A Phase I, Randomized, Double-Blind, Placebo-Controlled, Escalating Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Epsi- Gam in Healthy, Cat-, Dust Mite-, or Bermuda Grass-Allergic Subjects

This is a single-center, randomized, double-blind, placebo-controlled, single-dose, dose- escalation study in otherwise healthy cat-, dust mite-, or Bermuda grass-allergic male and female subjects. There will be five dosing cohorts (0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg), with eight subjects in each cohort, randomized to either epsi-gam (6 subjects) or placebo (2 subjects) for a total of 40 subjects. The first cohort will receive the starting dose of 0.1 mg/kg epsi-gam or placebo and subsequent cohorts will be recruited sequentially to receive escalating doses of epsi-gam or placebo.

开始日期2015-08-01

申办/合作机构

Tunitas Therapeutics, Inc.

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100 项与 Epsi-gam 相关的临床结果

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100 项与 Epsi-gam 相关的转化医学

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100 项与 Epsi-gam 相关的专利（医药）

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项与 Epsi-gam 相关的文献（医药）

2024-07-01·Antiviral Research

Development of nanoparticle vaccines utilizing designed Fc-binding homo-oligomers and RBD-Fc of SARS-CoV-2

Article

作者: Zhao, Jun ; Dong, Jinhua ; Wang, Yuhui ; Xiao, Weiling ; Liu, Zhijun ; Zhang, Shengshuo ; Zhang, Mengtao ; Yu, Bowen ; Liang, Yucai ; Peng, Yuan

The Fc-fused receptor binding domain (RBD-Fc) vaccine for SARS-CoV-2 has garnered significant attention for its capacity to provide effective and specific immune protection. However, its immunogenicity is limited, highlighting the need for improvement in clinical application. Nanoparticle delivery has been shown to be an effective method for enhancing antigen immunogenicity. In this study, we developed bivalent nanoparticle recombinant protein vaccines by assembling the RBD-Fc of SARS-CoV-2 and Fc-binding homo-oligomers o42.1 and i52.3 into octahedral and icosahedral nanoparticles. The formation of RBD-Fc nanoparticles was confirmed through structural characterization and cell binding experiments. Compared to RBD-Fc dimers, the nanoparticle vaccines induced more potent neutralizing antibodies (nAb) and stronger cellular immune responses. Therefore, using bivalent nanoparticle vaccines based on RBD-Fc presents a promising vaccination strategy against SARS-CoV-2 and offers a universal approach for enhancing the immunogenicity of Fc fusion protein vaccines.

2024-03-01·Biotechnology Reports

Immunogenicity of a recombinant plant-produced respiratory syncytial virus F subunit vaccine in mice

Article

作者: Pisuttinusart, Nuttapat ; Ketloy, Chutitorn ; Srisaowakarn, Chanya ; Prompetchara, Eakachai ; Phoolcharoen, Waranyoo ; Shanmugaraj, Balamurugan ; Thitithanyanont, Arunee

Respiratory syncytial virus (RSV) is a highly infectious respiratory virus that causes serious illness, particularly in young children, elderly people, and those with immunocompromised individuals. RSV infection is the leading cause of infant hospitalization and can lead to serious complications such as pneumonia and bronchiolitis. Currently, there is an RSV vaccine approved exclusively for the elderly population, but no approved vaccine specifically designed for infants or any other age groups. Therefore, it is crucial to continue the development of an RSV vaccine specifically tailored for these populations. In this study, the immunogenicity of the two plant-produced RSV-F Fc fusion proteins (Native construct and structural stabilized construct) were examined to assess them as potential vaccine candidates for RSV. The RSV-F Fc fusion proteins were transiently expressed in Nicotiana benthamiana and purified using protein A affinity column chromatography. The recombinant RSV-F Fc fusion protein was recognized by the monoclonal antibody Motavizumab specific against RSV-F protein. Moreover, the immunogenicity of the two purified RSV-F Fc proteins were evaluated in mice by formulating with different adjuvants. According to our results, the plant-produced RSV-F Fc fusion protein is immunogenic in mice. These preliminary findings, demonstrate the immunogenicity of plant-based RSV-F Fc fusion protein, however, further preclinical studies such as antigen dose and adjuvant optimization, safety, toxicity, and challenge studies in animal models are necessary in order to prove the vaccine efficacy.

2023-06-01·Inflammopharmacology

Human TFF2-Fc fusion protein alleviates DSS-induced ulcerative colitis in C57BL/6 mice by promoting intestinal epithelial cells repair and inhibiting macrophage inflammation

Article

作者: Wei, Jianteng ; Lu, Xuxiu ; Wang, Rongrong ; Guo, Meng ; Liu, Ming ; Liu, Mingfei ; Li, Zhen ; Geng, Jiajia

The clinical drugs for ulcerative colitis mainly affect the inflammatory symposiums with limited outcomes and various side effects. Repairing the damaged intestinal mucosa is a promising and alternative strategy to treat ulcerative colitis. Trefoil factor family 2 (TFF2) could repair the intestinal mucosa, however, it has a short half-life in vivo. To improve the stability of TFF2, we have prepared a new fusion protein TFF2-Fc with much stability, investigated the therapeutic effect of TFF2-Fc on ulcerative colitis, and further illustrated the related mechanisms. We found that intrarectally administered TFF2-Fc alleviated the weight loss, the colon shortening, the disease activity index, the intestinal tissue injury, and the lymphocyte infiltration in dextran sulfate sodium (DSS)-induced colitis mice. In vitro, TFF2-Fc inhibited Caco2 cells injury and apoptosis, promoted cellular migration, and increased the expression of Occludin and ZO-1 by activating P-ERK in the presence of H₂O₂ or inflammatory conditioned medium (LPS-RAW264.7/CM). Moreover, TFF2-Fc could reduce lipopolysaccharide (LPS)-induced production of inflammation cytokines and reactive oxygen species in RAW264.7 cells, and also inhibits the polarization of RAW264.7 cells to M1 phenotype by reducing glucose consumption and lactate production. Taken together, in this work, we have prepared a novel fusion protein TFF2-Fc, which could alleviate ulcerative colitis in vivo via promoting intestinal epithelial cells repair and inhibiting macrophage inflammation, and TFF2-Fc might serve as a promising ulcerative colitis therapeutic agent.

项与 Epsi-gam 相关的新闻（医药）

2024-11-05

·复宏汉霖

差异化的分子作用机制，抗体领域权威期刊mAbs发表H药斯鲁利单抗最新研究结果

近日，复宏汉霖针对创新型抗PD-1单抗H药（汉斯状®，斯鲁利单抗）作用机制的研究结果在抗体领域权威期刊mAbs成功发表。研究结果揭示了斯鲁利单抗发挥优异疗效的差异化分子机制。同时，研究发现，相较斯鲁利单抗单药治疗，斯鲁利单抗与复宏汉霖自研抗TIGIT Fc融合蛋白HLX53及抗LAG-3单抗HLX26等免疫检查点抑制剂的双免疫疗法可进一步提高抗肿瘤疗效，有望为肿瘤患者带来更高效的临床治疗选择。近年来，免疫检查点抑制剂的开发促进了肿瘤免疫治疗的快速发展。免疫检查点是维持免疫应答、保护正常组织的关键蛋白分子，但也会被肿瘤细胞利用，逃避免疫系统的监测和攻击[1-3]。其中，以抗PD-1/L1抗体为代表的免疫检查点抑制剂，可通过阻断PD-1/L1信号通路，恢复免疫系统对肿瘤细胞的杀伤能力，已广泛应用于多类恶性肿瘤的临床治疗[4]。H药汉斯状®为复宏汉霖自主研发的重组人源化抗PD-1单抗注射液，目前已被批准用于治疗微卫星高度不稳定（MSI-H）实体瘤、鳞状非小细胞肺癌（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）和食管鳞状细胞癌（ESCC）4项适应症，惠及逾80,000患者。基于斯鲁利单抗在小细胞肺癌的治疗中展现出优异疗效，H药成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。相关研究结果显示，H药斯鲁利单抗具有与Pembrolizumab相近的结合表位，但其在重链和轻链的空间利用方式上较为独特，或将促成了斯鲁利单抗与PD-1受体间差异化的相互作用。此外，鉴于独特的识别模式，斯鲁利单抗相对同类PD-1抑制剂而言展现出较高的人PD-1亲和力水平（KD=2.42 nM)，且拥有较强的PD-1内吞活性，减少T细胞表面留存的PD-1受体数目[5]。为进一步探索斯鲁利单抗的分子作用机制，本研究分析了PD-1/L1信号通路上关键蛋白的表达水平。研究结果显示，斯鲁利单抗能够减少PD-1对免疫共刺激分子CD28的募集，从而减少磷酸化酶SHP2对CD28的去磷酸化作用，更大程度保留CD28传递的信号[6-8]，因此，斯鲁利单抗进一步提高了信号通路下游AKT蛋白的活性[9]，促进T细胞的持续、稳健活化。与此同时，研究者进一步探索了斯鲁利单抗、Pembrolizumab等抗PD-1单抗协同其他免疫检查点抑制剂的双免疫联合疗法的抗肿瘤疗效。研究结果显示，斯鲁利单抗联合 HLX53（抗TIGIT Fc融合蛋白）能够双重阻断 PD-1/TIGIT信号传导，在抗肿瘤活性（TGI/生存率）上优于PD-1抑制剂单药疗法，且斯鲁利单抗/HLX53联合治疗组较Pembrolizumab/HLX53潜在抗肿瘤活性更高。与Pembrolizumab 和Tiragolumab（抗TIGIT抗体）的联合疗法相比，斯鲁利单抗联合HLX53能够显著增强效应CD4+T细胞、CD8+T细胞等免疫细胞在肿瘤内的浸润。此外，一系列研究数据表明，与Pembrolizumab/HLX53或Pembrolizumab/Tiragolumab联合疗法相比，斯鲁利单抗/HLX53的联合疗法对肿瘤微环境的诱导作用更强，有利于调动免疫细胞将 “冷 ”肿瘤变为 “热 ”肿瘤（SCLC通常被认为是一种免疫冷肿瘤），从而提高肿瘤免疫疗法的疗效。除TIGIT抑制剂外，斯鲁利单抗联合 HLX26（抗LAG-3单抗）也呈现出较单药治疗更强的抗肿瘤活性，有望进一步放大斯鲁利单抗作为免疫基石药物的治疗优势。未来，复宏汉霖将继续以临床需求为导向，进一步拓展H药差异化、多维度的临床布局；同时，基于丰富的自研管线，积极探索H药与自有单抗产品、化疗等治疗手段开展联合治疗，充分挖掘免疫疗法的治疗潜力，为全球患者带去高品质、可负担的创新治疗方案。关于mAbs mAbs 为多学科开放获取期刊，专攻抗体工艺技术的研究与开发。该杂志聚焦科学和医学领域，读者群体广泛，包括：科学家、临床研究人员和医生，以及技术转让、法规、投资、疗法规划规范等方面的专家。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，已有6款产品在中国获批上市，3款产品在国际获批上市，24项适应症获批，4个上市申请分别获中国药监局、美国FDA和欧盟EMA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，公司商业化生产基地已相继获得中国、欧盟和美国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50多个分子，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。截至目前，公司已获批上市产品包括国内首个生物类似药汉利康®（利妥昔单抗）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、汉达远®（阿达木单抗）、汉贝泰®（贝伐珠单抗）以及汉奈佳®（奈拉替尼），此外，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、鳞状非小细胞肺癌、广泛期小细胞肺癌和食管鳞状细胞癌，并成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。公司亦同步就16个产品在全球范围内开展30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。 Latest Research into the Differentiated Mechanisms of Action of Serplulimab Published in mAbs Journal Recently, the preclinical study results of serplulimab, Henlius’ innovative anti-PD-1 monoclonal antibody (mAb) were published in antibody R&D focus journal mAbs. The study revealed insights into the possible mechanisms underlying the excellent efficacy of serplulimab. Furthermore, the study found that the combined treatment with serplulimab and another immune checkpoint inhibitor, such as Henlius’ innovative anti-TIGIT Fc fusion protein HLX53 and anti-LAG-3 mAb HLX26, enhanced anti-tumour activity compared with serplulimab alone, which shows promise of more efficient clinical treatment options for cancer patients. In recent years, the research into immune checkpoint inhibitors has facilitated the rapid development of tumour immunotherapy. Immune checkpoints are crucial proteins in maintaining the immune response and protecting normal tissues. Nevertheless, these molecules may also be exploited by tumour cells to evade immune surveillance[1-3]. Immune checkpoint inhibitors represented by anti-PD-1/L1 antibodies can restore the immune system's anti-tumour activity by blocking the binding of immune checkpoints to their ligands, and have been widely used for the treatment of various types of malignant tumuors[4]. Serplulimab (HANSIZHUANG) is a recombinant humanised anti-PD-1 mAb injection independently developed by Henlius, and the world's first anti-PD-1 mAb approved for the first-line treatment of small cell lung cancer (SCLC). Up to date, HANSIZHUANG has been approved by China’s National Medical Products Administration for the treatment of microsatellite instability-high (MSI-H) solid tumours, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC), benefiting approximately 80,000 patients. Based on its outstanding therapeutic efficacy in the treatment of small cell lung cancer (SCLC), serplulimab has became the world's first anti-PD-1 mAb approved for the treatment of SCLC. According to related research results, serplulimab targeted against a similar binding epitope compared with that targeted by pembrolizumab, while the spatial organisation of the heavy and light chains of serplulimab is unique, which may contribute to the different spatial interaction between serplulimab and PD-1 receptor. Moreover, due to its unique mode of recognition, serplulimab exhibits higher affinity (KD=2.42 nM) than other PD-1 inhibitors and robustly induces PD-1 receptor endocytosis, resulting in reduction of PD-1 receptors retained on the surface of T cells[5]. To further investigate the molecular mechanism of serplulimab, researchers analysed the expression level of key modulators on PD-1/L1 signalling pathway. The results showed that, serplulimab reduced the recruitment of immune co-stimulatory receptor CD28 by PD-1, thereby decreasing the dephosphorylation of CD28 mediated by phosphatase SHP2 and retaining the signal transmitted by CD28[6-8]. Further downstream the signalling pathway, the activity of protein kinase AKT was enhanced[9], thereby promoting sustained activation of T cells. Moreover, the researchers examined the anti-tumour activity of a PD-1 inhibitor, such as serplulimab or pembrolizumab, in combination with another immune checkpoint inhibitor. The results suggest that compared with serplulimab alone, combined treatment with serplulimab/HLX53 (anti-TIGIT Fc protein) resulted in dual PD-1/L1-TIGIT blockade and greater tumour growth inhibition(TGI) and survival rate reduction. Also, the serplulimab/HLX53 combination demonstrated higher potential as an immunotherapy compared with pembrolizumab/HLX53. Specifically, serplulimab/HLX53 significantly promoted the infiltration of effector CD4+ T cells and effector CD8+ T cells within tumours versus pembrolizumab/tiragolumab (an anti-TIGIT mAb). In addition, a series of analysis and data suggest that serplulimab/HLX53 induced strong modulation on the tumour microenvironment, mobilising immune cells to turn “cold” tumours into “hot” ones to improve the efficacy of anti-tumour immunotherapy (SCLC is often considered an immune-cold tumour). In addition, the serplulimab/HLX26 combination also enhanced anti-tumour activity compared with their respective monotherapies, which may further amplify the therapeutic advantages of serplulimab as an immune cornerstone product. Looking forward, Henlius will further expand HANSIZHUANG’s differentiated and multi-dimensional layout underpinned by the patient-centric strategy. Meanwhile, the company will actively promote HANSIZHUANG in combination with in-house products of Henlius and chemotherapy drugs to conduct immune combination therapies in a wide variety of indications, committing to bringing affordable and high-quality innovative treatments to patients around the world. About mAbs mAbs is a multidisciplinary, open access journal dedicated to the art and science of antibody research and development. The journal has a strong scientific and medical focus but serves a broad readership, including specialists in technology transfer, legal issues, investment, planning and the regulation of therapeutics. 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, 6 products have been launched in China, 3 have been approved for marketing in overseas markets, 24 indications are approved worldwide, and 4 marketing applications have been accepted for review in China,the US and the EU, respectively. 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 centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP. Henlius has pro-actively built a diversified and high-quality product pipeline covering over 50 molecules 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: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab), HANBEITAI (bevacizumab) and HANNAIJIA (neratinib), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. What’s more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets. 参考文献 1. Ai L, et al. Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond. Adv Exp Med Biol. 2020; 1248:33-59. 2. Latchman Y, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2(3):261-268. 3. Dong H, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion [published correction appears in Nat Med 2002 Sep;8(9):1039]. Nat Med. 2002;8(8):793-800. 4. Curran MA. Preclinical Data Supporting Antitumor Activity of PD-1 Blockade. Cancer J. 2018;24(1):2-6. 5. Issafras H, et al. Structural basis of HLX10 PD-1 receptor recognition, a promising anti-PD-1 antibody clinical candidate for cancer immunotherapy. PLoS One. 2021;16(12):e0257972. 6. Hui E, et al. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science. 2017;355(6332):1428-1433. 7. Patsoukis N, et al. Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation. Commun Biol. 2020;3(1):128. 8. Fenwick C, et al. Tumor suppression of novel anti-PD-1 antibodies mediated through CD28 costimulatory pathway. J Exp Med. 2019;216(7):1525-1541. 9. Primavera E, et al. Computer-Aided Identification of Kinase-Targeted Small Molecules for Cancer: A Review on AKT Protein. Pharmaceuticals (Basel). 2023;16(7):993. 联系方式媒体：PR@Henlius.com 投资者：IR@Henlius.com 喜欢本文内容点击下方按钮·分享 ·收藏 ·点赞 ·在看

免疫疗法临床结果

2024-08-26

·复宏汉霖

复宏汉霖2024半年度业绩：以患者为中心，稳健可持续增长，出海打开发展新空间

2024年8月26日，复宏汉霖（2696.HK）发布2024年度中期业绩，于业绩期内实现营业收入约人民币27.461亿元，较去年同期增长约9.8%，净利润约人民币3.863亿元，较去年同期增长约61.0%，多款核心商业化产品赋能业绩持续增长，实现产品销售收入24.794亿元，保持高质量盈利。汉曲优®（美国商品名：HERCESSI™，欧洲商品名：Zercepac®）和H药汉斯状®分别实现销售收入约14.743亿元及6.778亿元。同时，公司加速拓展全球商业化版图，挖掘海外市场增长潜力，为长期高质量发展注入澎湃动能。截至目前，复宏汉霖已有6款产品在中国上市，3款产品在全球获批上市，24项适应症获批，触达48个国家和地区，广泛覆盖亚洲、欧洲、拉丁美洲、北美洲和大洋洲，并惠及逾60万名患者。业绩期内，公司完成近80项药政注册申请，并收获60余项药政注册批准，覆盖中国、美国、欧盟、加拿大、印尼和日本等国家和地区，加速产品全球化进程。同时，公司秉持差异化的创新策略，持续丰富并优化产品管线，布局50余个分子和14个研发平台，药物形式覆盖单抗、多抗、抗体偶联药物、融合蛋白、小分子药物等。复宏汉霖董事长、执行董事张文杰表示： 2024上半年，复宏汉霖完善的商业化布局和策略效益凸显，继2023年首次年度盈利后，公司实现了持续盈利和稳健增长，开启了崭新的发展篇章。展望未来，复宏汉霖将进一步激发创新动能，以更加积极的姿态应对外界变化。同时，持续深化精益管理和运营体系，着力加固企业发展护城河，向成为高质量发展的国际化创新生物制药企业的目标继续迈进。复宏汉霖执行董事、首席执行官朱俊表示：创新和国际化是引领我们持续前行，不断解决未满足的临床需求的两大核心策略。2024上半年，复宏汉霖全球商业化版图再度刷新，出海之路硕果累累，我们的创新蓄水池加速扩增，差异化创新优势进一步夯实。未来，我们将继续坚持‘以患者为中心’的理念，专注于开发具有临床价值的突破性治疗方案，加速惠及全球更多患者。全球化布局：出海高歌猛进，商业化空间广阔 2024年上半年，复宏汉霖继续高效推动研产销一体化发展，并不断完善管理体系提升商业化运营效率，通过多维提升产品可及性、探索业态多元化等举措，促进核心产品的商业化增长实现持续高质量盈利。与此同时，公司在全球市场的扩展上取得重要新突破，多个新市场的获批准入和实现销售为公司海外市场增长带来新活力。业绩期内，公司5款产品销售收入合计约人民币24.794亿元，同比增长15.2%。其中，汉曲优®（美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、H药汉斯状®（斯鲁利单抗）和汉贝泰®（贝伐珠单抗）于2024上半年分别实现销售收入人民币14.743、6.778、0.867亿元。此外，基于与合作伙伴的约定，公司就汉利康®（利妥昔单抗）、汉达远®（阿达木单抗）分别实现销售收入约人民币2.270亿元和0.136亿元。公司核心抗肿瘤产品汉曲优®持续保持良好增长势头，2024年上半年达成全球销售收入约人民币14.743亿元，同比增长15.5%。截至目前，该产品已在全球48个国家和地区获批，覆盖亚洲、欧洲、拉丁美洲、北美洲和大洋洲，为获批上市国家和地区最多的国产单抗生物类似药，累计惠及超过200,000名患者。其中，汉曲优®国内市场份额不断攀升，2024上半年实现销售额约人民币14.062亿元，较去年同期增长约13.5%。凭借差异化的临床用药优势和历经验证的国际品质，汉曲优®逐步获得医生、患者及行业等多方认可，成为国内曲妥珠单抗的领导品牌。同时，汉曲优®在海外市场高歌猛进，于业绩期内实现销售收入约0.682亿元，同比增长79.1%。2024年4月，汉曲优®在美国获批上市，成为中美欧三地获批的国产单抗生物类似药；并于2024年6月成功发货沙特，有望成为首个登陆中东市场的国产单抗生物药。此外，截至2024年8月，汉曲优®还新增加拿大、菲律宾、巴西、乌兹别克斯坦、土库曼斯坦等市场获批上市，推动更多患者获益。 H药汉斯状®是全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，已在中国、印尼、柬埔寨、泰国等地获批上市。2024年上半年，汉斯状®实现销售收入约6.778亿元，同比增长21.8%。目前，H药已有4项适应症获批，广泛覆盖肺癌、消化道肿瘤等高发肿瘤，累计惠及逾7.5万名患者。该产品第5项适应症一线治疗非鳞状非小细胞肺癌（nsNSCLC）的上市注册申请也已获中国国家药监局（NMPA）受理，有望在今年下半年获批。2024年上半年，H药在海外市场实现销售及授权许可收入约0.752亿元。截至目前，H药对外授权已覆盖美国、欧洲、东南亚、中东和北非、印度等70多个国家和地区，并成为首个登陆东南亚国家的国产抗PD-1单抗。2024年第一季度，公司高效完成H药的首批海外发货，开启了该产品惠及全球患者的新篇章。此外，H药一线治疗ES-SCLC的欧盟上市许可申请（MAA）已获得欧洲药品管理局 (EMA) 受理，有望于2024年获批上市。公司亦于新加坡、马来西亚等国家递交了H药上市许可申请。同时，公司还稳步推进H药对比一线标准治疗阿替利珠单抗用于治疗ES-SCLC的头对头美国桥接试验，并计划于2025年初递交H药在美国的生物制品许可申请（BLA）。 2024年上半年，复宏汉霖商业合作再迎多个里程碑。公司与Sermonix就临床阶段在研新型乳腺癌内分泌疗法HLX78（拉索昔芬）达成亚洲区域合作。同时，公司与甫康药业就汉奈佳®（奈拉替尼）达成商业化合作，进一步丰富公司乳腺癌治疗产品管线，该产品能够与汉曲优®实现序贯治疗，有望进一步降低HER2阳性早期乳腺癌患者复发风险。公司亦携手Accord、Eurofarma、KGbio、Organon等国际合作伙伴加速推进更多产品在全球的上市注册进程。业绩期内，汉利康®于秘鲁获批，成为公司第三款海外获批上市的自主研发和生产的产品。与此同时，HLX14（地舒单抗生物类似药）在欧盟的上市申请已于2024年5月获得受理，有望于2025年获得上市批准。公司亦计划于2024下半年分别递交HLX14在美国的上市许可申请，及HLX11（帕妥珠单抗生物类似药）在中国和美国的上市许可申请。协同化发展：加速扩增创新蓄水池，国际品质护航生产 2024上半年，秉持可负担的创新这一初心，复宏汉霖持续完善和拓展差异化的创新管线，积极布局更广泛的疾病领域和新分子类型。聚焦临床需求，公司积极推进H药、HLX22（抗HER2单抗）、HLX42（EGFR靶向ADC）、HLX6018（抗GARP/TGF-β1单抗）等创新产品的临床开发进程。业绩期内，H药联合贝伐珠单抗及化疗一线治疗结直肠癌的国际多中心III期临床研究获日本药品医疗器械综合机构（PMDA）许可，并完成全球首例患者给药。引领HER2双靶向疗法，HLX22联合曲妥珠单抗及化疗一线治疗HER2阳性晚期胃癌的国际多中心III期临床研究申请获得美国食药监局（FDA）许可。同时，H药、HLX22等创新产品的多项研究结果亦登上AACR、ASCO、ASCO GI、ESMO GI、ENCALS等国际学术会议和Cancer Cell、Med等国际知名期刊。2024上半年，公司潜在FIC/BIC 的创新型EGFR靶向ADC HLX42、慢性炎症性疾病领域首款创新产品HLX6018成功完成首例受试者给药。双免疫联合抗血管靶向疗法--HLX53（抗TIGIT Fc融合蛋白）联合H药及贝伐珠单抗亦获NMPA批准并完成II期临床试验的首例患者给药，拟用于局部晚期或转移性肝细胞癌的一线治疗。在加码创新的同时，国际领先的高品质生产能力助力公司实现全球商业化布局，为将研发成果转化为普惠患者的社会价值提供重要保障。公司现有上海徐汇、松江（一）和松江（二）三大生产基地，松江基地（二）一期项目第一、二阶段两幢主要生产楼已完成包括原液、制剂生产线和首条预灌封系统（PFS）的设备安装调试及部分设备验证工作，一期项目第三阶段已完成主体结构封顶。目前公司商业化总产能达48,000升，已实现中国、欧洲、东南亚、拉美及中东等市场的稳定商业化供应。公司始终以国际化品质践行“汉霖质量”，其商业化生产基地及配套的质量管理体系已通过约百项由中国国家药监局、欧洲药品管理局（EMA）、美国食药监局（FDA）、欧盟质量受权人（QP）以及公司国际商业合作伙伴进行的多项实地核查及审计，获得中国、欧盟和美国GMP认证。公司积极推行精益项目运营，迭代升级生产工艺，以数字化建设赋能供应链、库存及质量管理，提质增效，把“可负担的创新，值得信赖的品质”落到实处。未来，聚焦患者未满足的临床需求，复宏汉霖将进一步夯实biopharma的商业化能力，不断提升研产销一体化平台的开发及运营效率，继续在创新与国际化的道路上加速疾驰，让更多、更高质量的创新成果惠及全球患者。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，已有6款产品在中国获批上市，3款产品在国际获批上市，24项适应症获批，3个上市申请分别获中国药监局和欧盟EMA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，公司商业化生产基地已相继获得中国、欧盟和美国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50多个分子，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。截至目前，公司已获批上市产品包括国内首个生物类似药汉利康®（利妥昔单抗）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、汉达远®（阿达木单抗）、汉贝泰®（贝伐珠单抗）以及汉奈佳®（奈拉替尼），此外，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、鳞状非小细胞肺癌、广泛期小细胞肺癌和食管鳞状细胞癌，并成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。公司亦同步就16个产品在全球范围内开展30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。 Henlius Maintains Patient-Centric Focus, Drives Sustainable Growth, and Accelerates Overseas Expansion in 2024 H1 Shanghai, China, August 26, 2024 – Henlius (2696.HK) announced its 2024 interim results. During the reporting period, Henlius’ revenue reached about RMB2.7461 billion, representing an increase of 9.8% YoY, and recorded a net profit of RMB386.3 million, up by 61.0% YoY. The solid and sustained profitability is due to increasing commercial sales of the company’s core products, which reached approximately RMB2.4794 billion. HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe) and HANSIZHUANG recorded sales of RMB1.4743 billion and RMB677.8 million, respectively. Meanwhile, the company accelerates the expansion of its global commercial footprint, unleashing the potential of overseas markets to promote its long-term high-quality development. Up to date, Henlius has 6 products launched in China, 3 approved for marketing in overseas markets, 24 indications approved worldwide, benefiting over 600,000 patients and reaching 48 markets in Asia, Europe, Latin America, North America and Oceania. During the reporting period, the company submitted approximately 80 drug registrations, and received more than 60 approvals in China, the U.S., EU, Canada, Indonesia and Japan. Meanwhile, the company stays focused on differentiated innovation to accelerate the development of products in its pipeline. Currently, its product pipeline covers more than 50 molecules and 14 R&D platforms with the forms of drug covering mAb, pAb, antibody-drug conjugate (ADC), fusion protein, and small molecule drug, etc. Wenjie Zhang, Chairman and Executive Director of Henlius, said:" In the first half of 2024, we have received impressive results based on our well-established commercial strategy and layout. Following the first time full-year profits in 2023, we achieved sustainable profitability and steady growth, opening a new chapter of high-quality development. Looking forward, we will further promote differentiated innovation and proactively respond to external changes. Meanwhile, we will continue to advance lean management and operations to solidify our leading position, progressing towards an innovative global biopharmaceutical company with a focus on high-quality development." Jason Zhu, Executive Director and Chief Executive Officer of Henlius, said:" Innovation and globalisation are two core strategies propelling us along the journey of addressing unmet clinical needs. In the first half of 2024, we have been actively expanding our global footprint with significant milestones achieved on our way of going abroad. Meanwhile, our innovation landscape has rapidly expanded, further strengthening our differentiated innovations. In the future, we will adhere to patient-centricity and stay committed to providing high-quality and innovative therapies to benefit more patients worldwide." Global Expansion: Swift Overseas Commercialisation & Vast Market Opportunities In the first half of 2024, Henlius continued to efficiently drive the integrated development of research, production, and commercialisation, while constantly improving commercial operational efficiency. Through multi-faceted measures such as improving product accessibility and exploring diversified business models, the company fostered the commercial growth of its core products, achieving sustained high-quality profitability. Furthermore, the company has achieved notable milestones in its global market expansion endeavors, with approvals and successful commercialisation across various markets infusing fresh momentum into the growth of its overseas presence. During the period, Henlius’ five products reached total sales revenue of approximately RMB2.4794 billion, up by 15.2% YoY. HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe), HANSIZHUANG (serplulimab), and HANBEITAI (bevacizumab) recorded sales of RMB1.4743 billion, RMB677.8 million and RMB86.7 million, respectively. In addition, the company received sales revenues of RMB227.0 million and RMB13.6 million based on the collaboration with partners for HANLIKANG (rituximab) and HANDAYUAN (adalimumab), respectively. Henlius' core oncology product HANQUYOU maintains a positive growth momentum. During the reporting period, HANQUYOU has recorded a global sales revenue of RMB1.4743 billion, up by 15.5% YoY. To date, HANQUYOU has been approved in 48 countries and regions around the world, covering Asia, Europe, Latin America, North America, and Oceania, making it the China-developed monoclonal antibody (mAb) biosimilar with the most marketing approvals, benefiting more than 200,000 patients. From which, HANQUYOU recorded domestic sales of RMB1.4062 billion, representing growth of 13.5%, further expanded its market share in China. Due to its differentiated clinical advantages and international recognised quality, HANQUYOU has been widely used in clinical practice and achieved rapid market acceptance, making it the leading brand of trastuzumab in China. Moreover, Henlius has proactively pursued overseas commercialisation of HANQUYOU, overseas revenue from product sales recorded RMB68.2 million approximately, up by 79.1% YoY. In April 2024, it received marketing approval from the U.S. Food and Drug Administration (FDA), making it a China-developed mAb biosimilar approved in China, the EU, and the U.S. In June 2024, HANQUYOU made its first delivery to Saudi Arabia，poised to be the first Chinese mAb to enter the Middle Eastern market. As of August 2024, the overseas commercialisation of HANQUYOU managed to include the markets of the U.S., Canada, the Philippines, Brazil, Uzbekistan and Turkmenistan, bringing more benefits to patients. HANSIZHUANG is the world’s first anti-PD-1 mAb approved for the first-line treatment of small cell lung cancer (SCLC), has been launched in China, Indonesia, Cambodia and Thailand. During the reporting period, HANSIZHUANG has recorded a sales revenue of RMB677.8 million, representing an increase of 21.8% YoY. Up to now, it has been approved for 4 indications, broadly covering high-incidence tumours including lung cancer and gastrointestinal cancer, benefiting over 7,5000 patients. Additionally, the 5th NDA of HANSIZHUANG for the first-line treatment of non-squamous non-small cell lung cancer (nsNSCLC) has been accepted by the National Medical Products Administration (NMPA), and expected to be approved in the second half of 2024. On the other hand, overseas sales revenue and licensing of HANSIZHUANG recorded RMB75.2 million approximately. Henlius continues to expand HANSIZHUANG’s global footprint, which now covers more than 70 countries and regions including the U.S., Europe, Southeast Asia and MENA, making it the first China anti-PD-1 mAb successfully approved for marketing in Southeast Asia. In the first quarter of 2024, Henlius has finished the first international shipment of HANSIZHUANG, opening a new chapter in benefiting patients worldwide with this product. HANSIZHUANG’s Marketing Authorisation Application (MAA) for ES-SCLC has been validated by the European Medicines Agency (EMA), which is expected to be approved in 2024. The company has also submitted marketing applications for HANSIZHUANG in Singapore and Malaysia to further promote the product in Southeast Asia. Moreover, Henlius steadily advances a head-to-head bridging trial in the United States to compare HANSIZHUANG to standard of care atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC, and plans to submit the Biologic License Application (BLA) of the product in the U.S. in early 2025. In the first half of 2024, Henlius achieved a number of milestones in business development. Regarding HLX78 (lasofoxifene), the company expanded its collaboration with Sermonix in all of Asia. Additionally, Henlius reached cooperation with Convalife to commercialise neratinib (trade name: HANNAIJIA), which is indicated for extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy, further enriching the company’s product pipeline for breast cancer treatment and creating synergy with HANQUYOU. Meanwhile, the company joined hands with international partners such as Accord, Eurofarma, KGbio and Organon to accelerate overseas commercialisation of its products. In the first half of 2024, HANLIKANG, the first biosimilar launched in China, has been approved to be marketed in Peru, which made it the company’s third self-developed and manufactured product breaking into global markets. Furthermore, the marketing application for HLX14 (denosumab biosimilar) has been accepted for review in European Union (EU) in May 2024, and expected to be approved in 2025. The company also plans to submit marketing applications for HLX14 in the U.S., and for HLX11 (pertuzumab biosimilar) in China and the U.S. in the second half of 2024. Synergistic Growth: Accelerating Innovation & Ensuring Manufacturing Meets International Quality Standards In the first half of 2024, Henlius hase been continuously advancing its differentiated R&D pipeline with the vision of offering high-quality and affordable innovation products, proactively exploring novel modalities and diverse disease areas. Guided by unmet clinical needs, the company has accelerated the clinical researches of a number of innovative products including HANSIZHUANG (serplulimab), HLX22 (anti-HER2 mAb), HLX42 (EGFR-targeting ADC) and HLX6018 (anti- GARP/TGF-β1 mAb). During the reporting period, the phase 3 international multicenter clinical study (ASTRUM-015) of serplulimab in combination with bevacizumab and chemotherapy indicated for the treatment of metastatic colorectal cancer (mCRC) has been permitted by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) and completed dosing of the first subject in China. Meanwhile, a phase 3 international multicenter clinical study of Henlius’ novel anti-HER2 mAb, HLX22, in combination with trastuzumab and chemotherapy for the treatment of HER2-positive advanced gastric cancer has been approved by the U.S. FDA. The latest results for innovative products such as HANSIZHUANG and HLX22 have been presented to global academic community, including Cancer Cell, Med, AACR, ASCO, ASCO GI, ESMO GI, and ENCALS, gaining wide recognition. Moreover, the company has completed the first patient dosing for clinical trials of HLX42, the potential first/best-in-class EGFR-targeting ADC, and of HLX6018, the company’s first novel product in chronic inflammatory diseases area. In addition, the company has received the IND approval for the clinical trial of novel anti-TIGIT fc fusion protein HLX53 in combination with HANSIZHUANG plus HANBEITAI for the first-line treatment of locally advanced or metastatic hepatocellular carcinoma (HCC) from the NMPA, and has completed the first patient dosing for a phase 2 clinical trial. While boosting innovation, Henlius is steadily consolidating international high quality manufacturing capability to accelerate its global commercialisation layout, translating the R&D efforts into social impact and commercial results. The company currently has three manufacturing facilities: Shanghai Xuhui Facility, Songjiang First Plant and Songjiang Second Plant. Regarding Songjiang Second Plant, the company has completed construction and validation of drug substance (DS), drug product (DP) and prefilled syringes system (PFS) line of the two major manufacturing buildings in the Phase I & II project, and main structural framework was topped out in the Phase III project. Currently, the commercial capacity of the company is 48,000 litres, enabling stable supply to markets beyond China, including Europe, Southeast Asia, Latin America and Middle East. Additionally, the company has always been upholding the highest quality standards, allowing its products to go global. As of now, Henlius’ commercial production facilities and supporting quality management system have also passed nearly one hundred on-site inspections and audits conducted by the NMPA, the EMA, the FDA, the EU Qualified Person (QP), as well as Henlius’ international business partners, and have been GMP-certificated by China, the EU and U.S. regulatory agencies. The company also adopted a series of lean operation projects, optimised production processes, utilized digital technology to empower supply chain, inventory and quality management, putting "affordable innovation, trustworthy quality" into practice. Focusing on patients unmet clinical needs, Henlius will further strengthen its commercialisation capabilities as a biopharma, improve the operation efficiency of its integrated biopharmaceutical platform, and expand its global presence, enabling high-quality innovative outcomes to benefit more patients worldwide. 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, 6 products have been launched in China, 3 have been approved for marketing in overseas markets, 24 indications are approved worldwide, and 3 marketing applications have been accepted for review in China and the EU, respectively. 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 centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP. Henlius has pro-actively built a diversified and high-quality product pipeline covering over 50 molecules 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: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab), HANBEITAI (bevacizumab) and HANNAIJIA (neratinib), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. What’s more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets. 联系方式媒体：PR@Henlius.com 投资者：IR@Henlius.com 喜欢本文内容点击下方按钮·分享 ·收藏 ·点赞 ·在看

财报突破性疗法上市批准

2024-08-08

·复宏汉霖

产品速递 | 双免疫联合抗血管靶向疗法，HLX53联合H药与汉贝泰®一线治疗肝细胞癌的II期临床试验完成首例患者给药

2024年8月8日，复宏汉霖（2696.HK）宣布，公司自主开发的创新型抗TIGIT Fc融合蛋白HLX53联合H药汉斯状®（斯鲁利单抗，HLX10）及汉贝泰®（贝伐珠单抗，HLX04）在局部晚期或转移性肝细胞癌患者中开展的II期临床试验（NCT06349980）完成首例患者给药。肝癌是全球范围内常见的恶性肿瘤。据GLOBOCAN统计，2022年全球肝癌发病数和死亡数分别为87万及76万例 [1]。在中国，原发性肝癌是第五大最常见的癌症，以及第二大致死癌症。2022年中国新发肝癌病例约37万例，肝癌死亡病例32万例。其中，肝细胞癌是最常见的原发性肝癌类型，约占总病例数的75-85% [2]。因原发性肝癌起病隐匿，早期无症状或症状不明显，进展迅速，确诊时大多数患者已经达到局部晚期或发生远处转移，治疗困难，预后很差，五年生存率仅约18% [3]。对晚期肝癌患者来说，目前一线治疗以靶向治疗和免疫治疗为主，免疫抑制剂及抗血管生成药物的联合治疗显示出显著的临床抗肿瘤活性和生存获益 [2]，但仍有较大比例的患者并不能从中获益，导致肿瘤复发或进展，尚存在迫切的临床需求以扩大免疫治疗的受益人群，并提高免疫治疗的疗效。含免疫球蛋白和ITIM结构域的T细胞免疫受体（T cell immunoglobulin and ITIM domain, TIGIT）是近年来肿瘤免疫治疗中最有前景和潜力的靶点之一。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，其重要配体为主要表达于APC（抗原提呈细胞）或肿瘤细胞表面的CD155（脊髓灰质炎病毒受体，PVR）[4]。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。多项研究数据显示，TIGIT抑制剂有望治疗多种晚期癌症，包括肺癌、胃癌、黑色素瘤和多发性骨髓瘤等多种实体瘤和淋巴瘤。且已有临床前研究表明，TIGIT靶点可能与 PD-1 通路产生协同效应，同时阻断TIGIT和PD-1/PD-L1信号通路优于单独阻断任一通路，可增强抗肿瘤活性[5]。 HLX53是复宏汉霖自主研发的创新型抗TIGIT的Fc融合蛋白，由重链抗体的可变区（VHH）和野生型 IgG1的Fc端组成。临床前研究结果表明，HLX53具有优异的肿瘤抑制效果且安全性良好。公司亦于2022年启动了一项I期临床研究，以评估HLX53在晚期/转移性实体瘤患者中的安全性、耐受性、药代动力学特征及初步疗效。鉴于抗PD-1/PD -L1单抗等免疫抑制剂及抗血管生成药物在晚期肝细胞癌患者中取得的良好疗效，及TIGIT与PD-1/PD-L1信号通路的协同效应，复宏汉霖旨在通过开展此项研究，进一步探索抗PD-1单抗与TIGIT抑制剂的双免疫治疗与抗血管靶向疗法的组合，以期为晚期肝细胞癌患者带来更高的临床获益。复宏汉霖从临床需求出发，目前在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。同时，公司充分运用自有管线覆盖肿瘤特异性靶点、抗血管生成靶点和肿瘤免疫靶点等多个类别的特点，助力H药与自有单抗产品、化疗等治疗手段开展联合治疗，有助于充分挖掘免疫疗法的治疗潜力，为全球患者带去高品质、可负担的创新治疗方案。【参考文献】 [1] Globocan 2022 (version 1.1) - 08.02.2024；https://gco.iarc.fr/today/en/dataviz/bars-compare-populations?mode=cancer&group_populations=1&cancers=11&populations=900&sort_by=value1&types=0_1&key=total [2]原发性肝癌诊疗指南（2024年版） [3] Asafo-Agyei KO, Samant H. Hepatocellular Carcinoma. 2023 Jun 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32644603. [4] Chauvin, Joe-Marc, and Hassane M Zarour. “TIGIT in cancer immunotherapy.” Journal for immunotherapy of cancer vol. 8,2 (2020): e000957. doi:10.1136/jitc-2020-000957. [5] Chu, Xianjing et al. “Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials.” Molecular cancer vol. 22,1 93. 8 Jun. 2023, doi:10.1186/s12943-023-01800-3. 关于NCT06349980 本研究为一项随机、双盲、多中心的II期临床研究，旨在评估HLX53联合汉斯状®及汉贝泰®对比安慰剂联合汉斯状®及汉贝泰®在未经治疗的局部晚期或转移性肝细胞癌患者中的有效性、安全性和耐受性。研究分为两个部分：A部分为安全导入期，将采用“3+3”剂量递增设计，合格的受试者将接受每三周一次静脉输注不同剂量HLX53（1000 mg或2000 mg）联合汉斯状®（300 mg）及汉贝泰®（15 mg/kg）的治疗；B部分为初步疗效探索期，合格的受试者将按照1:1:1的比例，随机分配接受每三周一次静脉输注HLX53（1000 mg）、HLX53（2000 mg）或安慰剂分别联合汉斯状®（300 mg）及汉贝泰®（15 mg/kg）的治疗。A部分的主要终点为安全性和耐受性，评估每个剂量组中发生剂量限制毒性（DLT）事件的患者比例。B部分的主要终点为由独立影像评估委员会根据RECIST v1.1评估的客观缓解率和无进展生存期。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，在国际获批上市3款产品，23项适应症获批，3个上市申请分别获中国药监局和欧盟EMA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，公司商业化生产基地已相继获得中国、欧盟和美国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50多个分子，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）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：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、鳞状非小细胞肺癌、广泛期小细胞肺癌和食管鳞状细胞癌，并成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。公司亦同步就16个产品在全球范围内开展30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 Patient Dosed of Phase 2 Clinical Trial of Novel Anti-TIGIT Fc Fusion Protein in Combination with Serplulimab Plus HANBEITAI for the First-line Treatment of Locally Advanced or Metastatic Hepatocellular Carcinoma Patients Shanghai, China, August 8, 2024 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient has been dosed in a phase 2 clinical trial (NCT06349980) of HLX53, an anti-TIGIT Fc fusion protein, in combination with HANSIZHUANG (serplulimab, HLX10) and HANBEITAI (bevacizumab, HLX04) for the first-line treatment of locally advanced or metastatic hepatocellular carcinoma (HCC). Liver cancer is one of the most prevalent malignancy in the world. According to GLOBALCAN 2022, there are about 870,000 new cases diagnosed and 760,000 deaths for the tumour in the globe[1]. Meanwhile, primary liver cancer (PLC) is the fifth most common cause and the second mortality cancer in China, with about 370,000 new cases and 320,000 deaths in 2022. From which, hepatocellular carcinoma (HCC) is the predominant pathological type of PLC, which accounts for between 75% and 85% of liver cancer cases[2]. Due to its insidious onset, lack of symptom in its early stage, and quick progression, PLC usually has been in its locally advanced stage or develops distant metastasis when it is diagnosed. As a result, the management becomes extremely difficult and the prognosis usually is poor. The 5-year survival rate of PLC is only about 18%[3]. For patients with advanced liver cancer, the first-line treatment is based on targeted therapy and immunotherapy. And the standard therapy (combination therapies of immune inhibitor plus anti-angiogenic treatment) have shown significant clinical anti-tumour efficacy and survival benefit[2]. However, some patients failed to benefit from the standard therapy and suffered from recurrence or progression of the disease. Thers is still an urgent clinical need to further expand the benefit population with advanced liver cancer and improve the efficacy of immunotherapy. T-cell immunoglobulin and ITIM domains (TIGIT) has emerged as popular inhibitory checkpoint receptor, which is mainly expressed on natural killer (NK) cells, activated CD8+ T and CD4+ T cells, and T regulatory cells. TIGIT binds to the ligand CD155 (poliovirus receptor, PVR)[4], mainly expressed on antigen-presenting cells (APC) or the surface of tumour cells, to down-regulate T cell and NK cell functions. As an immune checkpoint protein, TIGIT can inhibit innate and adaptive responses in various mechanisms of action and act as “brakes” like PD-1/PD-L1 does to stop T cells from attacking tumours. Studies have shown that TIGIT inhibitor are effective against lung cancer, gastric cancer, melanoma, multiple myeloma, etc. Moreover, TIGIT has shown a synergistic effect with the PD-1 pathway in preclinical studies, indicating that simultaneous blocking of TIGIT and PD-1/PD-L1 signaling pathways is superior to blocking either pathway alone, which can enhance anti-tumour activity[5]. HLX53 is an anti-TIGIT Fc fusion protein independently developed by Henlius, consisting of variable domain of heavy chain of heavy-chain antibody (VHH) and wildtype IgG1 Fc. Pre-clinical studies have demonstrated that HLX53 exhibits excellent tumour inhibition with good safety. In addition, Henlius has initiated a phase 1 study to evaluate the safety, tolerability, pharmacokinetics characteristics and preliminary efficacy of HLX53 in patients with advanced/metastatic solid tumors. Considering the good efficacy of immune checkpoint inhibitor such as anti-PD-1/PD-L1 antibody plus anti-angiogenic drug in the first-line treatment of patients with advanced HCC, as well as the synergistic effect of TIGIT and PD-1/PD-L1 signaling pathway, Henlius intends to further combine TIGIT inhibitor based on the standard therapy in order to bring greater clinical benefits to patients with advanced HCC. Underpinned by the patient-centric strategy, Henlius has achieved an overall layout of the immune checkpoint products of PD-1/L1, CTLA-4, LAG-3, etc., proactively exploring immuno-oncology combination therapy. Meanwhile, Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company such as tumour-specific target, angiogenesis target, immunotherapeutic target, etc. and chemotherapy drugs to conduct immune combination therapies in a wide variety of indications, committing to bringing affordable and high-quality innovative biologics to patients around the world. About NCT05483530 This randomised, double-blind, multicentre phase 2 clinical study aims to evaluate the efficacy, safety, and tolerability of HLX53 in combination with HANSIZHUANG and HANBEITAI versus placebo in combination with HANSIZHUANG and HANBEITAI in previously untreated patients with locally advanced or metastatic hepatocellular carcinoma. The study consists of two parts. Part A is the safety run-in stage, which follows a “3+3” dose-escalation design. Eligible patients will be given different doses of HLX53 (1000 mg or 2000 mg) in combination with HANSIZHUANG (300 mg) and HANBEITAI (15 mg/kg) intravenously, every three weeks. Part B is the preliminary efficacy exploration stage. Eligible patients will be randomly assigned (1:1:1) to receive intravenous HLX53 (1000 mg), HLX53 (2000 mg), or placebo in combination with HANSIZHUANG (300 mg) and HANBEITAI (15 mg/kg), every three weeks. The primary endpoints of Part A are safety and tolerance， evaluating the proportion of patients with a dose-limiting toxicity (DLT) event in each group. The primary endpoints of Part B are objective response rate and progression-free survival assessed by independent radiological review committee per RECIST v1.1. 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, 3 have been approved for marketing in overseas markets, 23 indications are approved worldwide, and 3 marketing applications have been accepted for review in China and the EU, respectively. 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 centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP. Henlius has pro-actively built a diversified and high-quality product pipeline covering over 50 molecules 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: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC) and extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. What’s more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets. 联系方式媒体：PR@Henlius.com 投资者：IR@Henlius.com 喜欢本文内容点击下方按钮·分享 ·收藏 ·点赞 ·在看

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