全球研发 | 创新联合疗法用于肾小球肾炎，HLX79联合汉利康II期临床完成首例...

2025年8月6日，复宏汉霖（2696.HK）宣布，潜在同类首创（first-in-class）人唾液酸酶融合蛋白HLX79（E-602）联合汉利康（利妥昔单抗）治疗活动期肾小球肾炎的II期临床试验（HLX01HLX79-GN201）于中国完成首例患者给药。汉利康现已在中国获批用于治疗非霍奇金淋巴瘤（NHL）、慢性淋巴细胞白血病（CLL）、类风湿性关节炎（RA），是目前国内唯一获批用于自身免疫疾病治疗的利妥昔单抗。此外，汉利康亦在拉美多国获批用于治疗血管炎肉芽肿（GPA）、显微镜下多血管炎（MPA）和寻常型天疱疮（PV）等自身免疫疾病。

终末期肾病（ESRD）是慢性肾脏病（CKD）的终末阶段，这一阶段患者肾功能几乎完全丧失，需长期依靠肾脏替代治疗维持生命，具有疾病严重程度高、多并发症高发、治疗花费负担重等特点^[1]。中国ESRD患者数量位居全球首位，占比接近30%，折合现有患者人数达350万^[2]。而中国终末期肾病的主要病因为肾小球肾炎，包括原发性肾小球肾炎和继发性肾小球肾炎。原发性肾小球肾炎包括膜性肾病（MN）、局灶节段性肾小球硬化（FSGS）等。继发性肾小球肾炎包括狼疮肾炎（LN）、抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）肾损害等^[1]。

近年来，以利妥昔单抗（抗CD20单抗）等靶向抗体为代表的B细胞清除疗法，已在全球多个市场获批并被中华医学会肾脏病学专家共识推荐用于治疗肾小球肾炎^[1]。然而，许多患者对这类药物的治疗反应并不理想。糖免疫提供了一种治疗自身免疫疾病的新方法。该策略通过酶解唾液酸糖苷，打破致病性免疫细胞的“保护屏障”， 从而增强其清除效果，帮助恢复机体免疫平衡。

HLX79是基于Palleon的EAGLE糖编辑平台开发的潜在“同类首创”的人唾液酸酶融合蛋白。HLX79 通过酶解唾液酸糖苷，从而增强对两类在自身免疫疾病中高度致病的免疫细胞的清除：一是驱动炎症的自身反应性记忆B细胞，二是促进纤维化和器官损伤的M2型巨噬细胞。

临床前研究表明，与利妥昔单抗单药相比，HLX79与利妥昔单抗联用的疗效显著提升，且不会引发CAR-T疗法或T细胞结合剂相关的细胞因子释放综合征（CRS）或免疫效应细胞相关神经毒性综合征（ICANS）。在此前的临床试验中，HLX79展现出良好的安全性特征，无剂量限制性毒性。HLX79联用利妥昔单抗有望为活动期肾小球肾炎患者带来临床获益。

未来，复宏汉霖还将持续立足于未满足的临床需求，充分发挥公司在抗体药物领域的一体化平台优势，不断拓展疾病领域和新分子类型，为全球患者带来更多高质量、可负担的创新治疗方案。

参考文献

[1] 中华医学会肾脏病学分会专家组. 利妥昔单抗在肾小球肾炎中应用的专家共识[J]. 中华肾脏病杂志, 2022, 38(2):151-160. [2] IQVIA《中国终末期肾病白皮书》

关于HLX01HLX79-GN201

本研究为一项双盲、随机对照、多中心的2期临床试验，旨在评估HLX79联合汉利康对比安慰剂在活动期肾小球肾炎（狼疮肾炎（LN）和膜性肾病（MN））患者中的有效性、安全性和耐受性。研究分为两个阶段，第一阶段为剂量递增期，按照剂量递增设计原则，合格的受试者将每周一次接受HLX79（10 mg/kg、20 mg/kg或30 mg/kg）联合汉利康或汉利康安慰剂（375 mg/m2）给药，主要研究目的为评价HLX79联合汉利康对比安慰剂联合汉利康治疗活动期肾小球肾炎的安全性和耐受性；第二阶段为初步疗效探索期，筛选合格的受试者将按照2:2:1:1的比例，每周一次接受HLX79（高剂量/低剂量）联合汉利康（375 mg/m2）、HLX79安慰剂联合汉利康、或HLX79安慰剂联合汉利康安慰剂给药，主要研究目的为在标准治疗基础上，评价HLX79联合汉利康、安慰剂联合汉利康以及安慰剂治疗活动期肾小球肾炎的临床疗效，次要研究目的为评估其他临床疗效、安全性、耐受性、药代动力学（PK）特征和免疫原性，探索性目的为评估潜在生物标志物的动态变化。

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，4款产品在国际获批上市，5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，涵盖约50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）、全球首个获批一线治疗小细胞肺癌的抗PD-1单抗汉斯状（斯鲁利单抗，欧洲商品名：Hetronifly）以及汉奈佳（奈拉替尼）。公司亦同步就19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 Doses First Patient in Phase 2 Trial of HLX79 and HANLIKANG for Glomerulonephritis

Shanghai, China, August 6, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first patient has been dosed in a phase 2 clinical trial (HLX01HLX79-GN201) for the potential first-in-class human sialidase enzyme therapeutic, HLX79 (E-602), in combination with Henlius’ self-developed HANLIKANG (rituximab) in patients with active glomerulonephritis.

End stage renal disease (ESRD), the last stage of chronic kidney disease (CKD), is characterised by near-total loss of kidney function, resulting in the need for renal replacement therapy. Patients face high disease severity, complications, and substantial economic burden due to the costs of treatment^[1]. China accounts for nearly 30% of global ESRD cases, with approximately 3.5 million patients^[2]. Glomerulonephritis can be classified into primary forms (e.g., membranous nephropathy [MN], focal segmental glomerulosclerosis [FSGS]) and secondary forms (e.g., lupus nephritis [LN], anti-neutrophilic cytoplasmic antibodies [ANCA]-associated vasculitis [AAV]), representing the leading cause of ESRD in China^[1].

HANLIKANG, approved in China for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis, remains the only rituximab approved for an autoimmune indication in China. Depleting B cells with targeted antibodies such as rituximab (anti-CD20 mAb), has been approved in multiple markets for the treatment of glomerulonephritis. However, many patients have inadequate response to these drugs. Glyco-immunology provides a new approach to treating autoimmunity by degrading immune-inhibitory sialoglycan sugar molecules that help pathogenic immune cells evade immune clearance to enhance their depletion and restore immune balance.

HLX79 is a potential first-in-class human sialidase enzyme therapeutic developed based on Palleon’s EAGLE glycan editing platform and licensed in China by Henlius from Palleon. HLX79 degrades sialic acid, enhancing the clearance of two highly pathogenic immune cell populations in autoimmunity: autoreactive memory B cells, which drive inflammation, and M2-like macrophages, which promote fibrosis and organ damage. Preclinical studies of HLX79 in combination with rituximab demonstrate improved outcomes versus rituximab alone without the risk of cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) associated with CAR T and T cell engagers. HLX79 has demonstrated a favourable safety profile with no dose-limiting toxicities in human clinical trials. It is expected that the combination of HANLIKANG and HLX79 will benefit patients with active glomerulonephritis.

Moving forward, Henlius will continue to focus on unmet clinical needs by fully leveraging its integrated platform advantages in antibody-based drugs, expanding disease areas, accelerating the development of differentiated molecules, and bringing more high-quality, affordable innovative therapies to patients worldwide.

About HLX01HLX79-GN201

This study is a double-blind, randomized, controlled, multicenter, Phase 2 study to evaluate the efficacy, safety, and tolerability of HLX79 in combination with HANLIKANG compared with placebo in patients with active glomerulonephritis (lupus nephritis (LN) and membranous nephropathy (MN)). The study includes two parts. Part 1 of the study is the dose escalation period. Eligible subjects will receive HLX79 (10 mg/kg, 20 mg/kg, or 30 mg/kg) or placebo combined with HANLIKANG (375 mg/m²) once a week. The primary objective is to evaluate the safety and tolerability of HLX79 in combination with HANLIKANG, and placebo in combination with HANLIKANG for glomerulonephritis. Part 2 of the study is the preliminary efficacy exploration period. Eligible subjects will receive HLX79 (high dose/low dose) combined with HANLIKANG (375 mg/m²), HLX79 placebo combined with HANLIKANG, or HLX79 placebo combined with HANLIKANG placebo once a  week at a ratio of 2:2:1:1. The primary objective of part 2 is to evaluate the clinical efficacy of HLX79 in combination with HANLIKANG, placebo in combination with HANLIKANG, as well as placebo alone, in subjects with glomerulonephritis on the basis of standard treatment. The secondary objectives include other clinical efficacy, safety, tolerability, pharmacokinetic (PK) characteristics, and immunogenicity. The exploratory objective is to evaluate the dynamic changes of potential biomarkers.

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, 4 have been approved for marketing in overseas markets, and 5 marketing applications have been accepted for review in China, the U.S. 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 about 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. To date, the company's launched products include 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), HANSIZHUANG (serplulimab, trade name: Hetronifly in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, and HANNAIJIA (neratinib). What’s more, Henlius has conducted over 30 clinical studies for 19 products, expanding its presence in major markets as well as emerging markets.

(复星医药)