2022年2月14日，复宏汉霖（2696.HK）宣布，公司自主开发的重组人源抗PD-L1与抗TIGIT双特异性抗体HLX301在局部晚期或转移性实体瘤患者中的I期临床研究在澳大利亚完成首例受试者给药。
T细胞免疫球蛋白和ITIM结构域（T cell immunoglobulin and ITIM domain，TIGIT）是一种抑制性受体，在淋巴细胞中表达，包括自然杀伤（NK）细胞、活化的CD8+ T和CD4+ T细胞以及Treg（调节性T细胞）等。作为免疫检查点蛋白，TIGIT可通过多种作用机制抑制固有和适应性免疫，在肿瘤免疫抑制中的“踩刹车”作用和PD-1/PD-L1类似。临床前研究结果表明，对比抗PD-L1单抗、抗TIGIT单抗以及两种单抗的联合疗法，HLX301可与人PD-L1和TIGIT特异性结合并同时阻断PD-1/PD-L1和TIGIT/PVR负向信号通路，抑制肿瘤细胞的生长，且耐受性、安全性良好，充分体现了双抗疗法的协同增强效应，有望用于多种晚期肿瘤的治疗，包括非小细胞肺癌、头颈部鳞状细胞癌、食管鳞癌等。目前，全球范围内尚无同类靶向PD-1/L1和TIGIT的双特异性抗体获批上市，且HLX301在同类靶向PD-L1×TIGIT双特异性抗体中率先完成首例受试者用药，有望成为first-in-class抗PD-L1×TIGIT双抗。
复宏汉霖不断深耕未满足的临床需求，目前已打造出多元化的创新药候选产品管线，在PD-1/L1、LAG-3、TIGIT、BRAF等创新靶点全面布局，并积极开展双特异性抗体、抗体偶联药物（ADC）等产品的开发。复宏汉霖正积极加速向创新型Biopharma进化，提高创新效率，加强优质创新资产的引进和合作，“内外兼修”，为全球患者带去高质量、可负担的创新治疗方案。
关于该HLX301 I期临床研究
本研究是一项在既往标准治疗失败、不耐受或无合适标准治疗的局部晚期或转移性实体瘤患者中开展的，旨在评估HLX301的安全性、耐受性、药代动力学及初步抗肿瘤疗效的开放、多中心、剂量探索、首次人体I期临床试验。合格的受试者将接受每两周静脉输注单药HLX301的治疗。Ia期为剂量递增阶段，主要终点为评估HLX301的安全性、剂量限制毒性（DLT），并确定最大耐受剂量（MTD）；次要终点包括药代动力学、药效动力学和免疫原性。Ib期为剂量拓展阶段，主要终点为II期临床试验推荐剂量（RP2D）；次要终点包括客观缓解率（ORR）、疾病控制率（DCR）和持续缓解时间（DOR）。
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4款产品，在欧盟上市1款产品，3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研发中心，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，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单抗斯鲁利单抗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®）、汉达远®（阿达木单抗）和汉贝泰®（贝伐珠单抗）相继获批上市，创新产品斯鲁利单抗MSI-H实体瘤的上市注册申请已纳入优先审评审批程序，HLX01利妥昔单抗类风湿关节炎新适应症、斯鲁利单抗鳞状非小细胞肺癌适应症的上市注册申请也正在审评中。公司亦同步就12个产品、9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。
First Subject Dosed in the Australia Phase 1 Trial of Henlius' Potential First-In-Class Anti PD-L1×TIGIT Bispecific Antibody
Shanghai, China, February 14th, 2022-Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the first patient has been dosed in Australia in the Phase 1 clinical trial of HLX301, a recombinant humanized anti-PD-L1 and anti-TIGIT bispecific antibody (BsAb), for the treatment of locally advanced or metastatic solid tumours.
TIGIT (T cell immunoreceptor with immunoglobulin and ITIM domains) is an inhibitory receptor, mainly expressed on natural killer (NK) cells and activated CD8+ T cells, CD4+ T cells, and T regulatory cells. As an inhibitory receptor, TIGIT can inhibit innate and adaptive responses in various mechanisms of action and act as a “brake” like PD-1/PD-L1 does to stop T cells from attacking tumours. Pre-clinical studies reported that HLX301 can simultaneously block both PD-1/PD-L1 and TIGIT/PVR pathways, restore TCR signaling, inhibit tumour growth, and has good tolerance and safety, paving the way for further clinical development to against a variety of advanced cancers, including non-small cell lung cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, etc. At present, no BsAb targeting PD-1/PD-L1 and TIGIT has been approved for marketing globally. As the first to be dosed in the subject, HLX301 is expected to be a first-in-class anti-PD-L1×TIGIT BsAb.
Underpinned by the patient-centric strategy, Henlius has built an innovative product pipeline with many emerging targets, including PD-1/L1, LAG-3, TIGIT, BRAF, etc. and has been developing a forward-looking presence in bispecific antibodies and the antibody-drug conjugates (ADC). Looking forward, Henlius is actively accelerating the evolution to an innovative Biopharma and improving efficiency through innovations, and will continue its momentum for innovation, further strengthening the in-licensing and collaboration on external innovative assets, and bringing more high-quality and affordable therapies to patients worldwide.
About HLX301 Phase 1 Trial
This open-label, multicentre, dose-finding, first-in-human phase 1 study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumour efficacy of HLX301 in locally advanced or metastatic solid tumour patients who have failed prior standard treatment and are intolerant or ineligible to standard therapy. Eligible patients will receive intravenous infusion of HLX301 as a single agent every- two-week. Phase 1a is a dose escalation study. The primary endpoints are to evaluate the safety, dose limiting toxicity (DLT), and determine the maximum tolerated dose (MTD) of HLX301. Secondary endpoints include pharmacokinetic, pharmacodynamic and immunogenicity. Phase 1b is a dose expansion study. The primary endpoint is to determine the recommended phase 2 dose (RP2D). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), and duration of response (DOR).
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, 4 products have been launched in China, 1 in the European Union (EU), 3 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 commercialisation. It has established global R&D centres 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 serplulimab (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, 汉达远® (adalimumab) and 汉贝泰® (bevacizumab), the NDA of innovative product serplulimab indicated for MSI-H solid tumors has been granted priority review, and the NDAs of HLX01 (rituximab) for the treatment of rheumatoid arthritis and serplulimab for the treatment of squamous non-small cell lung cancer are also under review. What's more, Henlius has conducted over 20 clinical studies for 12 products and 9 combination therapies worldwide, expanding its presence in major market as well as emerging market.
