Core Viewpoint - The company has announced mid-term data from a Phase II clinical trial of its dual-targeting bispecific antibody M701 for treating malignant pleural effusion caused by advanced non-small cell lung cancer (NSCLC), showing significant efficacy compared to the control group receiving cisplatin [1][4]. Group 1: Clinical Trial Overview - The Phase II trial (code name: M70103) is a randomized, controlled, multi-center study involving 54 eligible patients with symptomatic malignant pleural effusion after at least one line of systemic therapy [2]. - Patients were randomly assigned in a 1:1 ratio to receive either M701 or cisplatin after thoracentesis [1][2]. - The primary endpoint is puncture-free survival time (Pu FS), while secondary endpoints include objective response rate (ORR), time to next puncture (TTNP), and related symptoms [1]. Group 2: Patient Demographics - The trial included 26 patients in the M701 group and 28 in the cisplatin group, with median ages of 66.5 and 61.5 years, respectively [2]. - Female proportions were 57.7% in the M701 group and 50.0% in the control group, with ECOG performance status scores of 0-1 being 92.3% and 96.4% [2]. - Baseline characteristics were generally balanced between the two groups, with similar proportions of patients having prior thoracentesis and chemotherapy [2]. Group 3: Efficacy Results - M701 demonstrated a longer median puncture-free survival time compared to cisplatin (130 days vs. 85 days, HR=0.80, p=0.542) [3]. - In patients without driver gene mutations, the median survival was not reached for M701 compared to 44.5 days for cisplatin (HR<0.01, p<0.001) [3]. - The objective response rate for malignant pleural effusion was 72.7% for M701 versus 41.7% for cisplatin [3]. Group 4: Safety Results - The incidence of treatment-related adverse events was 3.7% for M701 compared to 10% for cisplatin, with only one serious adverse event related to M701 [3]. - Flow cytometry analysis indicated a significant reduction of Ep CAM+CD45- tumor cells in the pleural effusion after M701 infusion, which was not observed in the cisplatin group [3]. Group 5: Conclusion and Future Plans - M701 shows significant efficacy and good tolerability in treating malignant pleural effusion, particularly in NSCLC patients without driver gene mutations or those with prior chemotherapy [4]. - The ongoing Phase II trial indicates potential for preventing recurrence of pleural effusion, with plans for a pivotal Phase III trial to start in 2026 to validate efficacy and safety in a larger Chinese population [4].

疗效结果：试验组的无穿刺生存时间长于对照组(中位值130天对85天，HR(风险比)=0.80，p=0.542)，而 对于驱动基因阴性的患者(中位值未达到对44.5天，HR<0.01，p<0.001)或有胸腔内化疗史的患者(中位值 253天对72天，HR=0.31，p=0.076)，其获益更加显著。在上述人群中，试验组和对照组的恶性胸水客观 缓解率(MPE ORR)分别为72.7%和41.7%。随机分组98天后，只有试验组受试者的呼吸困难症状持续改 善。流式细胞术分析显示，输注M701后，胸水中的Ep CAM+CD45-肿瘤细胞显著减少，而在输注顺铂 的对照组中则没有这种现象。 安全性结果：M701治疗相关不良事件发生率为3.7%，顺铂组为10%，仅1例严重不良事件(2级发热)与 M701相关。 截至2025年3月7日，54名筛选合格的经至少一线全身治疗后病情进展、有症状性恶性胸水的晚期非小细 胞肺癌(NSCLC)患者，按照1:1随机分组，试验组26名，对照组28名。试验组的中位年龄为66.5岁，对照 组的中位年龄为61.5岁。试验组和对照组女性比例分别为57.7%和50.0%，体力状态评分(ECOG)处于0– ...

Core Viewpoint - Huahai Pharmaceutical's subsidiary, Shanghai Huatai Biopharmaceutical Co., Ltd., has received FDA approval to conduct Phase I clinical trials for HB0043 in the United States, marking a significant advancement in the treatment of autoimmune diseases [1] Group 1: Product Development - HB0043 is a recombinant humanized IgG1 bispecific antibody targeting both IL-17A and IL-36R, demonstrating high binding and blocking activity [1] - The drug is developed for treating various difficult-to-treat autoimmune diseases, showing stronger efficacy in animal models compared to monoclonal antibodies [1] - HB0043 is the world's first bispecific antibody targeting IL-17A and IL-36R, potentially overcoming the limitations of existing single-target therapies [1] Group 2: Market Potential - Current IL-17A inhibitors and IL-36R monoclonal antibodies have shown positive effects in multiple indications, but there are still limitations in their single-dimensional intervention for some patients [1] - The dual-target approach of HB0043 is expected to provide new treatment strategies for immune-mediated inflammatory skin diseases and fibrotic diseases [1] - The innovative mechanism of HB0043 positions it as a first-in-class (FIC) product with broad potential applications in Th17 and IL-36 related immune-mediated diseases [1]

Core Insights - Huahai Pharmaceutical's subsidiary, Shanghai Huatai Biopharmaceutical Co., Ltd., has received approval from the National Medical Products Administration for the clinical trial of HB0043, a bispecific antibody targeting IL-17A and IL-36R, aimed at treating various autoimmune diseases [1][2] Group 1: Product Development - HB0043 is a recombinant humanized IgG1 bispecific antibody that targets both IL-17A and IL-36R, demonstrating high binding and blocking activity [1] - The drug has shown superior efficacy compared to monoclonal antibodies in various animal disease models, including atopic dermatitis, idiopathic pulmonary fibrosis, diabetic nephropathy, and neutrophilic asthma [1] - HB0043 offers a new approach to targeted therapy for immune-mediated inflammatory skin diseases and fibrotic diseases, addressing the limitations of single-factor blocking therapies [1] Group 2: Market Potential - As the first bispecific drug globally targeting both IL-17A and IL-36R, HB0043 is expected to overcome the limitations of existing single-target therapies [2] - Current treatments, such as IL-17A inhibitors and IL-36R monoclonal antibodies, have shown positive effects in multiple indications but may still fall short in addressing inflammation in some patients [2] - The innovative dual-target mechanism of HB0043 positions it as a first-in-class (FIC) therapy with broad potential applications in various Th17/IL-36 related immune-mediated diseases [2]