive cells such as Tregs. Several pre-clinical studies have shown that HLX60 has anti-tumour effects and has a good safety profile. Plus, HLX60 in combination with HANSIZHUANG (serplulimab), an innovative anti-PD-1 mAb independently developed by Henlius, demonstrating a synergistic effect in inhibiting tumour growth. It is worth mentioning that it only takes Henlius about 16 months to move HLX60 from molecular determination to clinical stage with a robust cross-functional coorperation. Recently, the phase 1 clinical trial application of HLX60 in combination with HANSIZHUANG for the treatment of advanced or metastatic solid tumours has been approved in Australia.
Underpinned by the patient-centric strategy, Henlius has built an innovative product pipeline with many emerging targets, including PD-1/L1, LAG-3, GARP, TIGIT, BRAF etc. Regarding antibody technology as a core, Henlius will continue conducting clinical studies for more innovative products in bispecific antibodies and the antibody-drug conjugates (ADC) and exploring combination therapies with improved efficacy to provide patients with quality and affordable biologics.
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, autoimmune diseases and ophthalmic diseases. Up to date, 5 products have been launched in China, 1 in Europe, 13 indications approved worldwide, and 7 New Drug Applications (NDAs) accepted for review in China. 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 commercialization. It has established global innovation centers and Shanghai-based manufacturing facilities in line with global Good Manufacturing Practice (GMP), including Xuhui Plant certificated by China and the EU GMP and Songjiang First Plant certificated by China GMP.
Henlius has pro-actively built a diversified and high-quality product pipeline covering over 20 innovative monoclonal antibodies (mAbs) and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name in Europe: Zercepac®, trade names in Australia: Tuzucip® and Trastucip®), the first China-developed mAb biosimilar approved both in China and Europe, HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors and its NDA for the treatment of squamous non-small cell lung cancer and extensive small-cell lung cancer (ES-SCLC) are under review. What's more, Henlius has conducted over 20 clinical studies for 12 products and 11 combination therapies.
【参考文献】
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[3] Stockis J, Lienart S, etc. Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin alphaVbeta8. Proc Natl Acad Sci U S A. 2017; https://doi.org/10.1073/pnas.1710680114.
[4] Gordon KJ, Blobe GC. Role of transforming growth factor-beta super family signaling pathways in human disease. Biochim Biophys Acta. 2008;1782(4):197–228.
[5] Kulkarni AB, Karlsson S. Transforming growth factor-beta 1 knockout mice. A mutation in one cytokine gene causes a dramatic inflammatory disease. Am J Pathol. 1993;143(1):3–9.
[6] Li MO, Wan YY, etc. Transforming growth factorbeta regulation of immune responses. Annu Rev Immunol. 2006; 24:99–146.
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