（原标题：和黄医药(00013)启动ATTC候选药物HMPL-A251用于治疗实体瘤的全球临床开发） 智通财经APP讯，和黄医药(00013)发布公告，启动HMPL-A251的全球I期临床开发项目。 HMPL-A251 是一款全球首创的PI3K/PIKK- HER2抗体靶向偶联药物("ATTC")，由高选择性、强效的 PI3K/PIKK抑制 剂作为有效载荷(payload)和人源化抗HER2 IgG1抗体通过可裂解的连接子(linker)偶联而成。研究将于美 国和中国开展。首名患者已于2025年12月16日于中国接受首次给药治疗。 这项首个人体试验是一项 I/IIa 期、开放标签、多中心临床研究，旨在评估HMPL-A251单药用于治疗不 可切除、伴有HER2 表达的晚期或转移性实体瘤成人患者。研究分为两个阶段：I 期剂量递增阶段和 IIa 期剂量扩展及优化阶段。研究的主要指标为HMPL-A251的安全性和耐受性 ，在I期部分确定最大耐受剂 量(MTD)和/或剂量扩展推荐剂量(RDE)， 并进一步评估RDE下的安全性和初步疗效，及在IIa期部分确 定II期(RP2D)或III期(RP3D)临床试验推荐剂量。次要 ...

格隆汇12月17日丨和黄医药(00013.HK)宣布启动HMPL-A251的全球I期临床开发项目。 HMPL-A251是 一款全球首创的PI3K/PIKK- HER2抗体靶向偶联药物("ATTC")，由高选择性、强效的PI3K/PIKK抑制剂 作为有效载荷(payload)和人源化抗HER2 IgG1抗体通过可裂解的连接子(linker)偶联而成。研究将于美国 和中国开展。首名患者已于2025年12月16日于中国接受首次给药治疗。 ...

Core Viewpoint - The Hong Kong stock market has seen a significant rise in the healthcare sector, with the Hang Seng Healthcare Index reaching a maximum increase of 102.6% this year, although it has since corrected to a still substantial 70.57% increase. In contrast, Hutchison China MediTech (HCM) has underperformed, with a maximum increase of only 36.36% and a recent drop to just 5.19% [1] Market Performance - HCM's stock price has fluctuated between the middle and upper Bollinger Bands since early April, reflecting the overall bullish trend in the Hong Kong innovative drug sector. However, the release of its mid-year report on August 7 marked a turning point, leading to a decline in market sentiment [2] - Following the mid-year report, HCM's stock plummeted by 15.99% on August 8, with trading volume reaching a record high of 70.29 million shares, indicating increased market panic and a significant shift in investor sentiment [3] Investor Behavior - The trading behavior of HCM's stock has shown signs of speculative trading rather than long-term holding, with notable fluctuations in trading volume and price changes on specific dates [3] - Recent data indicates that major banks and investment firms have shifted their positions, with significant net buying from Bank of China and other channels, while major sellers include HSBC and Citibank [4] Financial Performance - HCM reported a revenue of $278 million for the first half of 2025, a decrease of 9.2% year-on-year. However, net profit surged to $455 million, a 16.6-fold increase, primarily due to the sale of non-core joint venture stakes. Despite this, sales of its three main innovative drugs fell sharply by 30-50%, leading to a 22% decline in proprietary product sales [2][6] Product Pipeline and Future Prospects - HCM's core products have faced significant domestic market challenges, with sales of Elunate, Sulanda, and Orpathys declining by 29%, 50%, and 41% respectively due to increased competition and market pressures [6] - Despite domestic setbacks, HCM's overseas sales, particularly for Elunate, have shown growth, with a 25% increase to $163 million, indicating potential for recovery in international markets [6][7] - The company is focusing on new product development, with the recent acceptance of HMPL-A251 for clinical trials, which combines targeted therapies and may offer new treatment options [7][8]

Core Viewpoint - Huadong Medicine (00013) has significant potential in its innovative pipeline, with a "Buy" rating maintained by Huayuan Securities, projecting total revenues of $567 million, $676 million, and $816 million for 2025-2027 [1] Group 1: Event Highlights - Huadong Medicine shared key R&D and business progress during an investor meeting on October 31, 2025, focusing on advancements in innovative cancer and immune disease treatments, including its next-generation Antibody-Drug Conjugate (ATTC) platform and late-stage pipeline candidates [1] Group 2: Breakthrough ATTC Platform and Pipeline Potential - The ATTC platform is a proprietary cancer precision therapy drug development platform that connects monoclonal antibodies with patented targeted small molecule payloads, aiming for superior anti-tumor activity and safety compared to traditional Antibody-Drug Conjugates (ADC) [2] - The first potential pipeline from this platform is HMPL-A251, a PAM-HER2ATTC that combines a highly selective and potent PI3K/PIKK inhibitor as the payload with a humanized anti-HER2 IgG1 antibody via a cleavable linker, showing promising anti-tumor efficacy and tolerability in preclinical studies [2] - Based on preclinical data, Huadong Medicine plans to advance HMPL-A251 into clinical development starting at the end of 2025 [2] Group 3: Ongoing Late-Stage Projects - The FRUSICA-2 study of fruquintinib combined with sintilimab for second-line treatment of renal cell carcinoma will present data at the 2025 ESMO conference, showing a median progression-free survival (mPFS) of 22.2 months and an overall response rate (ORR) of 60.5% [3] - The SANOVO China Phase III study for savolitinib in first-line treatment of EGFR-mutant non-small cell lung cancer with MET overexpression has completed patient recruitment, while the SAFFRON global Phase III study for second-line treatment is progressing well, expected to complete recruitment by the end of 2025 [3] - The study of surufatinib for pancreatic cancer, in combination with carrelizumab, albumin-bound paclitaxel, and gemcitabine, is progressing well, with Phase II results to be announced at an upcoming scientific meeting [3] - The Chinese registration Phase II study of HMPL-453 for advanced intrahepatic cholangiocarcinoma has completed recruitment, with plans to submit a new drug application in the first half of 2026 [3]

Core Viewpoint - Huadong Medicine (00013) has significant potential in its innovative pipeline, with a "Buy" rating maintained by Huayuan Securities, projecting total revenues of $567 million, $676 million, and $816 million for 2025-2027 respectively. The calculated fair equity value of the company is HKD 26.9 billion based on a DCF model with a perpetual growth rate of 2% and a WACC of 9.43% [1] Group 1: Breakthrough ATTC Platform and Pipeline Potential - The ATTC platform is a proprietary cancer precision therapy drug development platform that connects monoclonal antibodies with patented targeted small molecule inhibitors, aiming for dual action mechanisms. This platform is expected to offer superior anti-tumor activity and safety compared to traditional ADCs [2] - The first potential pipeline from this platform is HMPL-A251, a PAM-HER2 ATTC that combines a highly selective and potent PI3K/PIKK inhibitor with a humanized anti-HER2 IgG1 antibody via a cleavable linker. Preclinical studies have shown promising anti-tumor efficacy and tolerability, with plans to advance HMPL-A251 into clinical development by the end of 2025 [2] Group 2: Ongoing Late-Stage Projects and Future Prospects - The FRUSICA-2 study on fruquintinib combined with sintilimab for second-line treatment of renal cell carcinoma will present data at the 2025 ESMO conference, showing a median progression-free survival (mPFS) of 22.2 months and an overall response rate (ORR) of 60.5% [3] - The SANOVO China Phase III study for savolitinib in first-line treatment of EGFR-mutant non-small cell lung cancer (NSCLC) with MET overexpression has completed patient recruitment, while the SAFFRON global Phase III study for second-line treatment is progressing well, expected to complete recruitment by the end of 2025 [3] - The ongoing Phase II/III study of surufatinib combined with carrelizumab, albumin-bound paclitaxel, and gemcitabine for first-line treatment of metastatic pancreatic ductal adenocarcinoma is progressing smoothly, with Phase II results to be announced at an upcoming scientific conference [3] - The Chinese registration Phase II study of HMPL-453 for advanced intrahepatic cholangiocarcinoma has completed recruitment, with plans to submit a new drug application in the first half of 2026 [3]

Core Viewpoint - Hutchison China MediTech Limited (HCM) is set to present preclinical data for HMPL-A251, a novel PI3K/AKT/mTOR (PAM)-HER2 antibody-drug conjugate (ATTC), at the AACR-NCI-EORTC International Conference on Molecular Targeted Therapy and Cancer Therapeutics in Boston from October 22 to 26, 2025 [1] Group 1: Product Overview - HMPL-A251 is designed to combine HER2-targeted therapy with PAM pathway inhibition, aiming to overcome the limitations of traditional antibody-drug conjugates (ADCs) and single PAM inhibitors [1] - The drug utilizes a highly selective and potent PI3K/PIKK inhibitor as the payload, conjugated to a humanized anti-HER2 IgG1 antibody via a cleavable linker [1] Group 2: Preclinical Efficacy - In vitro studies show that the PI3K/PIKK inhibitor payload exhibits strong, selective, and broad anti-tumor activity across 130 tumor cell lines [2] - HMPL-A251 demonstrates HER2-dependent anti-tumor activity, effectively inhibiting the growth of HER2-positive tumor cells regardless of PAM pathway alterations [2] - The compound also shows a bystander effect on HER2-negative cells when co-cultured with HER2-positive cells [2] Group 3: Safety and Efficacy - The ATTC design emphasizes the precise delivery of regulatory pathway-modulating payloads to tumor tissues, enhancing long-term safety compared to traditional ADCs [3] - HMPL-A251 has shown superior anti-tumor efficacy and tolerability compared to naked antibodies and payload combination therapies in in vivo models [3] - The drug induces tumor regression in various models, including HER2-positive and low HER2 expression models, with efficacy closely linked to payload concentration and target inhibition [3] Group 4: Future Development Plans - HCM plans to initiate global clinical trials for HMPL-A251 by the end of 2025 and submit multiple global new drug clinical trial applications for other ATTC candidates in 2026 [4] - The ATTC platform represents a new generation of precision cancer therapies, combining monoclonal antibodies with proprietary targeted small molecule inhibitors for dual action mechanisms [4][5]