PD-L1 ADC HLX43关键数据更新发布，全球临床价值持续验证

HLX43是一款潜在同类最优及疾病领域最优的广谱抗肿瘤ADC，兼具免疫检查点阻断与载荷细胞毒性的双重作用机制。临床前研究显示，HLX43在PD-1/PD-L1单抗耐药的非小细胞肺癌、宫颈癌、食管鳞癌等多个瘤种中展现出治疗潜力，且耐受性良好。其I期临床数据于2025美国临床肿瘤学会（ASCO）年会及2025 世界肺癌大会（WCLC）上先后发布，在NSCLC等实体瘤中展现出“高效、低毒”的显著疗效，尤其在NSCLC的治疗上，HLX43展现了全人群覆盖的潜力，对于鳞状/非鳞状NSCLC，有无EGFR突变、有无脑转移、PD-L1阳性/阴性的NSCLC患者人群都具有疗效，不依赖生物标志物筛选。

基于前期剂量探索结果，我们前瞻性确定了2.0 mg/kg 或 2.5 mg/kg 作为HLX43在NSCLC研究中的II/III期推荐剂量（RP2/3D）。此次发布的更新NSCLC人群研究数据，即聚焦于呈现HLX43在NSCLC研究领域的关键数据。为此我们整合了自HLX43-FIH101及HLX43-NSCLC201两项研究中，分别接受这两个剂量治疗的NSCLC患者数据（合计174例），以系统性评估RP2/3D下的疗效和安全性，为后续关键临床试验的决策提供核心依据。

其中，HLX43-FIH101是一项在中国开展的开放标签、首次人体I期研究，旨在评估HLX43在晚期/转移性实体瘤患者中的安全性、药代动力学特征和初步疗效，研究分别探索了0.5-4.0 mg/kg剂量下患者的最大耐受剂量（MTD），及评估2.0-3.0 mg/kg剂量对标准治疗无效的晚期或转移性非小细胞肺癌（NSCLC）患者的疗效，以确定II期推荐剂量（RP2D）。HLX43-NSCLC201是一项评估HLX43在晚期NSCLC患者中疗效和安全性的开放、国际多中心II期临床试验，入组接受至少一线标准治疗失败的NSCLC患者，研究分剂量探索（A阶段）和剂量扩展（B阶段）两个阶段，主要研究终点是由盲态独立中心审查委员会根据RECIST v1.1标准评估的客观缓解率（ORR）。

关键疗效数据更新（含亚组数据分析）

截至2025年10月22日，研究共纳入174例晚期NSCLC患者，其中接受2.0 mg/kg HLX43静脉注射治疗的患者为89例，接受2.5 mg/kg 治疗的患者为85例。全部患者（100%）接受过铂类药物治疗，约80%和逾30%的患者分别接受过免疫治疗和靶向治疗，部分患者接受过多西他赛治疗，均为后线经治人群。

• 总人群疗效显著：经研究者评估，在鳞状非小细胞肺癌患者（2mg/kg，n=33）中，HLX43的客观缓解率（ORR）达33.3%，疾病控制率（DCR）为75.8%；在非鳞癌患者（2.5mg/kg，n=35,包括EGFR 野生型及EGFR突变）中，疗效更为突出，ORR提升至48.6%，DCR高达94.3%

• 多西他赛失败人群疗效突出：曾接受过多西他赛治疗的三线及后线鳞状NSCLC患者（2mg/kg，n=13）中，ORR达38.5%，DCR为84.6%，提示HLX43在多西他赛治疗失败的肺鳞癌人群中的重要潜力

• 非鳞状NSCLC治疗优势：在非鳞状NSCLC患者中（2.5mg/kg，n=35），ORR达48.6%，DCR为94.3%。值得关注的是，EGFR野生型非鳞状NSCLC患者（n=19）的ORR达47.4%，DCR达94.7%。EGFR突变的非鳞状NSCLC患者（n=16）中，ORR达50.0%，DCR达93.8%。彰显了HLX43在非鳞状NSCLC患者人群中更为显著的疗效优势

• 脑转移患者有效：在晚期的脑转移NSCLC患者（n=10）中，HLX43仍带来了显著的治疗获益，ORR为30.0%，DCR达90.0%

• 疗效不受PD-L1表达限制：在PD-L1阴性（TPS＜1%，n=43）患者群体中，HLX43展现了差异化的治疗潜力，ORR和DCR分别达到39.5%和86.0%，提示HLX43疗效不受PD-L1表达限制，有望覆盖更广泛的患者群体

安全性数据更新

• 安全性方面，最常见的≥3级治疗相关不良事件（TRAEs）包括淋巴细胞计数减少（9.8%）、贫血（8.6%）、中性粒细胞计数减少（6.3%），血小板计数减少仅1.7%。HLX43血液学毒性较低，延续了良好的安全性，支持未来扩展至一线疗法及联合治疗方案

• 其中，17例（9.8%）患者报告了免疫相关不良事件（irAE），5例（2.9%）患者出现免疫相关性肺病，目前均在恢复中。

• 同时，在发生免疫相关性肺病的患者人群中观察到显著治疗获益，包括40.0%的经确认客观缓解率（cORR）及100%的肿瘤缩小率，提示HLX43可能“双管齐下”，其疗效经由小分子毒素以及免疫机制介导。

HLX43优异的临床疗效和安全性特征，源自其精准的分子设计和多重创新机制。不同于市面上众多针对驱动基因突变的ADC，HLX43选择了PD-L1这一泛瘤种靶点，不依赖生物标志物的筛选，真正具备广谱ADC的开发潜力。HLX43的抗体骨架采用复宏汉霖自主研发的HLX20，具有抗原的高结合能力及肿瘤细胞的内吞效率，连接子—毒素引进自具有技术优势的宜联TMALIN^®平台，可裂解型连接子不仅通过内吞途径胞内释放毒素，还能够在肿瘤微环境中激活释放毒素，实现毒素于“胞内”和“胞外”的同时释放，基于此，HLX43兼具了ADC靶向杀伤与PD-L1/PD-1免疫检查点抑制剂（IO）的双重作用机制，使其成为一款具备双优潜力的ADC候选分子。

HLX43于2023年相继获得中国药品监督管理局（NMPA）、美国食品药品监督管理局（FDA）的临床试验许可。目前，公司正全力推进HLX43临床开发进程，在全球入组超过400例患者，其中NSCLC患者超过170例，并在中国、美国、日本等多国顺利推进患者入组。尤其在NSCLC适应症上，一项国际多中心II期临床研究正在中、美、日、澳等国家同步开展。随着这一适应症的后线疗效逐步得到验证，公司亦计划开展一项HLX43头对头对比多西他赛的二线临床研究；此外，基于HLX43展现出的低毒及IO功能，复宏汉霖将积极探索推进HLX43的一线治疗方案，开展一项包括单药、联合其他免疫治疗药物以及对比现有标准治疗的三臂试验。同时，HLX43作为全球首个布局胸腺癌的PD-L1 ADC，其国际多中心临床研究在中、美、日、澳等国家同步推进。2025年10月，基于HLX43在胸腺癌后线治疗中优异的初步疗效，该产品获得FDA孤儿药资格认定，有望填补这一罕见高侵袭癌种 ADC治疗的空白。

肺癌和胸腺癌之外，复宏汉霖已累计开展近10项HLX43治疗多项实体瘤中的临床研究，广泛覆盖宫颈癌、食管鳞癌、头颈鳞癌、鼻咽癌、结直肠癌、胃癌/胃食管交界部癌、肝细胞癌等。其中，HLX43在宫颈癌、食管癌等实体瘤领域的概念验证数据也有望于近期读出，为产品的广谱抗肿瘤布局再添关键拼图。单药之外，基于HLX43展现出的IO疗效，公司积极探索HLX43与其他多元分子如公司自研创新抗EGFR单抗HLX07的联合治疗潜力，不断挖掘和最大化该产品在临床中的应用价值。

未来，复宏汉霖将持续深耕肺癌领域，立足于HLX43等核心创新管线，不断放大产品的差异化治疗潜力，加速推动更大临床价值的释放，为全球患者带来更具突破疗效的治疗方案。

Henlius Presents Updated Clinical Data on PD-L1 ADC HLX43 for NSCLC at 2025 International Summit on Frontiers and Innovation in Lung Cancer

• Updated key results for HLX43 in lung cancer released, marking the first combined results from the Phase 2 MRCT in NSCLC, reinforce global clinical profile of the product

• HLX43 demonstrates dual potential as both a best-in-class and best-in-disease candidate, promising to offer breakthrough treatment options for lung cancer patients

• HLX43 received Orphan Drug Designation from the U.S. FDA for TETs; POC data in CC and ESCC are expected soon, continuous to unleashing broad product value

Shanghai, China, November 2, 2025 – Henlius (2696.HK) presented updated key data for its PD-L1 antibody-drug conjugate (ADC) HLX43 in patients with non-small cell lung cancer (NSCLC) at the "2025 International Summit on Frontiers and Innovation in Lung Cancer ". This marks the first time to incorporate results from the multi-regional phase 2 clinical study of HLX43, highlighting the efficacy and safety of the product at the recommended phase 2/3 dose (RP2/3D). The updated findings further validate the promising efficacy of HLX43 in NSCLC, as well as its clinical value across broader patient populations.

HLX43 is a potential best-in-class as well best-in-disease broad-spectrum anti-tumor ADC candidate targeting PD-L1, which exhibits dual mechanisms integrating immune checkpoint blockade and payload-mediated cytotoxicity. Preclinical data have shown that, HLX43 has good anti-tumor effects and a favorable tolerability profile in NSCLC, cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), and other tumor types that were PD-1/L1 mAb-resistant. The results from the phase 1 clinical trial of HLX43 has been first released at the 2025 ASCO Annual Meeting and 2025 WCLC, demonstrating manageable safety profile and encouraging efficacy in various solid tumors especially in patients with NSCLC, including squamous and non-squamous NSCLC patients (sqNSCLC and nsqNSCLC), patients with or without EGFR mutation, patients with or without brain metastasis, and PD-L1 positive or negative patients.

Pooled Analysis at RP2/3D in NSCLC Underpins Global Development Potential of HLX43

Based on the results of prior dose exploration, we prospectively identified 2.0 mg/kg or 2.5 mg/kg as the recommended phase 2/3 dose (RP2/3D) for HLX43 in patients with NSCLC. The updated data released focused on the efficacy and safety of HLX43 the at RP2/3D.  This pooled analysis, which included 174 NSCLC patients who received either 2.0 mg/kg or 2.5 mg/kg Q3W intravenous dosing from two studies, HLX43-FIH101 and HLX43-NSCLC201, aiming to systematically evaluate the efficacy and safety of HLX43 at the RP2/3D, providing a core foundation for decision-making in subsequent pivotal clinical trials.

HLX43-FIH101 is an open-label, first-in-human (FIH) phase I clinical trial conducted in China to evaluate the safety, pharmacokinetics, and preliminary efficacy of HLX43 in patients with advanced/metastatic solid tumors. The study included a dose-escalation phase (phase 1a) to determine the maximum tolerated dose (MTD) across 0.5-4.0 mg/kg, and a dose-expansion phase (phase 1b) focusing on patients with advanced or metastatic NSCLC who had failed standard therapy, evaluating doses from 2.0-3.0 mg/kg to determine the recommended phase 2 dose (RP2D). HLX43-NSCLC201 is an open-label, multi-center international phase 2 clinical trial evaluating the efficacy and safety of HLX43 in patients with advanced NSCLC who had failed at least one prior line of standard therapy. The study is divided into a dose-selection phase (Part A) and a dose-expansion phase (Part B), with the primary endpoint being objective response rate (ORR) as assessed by a blinded independent central review (BICR) per RECIST v1.1.

Updated Key Efficacy Data (including subgroup analysis)

As of October 22, 2025, the pooled analysis included 174 patients with advanced NSCLC. Among them, 89 patients received intravenous HLX43 at 2.0 mg/kg, and 85 patients received 2.5 mg/kg. All enrolled patients (100%) had previously received platinum-based therapy. Approximately 80% and over 30% of patients had previously received immunotherapy and targeted therapy, respectively. Some patients had received docetaxel.

• Significant Efficacy in Overall Population: HLX43 demonstrated significant efficacy across the overall NSCLC population. In sqNSCLC patients receiving 2.0 mg/kg (n=33) HLX43, the investigator-assessed ORR was 33.3%, with a disease control rate (DCR) of 75.8%. Efficacy was more notable in non-squamous NSCLC patients(including EGFR wild type& EGFR mutant) receiving 2.5 mg/kg (n=35), where the ORR reached 48.6% and the DCR was 94.3%

• Superior Efficacy in Docetaxel-Treated Patients: In sqNSCLC patients who had received prior docetaxel treatment (third line or later, n=13), HLX43 achieved an ORR of 38.5% and a DCR of 84.6%, suggesting its important potential in sqNSCLC patients who have failed docetaxel treatment

• Enhanced Benefit in Non-Squamous NSCLC: ORR was 48.6%, with a DCR of 94.3% in nsqNSCLC population (2.5mg/kg, n=35). Notably, ORR was 47.4% for patients with an EGFR wild-type nsqNSCLC (n=19). While in patients with EGFR-mutant nsqNSCLC (n=16), HLX43 received an ORR of 50.0% and a DCR of 93.8%, highlighting superior efficacy of HLX43 in the nsqNSCLC subgroup

• Effective in Brain Metastases: In advanced NSCLC patients with brain metastasis (n=10), HLX43 still delivered significant clinical benefits, with a confirmed ORR (cORR) of 30.0% and DCR of 90.0%

• Efficacy Regardless of PD-L1 Status：Moreover, HLX43 exhibits rubust efficacy in PD-L1 negative (TPS <1%, n=43) patients, with a ORR of 39.5% and DCR of 86.0%, indicating its differented therapeutic potential to cover a broader patient population regardless of PD-L1 expression.

Updated Safety Data

• In terms of safety, the most common grade ≥3 TRAEs were lymphocyte count decreased (9.8%), anemia (8.6%), and neutrophil count decreased (6.3%). Platelet count decreased was reported in 1.7% of all treated patients. HLX43 continued to demonstrate low hematological toxicity, supporting its potential for expansion into first-line setting and combination therapies

• Immune-related AE was reported in 17 (9.8%) patients. Immune-mediated lung disease was reported in 5 (2.9%) patients, all of whom are in recovery

• In these patients with immune-mediated lung disease, the cORR was 40.0% and 100% tumor shrinkage was observed, highlighting the immunotherapeutic effects of HLX43 in addition to its payload-mediated cytotoxic tumor cell killing

Dual-Best Potential Fuels Broad-Spectrum Layout and Clinical Value Realization

The favorable clinical profile of HLX43 originates from its precision design and multiple innovation mechanisms. Compared to ADCs that target driver mutations, HLX43 engages the pan-tumor target PD-L1, demonstrating biomarker-independent and broad-spectrum anti-tumor potential. Its antibody backbone is derived from Henlius's proprietary anti-PD-L1 antibody, HLX20, ensuring high antigen binding and efficient tumor cell internalization. The cleavable linker-payload is licensed from MedLink’s TMALIN^® platform, enables cytotoxic release both intracellularly post-internalization and within the tumor microenvironment. This unique payload release mechanism underpins the molecule's dual mechanism of action, which combines targeted ADC cytotoxicity with immune checkpoint blockade, positioning HLX43 as a promising best-in-class and best-in-disease candidate.

In 2023, HLX43 received IND approvals from both the China National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA) to initiate clinical trials. The company is currently accelerating the clinical development of HLX43. To date, over 400 patients enrolled globally for HLX43, including more than 170 patients with NSCLC. Patient enrollment is progressing steadily across multiple countries including China, the U.S., and Japan. Notably, an international multi-center phase 2 clinical trial in NSCLC is currently being conducted simultaneously in China, the U.S., Japan, Australia, etc. As HLX43's efficacy validated in later-line treatment of NSCLC, Henlius plans to initiate a second-line clinical trial featuring a head-to-head comparison between HLX43 and docetaxel. Furthermore, based on the low toxicity and immuno-oncology (IO) activity demonstrated by HLX43, the company will actively explore and promote the first-line treatment regimens for HLX43, by conducting a three-arm clinical trial that includes monotherapy, combination therapy with an immunotherapeutic agent, and existing standard of care. Meanwhile, as the first PD-L1 ADC developed for thymic carcinoma globally, HLX43 is advancing its international multi-center clinical trials concurrently in China, the U.S., Japan, Australia, etc. In October 2025, based on the compelling preliminary efficacy data from later-line settings in thymic carcinoma (TC), the U.S. FDA granted Orphan Drug Designation (ODD) to HLX43 for the treatment of Thymic epithelial tumors (TETs), highlighting the drug's potential to address the significant unmet need for ADC therapies in this disease.

In addition to NSCLC and TC, Henlius is actively exploring HLX43's therapeutic potential in various solid tumors. The company has initiated 10 clinical studies for HLX43, covering CC, ESCC, head and neck squamous cell carcinoma (HNSCC), nasopharyngeal cancer (NPC), colorectal cancer (CRC), gastric or gastroesophageal junction (G/GEJ) adenocarcinoma and hepatocellular carcinoma (HCC). Proof-of-concept (PoC) data in CC and ESCC are expected to be released in the near future, which will add a critical piece to its broad-spectrum antitumor profile. Building on its intrinsic immuno-oncology (IO) activity, Henlius is exploring combination therapies, such as with the in-house anti-EGFR antibody HLX07, to maximize HLX43's clinical value.

Moving forward, Henlius remains committed to advancing the treatment landscape for lung cancer. By leveraging our core innovative pipeline including HLX43, we will amplify their differentiated therapeutic profile, expedite clinical value delivery, and expand breakthrough treatment options for global patients.

媒体：PR@Henlius.com

投资者：IR@Henlius.com