4-1BB激动剂
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4-1BB:复盘历史失败原因,维立志博做对了什么?
Huafu Securities· 2025-11-23 09:20
Investment Rating - The industry investment rating is "Outperform" [1] Core Viewpoints - The report emphasizes the potential of second-generation 4-1BB agonists, particularly dual-target antibodies, which have shown promising efficacy while addressing safety concerns associated with liver toxicity [4][24] - The report highlights significant recent industry events, including Merck's acquisition of Cidara for approximately $9.2 billion and Pfizer's acquisition of Metsera, indicating a trend of consolidation in the biopharmaceutical sector [6] - The report suggests a long-term positive outlook for China's innovative drug sector, driven by increasing data catalysts and new product sales, recommending specific companies for investment [6] Summary by Sections 4-1BB Overview - 4-1BB (CD137) is a key member of the tumor necrosis factor receptor superfamily, crucial for T cell activation and immune response enhancement [4][10] - The second-generation CAR-T cell technology utilizing 4-1BB has been validated for inducing prolonged activation and survival of CAR-T cells in vivo [4][12] First-Generation 4-1BB Agonists - First-generation 4-1BB agonists like urelumab and utomilumab faced limitations due to liver toxicity and insufficient efficacy [16][22] - Urelumab demonstrated significant hepatotoxicity at doses ≥1.0 mg/kg, leading to its discontinuation [21][22] Second-Generation 4-1BB Agonists - Second-generation 4-1BB agonists are primarily dual-specific antibodies targeting various pathways, with a focus on balancing efficacy and safety [24][26] - LBL-024, a promising candidate, has shown unprecedented efficacy and is expected to submit a BLA by Q3 2026 [4][6] Recent Industry Events - Merck's acquisition of Cidara for $9.2 billion and Pfizer's acquisition of Metsera highlight ongoing consolidation in the biopharmaceutical industry [6] - The report notes that the innovative drug sector is under pressure but is expected to rebound with a focus on companies with strong revenue capabilities [6] Investment Strategy - The report recommends focusing on companies with differentiated innovation pipelines and strong revenue capabilities, including specific biopharma and pharma leaders [6] - Suggested companies for investment include Innovent Biologics, BeiGene, and I-MAB, among others [6]