产品速递 | 探索ADC免疫联合疗法，复宏汉霖 PD-L1 ADC HLX43联合H药临床试验申请获NMPA批准

近年来，以抗PD-1/L1抗体为代表的免疫检查点抑制剂促进了肿瘤免疫治疗（IO）的高速发展，成为肿瘤患者的主要治疗手段之一。然而，部分患者对该疗法无响应，或者出现耐药^[1]。因此，免疫疗法与其他治疗方式联合，有望成为免疫治疗耐药后、免疫治疗冷肿瘤患者的治疗策略之一，极具开发潜力。而近年来多种新分子类型的涌现，为免疫联合治疗提供了新的选择。其中，ADC是当下肿瘤治疗中疗效最突出的新型疗法，但其单药治疗也存在耐药等问题的限制。ADC与免疫治疗的组合方案（IO+ ADC），不仅有望发挥协同增效的抗肿瘤作用，提高免疫治疗的疗效和缓解率，潜在还能够逆转耐药出现，突破现有药物的治疗瓶颈^[2]。

H药 汉斯状^®（通用名：斯鲁利单抗注射液）是全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，已在中国和多个东南亚国家获批上市，惠及患者逾9万人。聚焦肺癌和消化道肿瘤等高发大瘤种，复宏汉霖积极推进斯鲁利单抗与其他自有产品的协同以及与创新疗法的联合，目前汉斯状已在中国获批鳞状非小细胞肺癌（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）、食管鳞状细胞癌（ESCC）和非鳞状非小细胞肺癌（nsNSCLC），其一线治疗广泛期小细胞肺癌（ES-SCLC）的上市申请也已获得欧盟EMA受理，有望于2025年获批上市。同时，公司在全球同步开展10余项肿瘤免疫联合疗法临床试验，于中国、美国、土耳其、波兰、格鲁吉亚等国家和地区累计入组超4800人。

HLX43是复宏汉霖首批进入临床阶段的ADC产品之一，已于2023年11月在中国完成首例受试者给药，成为国内首个进入临床阶段的靶向PD-L1的ADC产品。HLX43兼具抗体分子的高度靶向性和细胞毒素的强大杀伤力，可通过与肿瘤细胞表面PD-L1 抗原特异性结合，经内吞后释放小分子毒素，从而发挥抗肿瘤作用。目前，HLX43已在临床前药理学研究、药代动力学研究及安全性评价中展现出抗肿瘤活性，且具有良好的安全性。该研究数据于2023欧洲肿瘤内科学会（ESMO）大会以壁报形式进行展示。立足于公司在抗体药物领域的一体化平台优势，复宏汉霖加速拓展抗体偶联药物（ADC）及多样化的靶向偶联药物（AXC/XXC）的开发，并积极探索ADC与免疫治疗药物的联用方案，前瞻性布局IO+ADC治疗领域，以进一步提高患者的临床获益，解决未满足的临床需求。

未来，复宏汉霖将继续发挥公司在抗体药物和抗体偶联药物领域的一体化平台优势，以创新为引擎，加速推动更多前沿治疗策略的研发进程，为全球患者带来更多高质量、可负担的创新治疗方案。

Henlius Receives the NMPA IND Approval for Its PD-L1-Targeting ADC HLX43 in Combination with Novel Anti-PD-1 mAb Serplulimab

Shanghai, China, January 10, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug (IND) application for a phase 1b/2 clinical trial of HLX43, the antibody-drug conjugate (ADC) that developed by the company based on the collaboration with MediLink Therapeutics, in combination with the company's independently developed innovative anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab injection), has been approved by the China National Medical Products Administration (NMPA), for the treatment of advanced/metastatic solid tumours. In December 2024, a phase 1b/2 clinical trial of HLX43 has been approved by the NMPA for monotherapy or combination therapy to treat patients with advanced/metastatic solid tumours. At present, no PD-L1 targeting ADC has been approved for marketing globally.

Immune checkpoint inhibitors represented by PD-1/PD-L1 monoclonal antibodies have emerged in recent years and revolutionised all lines of immuno-oncology (IO) therapies for tumour patients. However, there are still many patients do not respond to or develop resistance to PD-1/PD-L1-targeted therapies^[1]. Therefore, immunotherapy in combination with other treatments is expected to be a promising therapeutic strategy for patients who develop drug resistance or with “cold” tumours. Meanwhile, the emergence of varied new modalities has provided new options for immunotherapies to combined with. From which, ADC is a novel targeting therapy with the most prominent anti-tumour efficacy, while the utility of ADC as a monotherapy is also limited by issues such as drug resistance. Therefore, the combination of ADCs and immunotherapies may exert synergistic anti-tumour activities that ultimately leading to potent efficacy and durable responses of the IO therapeutics, and potentially reversing the emergence of resistance, further providing more effective treatment options to fulfill the unmet clinical needs^[2]. 

HANSIZHUANG (serplulimab), Henlius’ first self-developed innovative anti-PD-1 mAb, is the world’s first anti-PD-1 mAb for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). It has been approved in China and several Southeast Asian countries, benefiting over 90,000 patients. Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. Up to date, HANSIZHUANG has been approved by the NMPA for the treatment of squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), esophageal squamous cell carcinoma (ESCC) and non-squamous non-small cell lung cancer (nsNSCLC). Furthermore，the marketing applications of the first-line treatment for ES-SCLC is under review by the European Medicines Agency (EMA), which is expected to be approved in 2025. Meanwhile, the company has initiated more than 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications with more than 4,800 subjects enrolled in China, the U.S., Turkey, Poland, Georgia and other countries and regions.

HLX43 is one of the first ADC candidates of Henlius to enter into clinical development. In November 2023, the company has dosed the first subject for a phase 1 clinical trial of HLX43, making it the first PD-L1-targeting ADC in China to enter a clinical trial. Combining the selectivity of targeted monoclonal antibodies with the highly potent cytotoxic agent, HLX43 could exert anti-tumour effects through specific binding to the PD-L1 expressed on the surface of tumour cells and release cytotoxic payloads after internalisation by the cancer cells. Up to date, HLX43 has exhibited good anti-tumour effects and a favorable safety profile in nonclinical pharmacology, pharmacokinetic studies and safety evaluation. The results of the studies were published as poster presentation at the 2023 European Society of Medical Oncology (ESMO) Congress. Leveraging the company’s competitive edge of an integrated antibody drug R&D platform, Henlius is accelerating the development of ADCs and diversified drug conjugates, and actively exploring combination therapies involving ADCs and immunotherapies to encourage progress in the next wave innovation of “IO+ADC”.

Looking forward, Henlius will further take efforts to promote the layout of our innovative portfolio by focusing on antibody and novel conjugating technologies, bringing more high-quality and affordable therapeutics for patients worldwide.