Analyst Ratings - Weiss Ratings restated a "hold (c-)" rating on Pharming Group shares [1] - Zacks Research upgraded Pharming Group from "hold" to "strong-buy" [1] - Wall Street Zen also upgraded Pharming Group to a "strong-buy" rating [1] - The average rating for Pharming Group is "Buy" with a consensus target price of $38.00 [1] Financial Performance - Pharming Group has a market capitalization of $1.21 billion and a P/E ratio of -1,765.23 [2][3] - The company reported earnings of $0.10 per share, exceeding analysts' expectations of $0.05 by $0.05 [4] - Revenue for the quarter was $97.30 million, slightly below the consensus estimate of $98.22 million [4] - The company has a quick ratio of 2.39, a current ratio of 3.16, and a debt-to-equity ratio of 0.35 [2][3] Stock Performance - Pharming Group's share price increased by 4.4% to $17.55, with a trading volume of approximately 5,296 shares [8] - The stock had previously closed at $16.81 and traded as high as $17.32 during the day [8] Institutional Activity - EverSource Wealth Advisors LLC purchased 2,979 shares of Pharming Group, valued at approximately $32,000 [5] - Institutional investors currently own 0.03% of Pharming Group's stock [5] Company Overview - Pharming Group N.V. is a clinical-stage biopharmaceutical company based in Leiden, Netherlands, focusing on innovative protein replacement therapies for rare diseases [6] - The company's lead product, RUCONEST, is approved for treating acute hereditary angioedema (HAE) attacks in multiple markets [7]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 代谢功能障碍相关脂肪性肝病 （MAFLD） 是 肝细胞癌 （HCC） 的主要诱因，由于代谢压力导致的 异常 免疫微环境 ，其治疗颇具挑战性。然而，目前尚无针对 MAFLD 肝脏微环境重塑的有效药物疗法。 近日，清华大学 喻国灿 团队联合 浙江大学医学院附属第一医院 章琦 团队，在 Science 子刊 Science Translational Medicine 上发表了 题为： Metabolism-programming mRNA-lipid nanoparticles remodel the immune microenvironment to improve immunotherapy against MAFLD 的研究论文。 该研究开发了一种维生素 E 功能化的 LNP—— Def-LNP ，用于递送编码 T 细胞蛋白酪氨酸磷酸酶 （TCPTP） 的 mRNA，以重新编程肝脏 STAT 信号转导，同时不刺激氧化应激。在多个哺乳动物临床前 模型中，使用 Def-LNP 递送 TCPTP mRNA 改善了脂肪性肝炎和代谢及免疫平衡，并减少了肝细胞癌的 进展。 这项 ...

Core Insights - The article discusses the potential of circular RNA (circRNA) as a next-generation RNA therapy platform, highlighting its advantages over traditional mRNA therapies, particularly in stability, immunogenicity, and safety [2][4]. Group 1: CircRNA Advantages - CircRNA exhibits superior stability, immunogenicity, and safety compared to chemically modified mRNA and viral vector-based therapies [2]. - CircRNA can utilize internal ribosome entry site (IRES) sequences, eliminating the need for expensive 5' cap modifications and resulting in lower immunogenicity without chemical modifications [2]. Group 2: Research Findings - A study published in Nature Communications demonstrates that circRNA-based protein replacement therapy can alleviate osteoarthritis in male mice [3][4]. - Osteoarthritis (OA) is characterized by cartilage degradation and bone spur formation, with recent research indicating that the expression of Na v 1.7 in chondrocytes leads to cartilage degeneration and pain [6]. Group 3: Mechanism and Treatment Strategy - The study identifies that the downregulation of the RNA-binding protein Musashi2 (MSI2) in chondrocytes is a key factor in the pathogenesis of osteoarthritis [7]. - A local delivery strategy was developed to achieve high and sustained protein expression in chondrocytes, demonstrating that injecting ivcRNA encoding MSI2 effectively slows the progression of osteoarthritis in a mouse model [7][9].