Core Insights - HUTCHMED's New Drug Application (NDA) for fanregratinib has been accepted and granted priority review by the China National Medical Products Administration (NMPA) for treating advanced intrahepatic cholangiocarcinoma (ICC) patients with FGFR2 fusion/rearrangement who have previously undergone systemic therapy [1][3]. Company Overview - HUTCHMED is an innovative, commercial-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies and immunotherapies for cancer and immunological diseases [5]. - The company retains all global rights to fanregratinib, which is a selective oral inhibitor targeting FGFR 1, 2, and 3 [4]. Industry Context - ICC is the second most common form of liver cancer, accounting for 8.2-15.0% of primary liver cancers, with a rising incidence and a 5-year overall survival rate of approximately 9% [2]. - About 10-15% of ICC patients globally have tumors with FGFR2 fusions or rearrangements, indicating a specific target for fanregratinib [2]. Clinical Data - The NDA is supported by a Phase II registration study in China, which met its primary endpoint of objective response rate (ORR) and showed positive results in secondary endpoints such as progression-free survival (PFS) and overall survival (OS) [3].

香港交易及結算所有限公司及香港聯合交易所有限公司對本公告的內容概不負責，對其準確性或完整性亦不發表任何聲明，並明確表示，概 不對因本公告全部或任何部分內容而產生或因倚賴該等內容而引致的任何損失承擔任何責任。 ― 僅次於肝細胞癌的第二大常見肝癌類型，長期生存率一般相對較差 ― 和黃醫藥（中國）有限公司（簡稱「和黃醫藥」或 「HUTCHMED」）今日宣佈凡瑞格拉替尼 （fanregratinib ，HMPL-453） 用於既往接受過系統性治療，且具有成纖維細胞生長因子受體（「FGFR」）2融合或重排的晚期、轉移性或不可手 術切除的肝內膽管癌（ICC）成人患者的新藥上市申請已獲中國國家藥品監督管理局（「國家藥監局」）受理 ，並獲 納入優先審評。 凡瑞格拉替尼是一種新型、選擇性的FGFR1 、2和3口服抑制劑。肝內膽管癌是一種起源於肝內膽管上皮的具有高度 侵襲性的惡性腫瘤，佔原發性肝癌的約8.2%至15.0% ，是繼肝細胞癌之後第二常見的肝癌類型。近年來，肝內膽管 癌發病率呈持續上升趨勢，5年總生存率約9%。1 全球肝內膽管癌患者中約有10-15％伴有FGFR2融合或重排。2,3 一項在中國開展的單臂、多中心、開放標 ...

Core Insights - 2025 marks a pivotal year for China's innovative pharmaceuticals, with a significant increase in international collaborations and licensing agreements, indicating a shift from a pharmaceutical giant to a stronghold in the industry [1][3] - The total amount of outbound licensing agreements exceeded $100 billion, with upfront payments reaching $8.1 billion, showcasing a transition to multi-layered cooperation models [1][3] - China's biopharmaceutical market remains the second largest globally, with innovative drugs accounting for approximately 30% of global research, reflecting a critical leap from following to competing on a global scale [1][3] Internationalization - The internationalization of China's pharmaceutical industry saw explosive growth in 2025, highlighted by a surge in business development (BD) transactions and the popularity of "A+H" listings [3][4] - The total amount of outbound licensing for innovative drugs reached over $100 billion, a 75% increase from 2024, indicating a shift from merely selling products to actively engaging in global markets [3][4] - Notable BD transactions include significant agreements between major Chinese pharmaceutical companies and international firms, such as a $12.5 billion deal between Hengrui Medicine and GSK [3][4] Innovation - In 2025, advancements in cutting-edge technologies such as antibody-drug conjugates (ADC) and dual antibodies have shown promising results in cancer treatment [7][8] - The third-generation ADC technology has become mainstream, with significant efficacy demonstrated in treating solid tumors [7] - The dual antibody sector continues to lead, with Chinese companies achieving remarkable results in clinical trials, such as a 91% improvement in progression-free survival compared to existing treatments [8] Policy Support - The policy support for innovative drugs in China has reached unprecedented levels, with a notable increase in the number of approved innovative drugs [10][11] - The National Medical Products Administration approved 69 innovative drugs in 2025, a 44% increase from the previous year, covering various therapeutic areas [10] - The payment system for innovative drugs has been significantly upgraded, enhancing accessibility and affordability for patients [10][11] Mergers and Acquisitions - The pharmaceutical sector has seen a surge in mergers and acquisitions, with over 400 transactions announced globally, totaling approximately $111 billion, marking a 50% increase from 2024 [13][14] - Domestic mergers also showed strong activity, with significant deals indicating a shift towards quality improvement and resource consolidation among leading companies [13][14] - The trend reflects a transition from scale expansion to enhancing quality and efficiency, with companies focusing on high-value clinical pipelines [14]

Core Viewpoint - Hutchison China MediTech Limited (HCM) has initiated global Phase I clinical development for HMPL-A251, a first-in-class PI3K/PIKK-HER2 antibody-drug conjugate (ATTC) designed to target HER2-expressing tumors [1][2]. Group 1: Clinical Development - The Phase I/IIa trial is an open-label, multicenter study aimed at evaluating the safety and efficacy of HMPL-A251 in adult patients with unresectable, HER2-expressing advanced or metastatic solid tumors [2]. - The study consists of two phases: the Phase I dose escalation phase and the Phase IIa dose expansion and optimization phase, focusing on determining the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) [2]. - Primary endpoints include safety, tolerability, and preliminary efficacy, while secondary endpoints encompass initial anti-tumor activity, pharmacokinetics, and immunogenicity of HMPL-A251 [2]. Group 2: Drug Characteristics - HMPL-A251 is the first candidate from HCM's new generation ATTC platform, utilizing a potent and selective PI3K/PIKK inhibitor as the payload [2]. - The drug is designed to precisely target HER2-expressing tumor cells, potentially overcoming systemic toxicity and narrow therapeutic windows associated with traditional PI3K/PIKK inhibitors [2]. - The strategy aims to enhance overall tolerability while achieving more effective and sustained pathway inhibition [2]. Group 3: Preclinical Data - Preclinical data for HMPL-A251 was presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targeted Therapy and Cancer [3]. - These data support the translational potential of the ATTC platform and the ongoing global clinical evaluation of HMPL-A251 [3]. - The combination of PI3K/PIKK inhibitors with linker-payload technology shows promise for developing a series of future ATTC candidates [3].

Core Insights - Hutchison China MediTech Limited (HCM) has announced the initiation of global Phase I clinical development for HMPL-A251, a first-in-class PI3K/PIKK-HER2 antibody-drug conjugate (ADC) [1][2] - The study aims to evaluate the safety and efficacy of HMPL-A251 in adult patients with unresectable, HER2-expressing advanced or metastatic solid tumors [1] Group 1: Clinical Development - HMPL-A251 is the first candidate from HCM's next-generation ADC platform to enter clinical development [2] - The clinical trial will be conducted in the United States and China, with the first patient dosed on December 16, 2025 [1] - The study consists of a Phase I dose-escalation stage and a Phase IIa dose-expansion and optimization stage, focusing on safety, tolerability, and preliminary efficacy [1] Group 2: Mechanism and Innovation - HMPL-A251 utilizes a highly selective and potent PI3K/PIKK inhibitor as the payload, coupled with a humanized anti-HER2 IgG1 antibody via a cleavable linker [1][2] - This innovative approach aims to target HER2-expressing tumor cells precisely, potentially overcoming systemic toxicity and narrow therapeutic windows associated with traditional PI3K/PIKK inhibitors [2] - Preclinical data supporting the potential of the ADC platform were presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targeted Therapy and Cancer [2]

Core Viewpoint - Hutchison China MediTech Limited (00013.HK) has announced the initiation of global Phase I clinical development for HMPL-A251, a first-in-class PI3K/PIKK-HER2 antibody-drug conjugate (ATTC) [1] Group 1 - HMPL-A251 is composed of a highly selective and potent PI3K/PIKK inhibitor as the payload and a humanized anti-HER2 IgG1 antibody linked by a cleavable linker [1] - The clinical study will be conducted in both the United States and China [1] - The first patient received the initial dose of treatment on December 16, 2025, in China [1]

香港交易及結算所有限公司及香港聯合交易所有限公司對本公告的內容概不負責，對其準確性或完整性亦不發表任何聲明，並明確表示，概 不對因本公告全部或任何部分內容而產生或因倚賴該等內容而引致的任何損失承擔任何責任。 HUTCHMED (China) Limited 和黃醫藥（中國）有限公司 （於開曼群島註冊成立的有限公司） 和黃醫藥啓動ATTC候選藥物HMPL-A251用於治療實體瘤的全球臨床開發 — 新一代 ATTC 平台下候選藥物首次進入人體臨床試驗 ― ― 中國與全球同步臨床開發策略，加速推進研發進程 ― 和黃醫藥（中國）有限公司（簡稱「和黃醫藥」或 「HUTCHMED」）今日宣佈啟動HMPL-A251的全球I期臨床開發 項目。 HMPL-A251 是一款全球首創的PI3K/PIKK- HER2抗體靶向偶聯藥物（「ATTC」），由高選擇性、強效的 PI3K/PIKK抑制劑作為有效載荷（payload）和人源化抗HER2 IgG1抗體通過可裂解的連接子（linker）偶聯而成。 研究將於美國和中國開展。首名患者已於2025年12月16日於中國接受首次給藥治療。 這項首個人體試驗是一項 I/IIa 期、開放標簽、多 ...

Core Insights - HUTCHMED has initiated a global Phase I clinical development program for HMPL-A251, a first-in-class PI3K/PIKK-HER2 Antibody-Targeted Therapy Conjugate, with the first patient dosed on December 16, 2025 [1][2] Group 1: Clinical Development - The Phase I/IIa study evaluates HMPL-A251 monotherapy in adult patients with unresectable, advanced or metastatic HER2-expressing solid tumors, focusing on safety, tolerability, and determining maximum tolerated doses [2][3] - The study is divided into two parts: Phase I for dose escalation and Phase IIa for dose expansion and optimization, with primary outcomes including safety and preliminary efficacy [2][3] Group 2: Product Details - HMPL-A251 is derived from HUTCHMED's next-generation ATTC platform, designed to deliver targeted pathway inhibition directly into HER2-expressing tumor cells, potentially overcoming systemic toxicity associated with traditional PI3K/PIKK inhibitors [3][4] - The ATTC platform combines monoclonal antibodies with small-molecule inhibitor payloads, aiming for synergistic anti-tumor activity and improved safety profiles compared to traditional therapies [5][6] Group 3: Mechanism of Action - The PI3K/AKT/mTOR (PAM) pathway is critical for cell growth and survival, with alterations linked to poor prognosis in various cancers; HMPL-A251 aims to address challenges faced by existing PAM-targeted drugs [7][8] - The innovative design of HMPL-A251 enhances targeted delivery to tumor cells, maximizing therapeutic benefits while minimizing systemic exposure [9]

Investment Rating - The report does not explicitly provide an investment rating for the industry Core Insights - The report highlights the strategic cooperation between China and France in addressing global climate and environmental challenges, emphasizing the importance of multilateralism and the implementation of international agreements such as the Paris Agreement [5][6][9] - The report indicates that China's carbon emissions growth has significantly slowed, with a 0.6% increase in 2024 compared to 2023, which is lower than the global average of 0.8% [17][19] - The establishment of a green foreign debt pilot program in Shanghai aims to support "dual carbon" key enterprises, with over 300 million RMB in financing for green technology projects [20][22] Policy Developments - China and France issued a joint statement on climate cooperation during President Macron's visit, reaffirming their commitment to international climate agreements and cooperation in various areas such as carbon pricing and methane reduction [5][6][7] - The China Securities Regulatory Commission (CSRC) is seeking public opinion on a draft regulation aimed at enhancing corporate governance and investor protection in listed companies [11][12][13] Industry Trends - The Ministry of Ecology and Environment released the "2025 China Mobile Source Environmental Management Annual Report," indicating that mobile sources are a significant contributor to air pollution, with total emissions reaching 18.582 million tons in 2024 [14][15][16] - The "2024 China Greenhouse Gas Bulletin" shows that China's anthropogenic carbon emissions increased by approximately 0.6% in 2024, reflecting effective implementation of carbon reduction commitments [17][19] - The Shanghai branch of the State Administration of Foreign Exchange has initiated a green foreign debt pilot program, with three key enterprises signing agreements to raise over 300 million RMB for green projects [20][22] International Events - The United Nations Environment Programme (UNEP) released the 2025 Climate Adaptation Gap Report, highlighting a significant funding gap for climate adaptation in developing countries [24][25] - Former President Trump announced plans to roll back fuel economy standards, which could impact environmental progress in the U.S. automotive industry [26][27][28] - Germany's government has agreed to construct hydrogen-compatible gas power plants, potentially delaying the coal phase-out process [29] Corporate Developments - China Gas and EVE Energy have entered a strategic partnership to collaborate on energy storage and green energy projects [30][31] - Hutchison Whampoa has been recognized as an "ESG Leading Company" for three consecutive years, reflecting its commitment to sustainability and responsible governance [32][33]

Investment Rating - The report maintains a "Positive" investment rating for the pharmaceutical and biotechnology industry, indicating an expected return that is stronger than the market benchmark by over 5% [5]. Core Insights - The National Medical Insurance Administration is strongly encouraging the high-quality development of innovative drugs, with clear policies supporting the payment side for innovative drugs. Domestic leading innovative drug companies are entering a commercial realization phase [3][7]. - The 2025 National Medical Insurance Drug List includes 127 products, with 114 successfully added, of which 50 are innovative drugs, marking a historical high. The overall negotiation success rate reached 90%, the highest in nearly seven years [7]. - The report highlights that the domestic innovative drug market is becoming increasingly concentrated, with leading companies like Heng Rui and Xin Da Biotech significantly benefiting from the new insurance policies [7]. Summary by Sections Investment Recommendations and Targets - Recommended stocks include Heng Rui Pharmaceutical (600276, Buy), Ke Lun Pharmaceutical (002422, Buy), Xin Li Tai (002294, Hold), Ao Sai Kang (002755, Buy), Jing Xin Pharmaceutical (002020, Buy), and others [3]. Market Dynamics - The report notes that the introduction of the commercial insurance directory marks the beginning of a "new golden decade" for Chinese innovative drugs, with a focus on high clinical efficacy and value innovation [7]. - The report emphasizes that the competition in the GLP-1 market remains clear, with the entry of new drugs not significantly altering the competitive landscape for existing treatments [7].