Core Viewpoint - The increasing prevalence of metabolic dysfunction-related fatty liver disease (MASH) necessitates the development of new therapeutic strategies, as current treatment options are limited and the patient population is growing rapidly [2][5]. Group 1: MASH Overview - Approximately 100 million people globally are currently affected by MASH, with projections indicating this number could rise to 357 million by 2030 [2]. - MASH is a critical factor in the progression of liver cirrhosis and hepatocellular carcinoma, and it is a leading cause of liver transplants [2]. Group 2: Research Findings - A new strategy for large-scale acquisition of artificial cell-derived vesicles (ACDV) has been proposed, which allows for the safe and stable oral delivery of RNA drugs targeting the liver [3]. - The study demonstrated that LIMA1 siRNA (siLIMA1) delivered via the modified ACDV effectively inhibited LIMA1 protein expression in the liver, thereby preventing MASH progression and improving liver function [3][11]. Group 3: Mechanism of Action - The development of drugs targeting metabolism, inflammation, and fibrosis is crucial, as excessive accumulation of fats and other metabolic substrates leads to chronic inflammation and liver cell damage [5]. - LIMA1 gene silencing is identified as a promising therapeutic approach for MASH, given its upregulation in lipotoxic liver cells and its role in liver fibrosis associated with metabolic dysfunction [5][6]. Group 4: Delivery System - The study highlights the potential of red blood cell (RBC)-derived extracellular vesicles (RBC-EV) as a non-immunogenic delivery option for RNA drugs, although challenges remain in large-scale production and half-life limitations [7]. - A feasible strategy involves generating ACDV by squeezing red blood cells, which can then be modified with DSPE-PEG and cholic acid to enhance structural integrity and liver-targeting capabilities [8][9]. Group 5: Conclusion - The research indicates that ACDV can be easily obtained and modified to achieve oral liver-targeting capabilities, with the delivery of LIMA1-siRNA showing significant therapeutic effects against MASH [13].

Core Points - Inventiva, a clinical-stage biopharmaceutical company, focuses on developing oral therapies for metabolic dysfunction-associated steatohepatitis (MASH) and announced the results of its Combined Shareholders' Meeting [1][12] - The meeting took place on May 22, 2025, in Paris, chaired by CEO Frédéric Cren [2] - All resolutions were adopted except for the 33rd resolution, which was negatively recommended by the Board of Directors [3] Voting Results - The shareholders present included 245 participants, representing a total of 90,772,892 shares and 102,984,957 votes, achieving a quorum of 65.264% [5] - Ordinary resolutions were overwhelmingly adopted, with the first resolution receiving 99.98% approval [6][10] - The 33rd resolution, which would have allowed the Board to decide on share capital increases for a company savings plan, was rejected with 90.58% against [10][11] Company Overview - Inventiva is publicly listed on Euronext Paris and Nasdaq, focusing on the research and development of oral small molecule therapies for MASH and other unmet medical needs [12][13] - The company is currently evaluating lanifibranor in a pivotal Phase 3 clinical trial for MASH treatment [12]

Core Viewpoint - Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are increasingly serious public health burdens with limited treatment options. Recent studies indicate that fibroblast growth factor-21 (FGF21) analogs can significantly improve MASH, although the mechanisms remain unclear [2]. Group 1 - A study published by researchers from the University of Iowa in Cell Metabolism demonstrates that FGF21 reverses MASH through coordinated actions on the central nervous system (CNS) and liver [3]. - The research team established that FGF21 exerts beneficial metabolic effects to reverse MASH by independently reducing liver triglyceride and cholesterol levels through different mechanisms [5]. - FGF21 signaling directly acts on glutamatergic neurons in the CNS, stimulating the reduction of liver triglycerides and reversing fibrosis, while also directly signaling liver cells to lower cholesterol levels [6][8]. Group 2 - Mechanistically, FGF21 increases sympathetic nervous activity in the liver, thereby inhibiting de novo lipogenesis [7]. - The core findings of the study include that FGF21 can reverse diet-induced MASH, directly signals the CNS to lower liver triglyceride levels and fibrosis, signals liver cells to reduce cholesterol during MASH, and enhances liver sympathetic nervous activity while decreasing de novo lipogenesis [8]. - Overall, these findings provide a promising drug target and new insights for the treatment of MASH [10].