复宏汉霖免疫检查点抑制剂又添新成员，创新型抗LAG-3单抗IND申请获NMPA批准
2021年4月15日，复宏汉霖（2696.HK）宣布，公司自主开发的HLX26（重组抗LAG-3人源化单克隆抗体注射液）的临床试验申请获得国家药品监督管理局（NMPA）批准，有望用于实体瘤及淋巴瘤的治疗。
淋巴细胞活化基因3（Lymphocyte-activation gene 3，LAG-3）是一种免疫检查点受体蛋白，被视为继PD-1/L1、CTLA-4后新一代的免疫治疗靶点，全球目前暂无该靶点产品上市。多项临床研究数据显示，LAG-3抑制剂在肺癌、乳腺癌、黑色素瘤和头颈癌等多种实体瘤和血液肿瘤中均有明显的疾病控制效果，已有III期临床研究显示其与PD-1抑制剂联用可协同增强免疫应答，具有广阔的肿瘤治疗应用前景。
LAG-3主要在活化的T细胞和部分NK细胞等人体免疫细胞表面表达，与配体结合后，对T细胞的增殖、活化和稳态等起负调节作用-1。HLX26作为靶向LAG-3胞外结构域的人源化单抗，可阻断LAG-3介导的负信号通路，使T细胞重新获得细胞毒性活性，从而恢复对肿瘤的杀伤功能。临床前研究表明，HLX26具有抗肿瘤活性以及良好的耐受性和安全性，尤其是在体外实验和动物模型中，HLX26与公司创新型PD-1抑制剂HLX10联用显示出了明显的肿瘤抑制作用，具有协同效应。临床前研究结果为HLX26后续开展临床试验提供了科学依据，该产品有望在实体瘤和淋巴瘤治疗领域发挥重要作用，拓展公司疾病治疗领域。
目前，复宏汉霖已在PD-1/L1、CTLA-4、LAG-3等免疫检查点全面布局，为免疫联合治疗的探索创造更多可能。未来公司将依托丰富的靶点开发经验和一体化研发平台，积极开发更多被市场所需要的创新型产品，打造出高质量、可负担且具有差异化优势的创新产品管线。
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3款产品，在欧盟上市1款产品，2款产品获得中国上市注册申请受理。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。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，欧盟商品名：Zercepac®）、公司首个自身免疫疾病治疗产品汉达远®（阿达木单抗）相继获批上市，公司HLX04贝伐珠单抗及HLX01利妥昔单抗类风湿关节炎新适应症的上市注册申请也正在审评中。公司亦同步就10个产品、8个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国家市场
Henlius Received IND Approval for Its Novel Anti-LAG-3 mAb HLX26 from NMPA
Shanghai, China, April 15, 2021 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug (IND) application of its HLX26 (recombinant anti-LAG-3 human monoclonal antibody injection) has been approved by the National Medical Products Administration (NMPA) for treatment of solid tumors and lymphomas.
Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint receptor and is regarded as a new generation of immunotherapy target after PD-1/L1 and CTLA-4. Currently, there is no LAG-3 targeted product on the market around the globe. A number of clinical studies have shown that LAG-3 inhibitors have obvious disease control effects in many solid tumors and hematological malignancy such as lung cancer, breast cancer, melanoma, head and neck cancer. A Phase III clinical study suggests that targeting the LAG-3 pathway in the combination with PD-1/L1 pathway effectively activates immune response, demonstrating the promising prospect of this product.
LAG-3 is an immune checkpoint receptor that is mainly expressed on human immune cells including activated T cells and part of NK cells, and negatively regulats the proliferation, activization and homeostasis of T cells-1. HLX26 is a human mAb targeting LAG-3 extracellular domains, can block the LAG-3-mediated signaling pathway to restore the killing function of T-cell. Pre-clinical studies have proved that HLX26 has anti-tumor effect and favourable tolerability and safety. Particular in in vitro and animal model studies, HLX26 combined with Henlius’ proprietary anti-PD-1 mAb HLX10 creates synergistic effects in anti-tumor. These results lay the foundation for further clinical studies. HLX26 is expected to play an important role in the treatment of solid tumors and lymphomas, and expand the Company’s therapeutic area.
At present, Henlius has built an all-round layout of the immune checkpoint products of PD-1/L1, CTLA-4 and LAG-3, etc., creating more opportunities for the exploration of combination immunotherapy. Looking forward, the Company will rely on extensive target development experience and integrated R&D platform actively developing more innovative products for patients, and build a high-quality, affordable and differentiated innovative product pipeline.
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, 3 products have been launched in China, 1 in the European Union (EU), the New Drug Applications (NDA) of 2 products 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 commercialisation. It has established global R&D centers and a Shanghai-based manufacturing facility certificated by China and the EU Good Manufacturing Practice (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 HLX10 (anti-PD-1 mAb) as backbone. Apart from the launched products 汉利康® (rituximab), the first China-developed biosimilar, 汉曲优® (trastuzumab, Zercepac® in the EU), the first China-developed mAb biosimilar approved both in China and in the EU and 汉达远® (adalimumab), the Company's first product indicated for autoimmune diseases, the NDA of HLX04 (bevacizumab) and HLX01 (rituximab) for the treatment of rheumatoid arthritis are under review. What's more, Henlius has conducted over 20 clinical studies for 10 products and 8 combination therapies worldwide, expanding its presence in major market as well as emerging market.
【参考文献】
[1] Ruffo E, Wu R C, Bruno T C, et al. Lymphocyte-activation gene 3 (LAG3): the next immune checkpoint receptor[C]//Seminars in immunology. Academic Press, 2019, 42: 101305.
[2] Solinas C, Migliori E, De Silva P, et al. LAG3: the biological processes that motivate targeting this immune checkpoint molecule in human cancer[J]. Cancers, 2019, 11(8): 1213.