聚焦自免疾病，HLX79联合汉利康II期临床在中国获批开展

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。然而，许多患者对这类药物的治疗反应并不理想。记忆B细胞是一类与自身免疫疾病进展相关的致病性B细胞亚群，常与抗体介导的B细胞清除疗法的耐药相关。通过增强记忆B细胞的消耗，糖免疫提供了一种治疗自身免疫疾病的新方法。HLX79能够酶解唾液酸糖苷，后者是一种表达于细胞表面的免疫抑制性唾液酸聚糖，其功能是保护致病性记忆B细胞免受B细胞靶向抗体的消耗。

HLX79是基于Palleon的EAGLE糖编辑平台开发的同类首创的人唾液酸酶融合蛋白。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）和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。

Henlius Announces China’s NMPA Approval of Phase 2 Clinical Trial for HLX79 Plus HANLIKANG in Active Glomerulonephritis

Shanghai, China, March 25, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the National Medical Products Administration (NMPA) has approved the investigational new drug (IND) application for a phase 2 clinical trial 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. HANLIKANG, approved in 2022 for rheumatoid arthritis, remains the only rituximab approved for an autoimmune indication in China.

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].

Depleting B cells with targeted antibodies such as rituximab (anti-CD20 mAb), has been approved in multiple markets and is recognised by Chinese nephrology expert consensus for the treatment of glomerulonephritis. However, many patients have inadequate response to these drugs. Glyco-immunology provides a new approach to treating autoimmunity by enhancing depletion of activated memory B cells, the pathogenic subset of B cells associated with disease progression and often resistant to antibody-mediated depletion. HLX79 enzymatically degrades sialoglycans—immunosuppressive cell surface sugars that protect pathogenic memory B cells from depletion by B cell-targeted antibodies.

HLX79 is a first-in-class human sialidase enzyme therapeutic developed from Palleon’s EAGLE glycan editing platform. Preclinical studies of HLX79 in combination with rituximab demonstrate improved outcomes versus rituximab alone without the risk of cytokine release syndrome (CRS) and 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.

Looking forward, Henlius will continue to promote the layout of our innovative portfolio by focusing on antibody technology, bringing more high-quality and affordable therapeutics to patients worldwide.

References

[1] Chinese Society of Nephrology. Expert consensus on the use of rituximab in glomerulonephritis[J]. Chinese Journal of Nephrology, 2022, 38(2): 151-160. DOI: 10.3760/cma.j.cn441217-20210615-00023.

[2] IQVIA’s White Paper on End-Stage Renal Disease in China, 2023

媒体：PR@Henlius.com

投资者：IR@Henlius.com