lanifibranor (IVA337) / Inventiva, Sino Biopharm, Hepalys Pharma - LARVOL DELTA

Comparative Efficacy and Safety of FGF21 Analogues in MASH: Which Agents Are Advancing and Why? (ACG 2026) - "Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of progressive liver fibrosis and cirrhosis... A structured literature review of PubMed/MEDLINE was conducted through April 2026 using keywords and MeSH terms including âMASH,â âNASH,â âfibroblast growth factor 21,â âFGF21 analogues,â âefruxifermin,â âpegozafermin,â âefimosfermin,â âpegbelfermin,â âresmetirom,â âsemaglutide,â âtirzepatide,â âsurvodutide,â âlanifibranor,â and âclinical trial.â Included studies were randomized controlled trials in biopsy-confirmed MASH or MASLD reporting histologic data...Trials of pegbelfermin and MK-3655 did not meet primary endpoints... Twelve trials (N=3,640) were included. Among FGF21 analogues, efruxifermin 50 mg showed the greatest response, with fibrosis improvement up to 75% and MASH resolution up to 62%..."

Clinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21

Comparative Efficacy and Safety of Incretin-Based Therapies, FGF21 Analogs, and Pan-PPAR Agonists for MASH: A Systematic Review and Bayesian Network Meta-Analysis (ACG 2026) - "Introduction: Metabolic dysfunctionâassociated steatohepatitis (MASH) is an increasing global health burden with limited approved therapies... A total of 14 RCT's comprising 8,462 patients were included, with 53.1% males and 46.9% females. Patients received semaglutide (n=1,642), tirzepatide (n=1,128), survodutide (n=612), retatrutide (n=318), efruxifermin (n=742), pegozafermin (n=512), lanifibranor (n=247), resmetirom (n=2,955), or placebo/standard therapy (n=306). Baseline age, BMI, diabetes prevalence, ALT, and fibrosis stages were comparable."

Retrospective data • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

MASLD: Established Knowledge and Emerging Directions - Guideline Updates. (PubMed, Z Gastroenterol) - "Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health challenge, largely driven by the increasing prevalence of obesity and type 2 diabetes mellitus...Promising clinical data have been reported for resmetirom, semaglutide, tirzepatide, survodutide, lanifibranor, and fibroblast growth factor-21 analogues including efruxifermin, pegozafermin, and efimosfermin.This review summarises current and emerging diagnostic and therapeutic strategies and provides practical guidance for clinical management. In addition, a structured treatment algorithm for non-cirrhotic MASLD (F0-F3), restricted to therapies currently available in Europe and stratified according to diabetes status and fibrosis stage, is proposed as an evidence-based tool for routine clinical practice."

Journal • Review • Cardiovascular • Diabetes • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • FGF21

A new era in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD): clinical breakthroughs and challenges. (PubMed, Front Pharmacol) - "Metabolic dysfunction-associated steatotic liver disease (MASLD), affecting nearly one-third of adults worldwide, encompasses a spectrum from steatosis to steatohepatitis (MASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma, with fibrosis stage as the primary determinant of liver-related outcomes and cardiovascular disease as the leading cause of mortality. The period 2024-2026 has marked a transformative shift, with resmetirom (thyroid hormone receptor-β agonist) gaining accelerated approval in 2024 as the first agent to meet histologic endpoints in MASH, followed by semaglutide (GLP-1 receptor agonist) in 2025, both demonstrating substantial MASH resolution and fibrosis improvement in phase 3 trials; a diverse pipeline, including tirzepatide, efruxifermin, lanifibranor, denifanstat, and dual-incretin agonists, has yielded promising histologic and metabolic outcomes, with several advancing to phase 3 and updated guidelines endorsing pharmacotherapy for..."

Journal • Cardiovascular • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor

Combination pharmacotherapy for MASH: Potential synergistic approaches. (PubMed, Biochem Pharmacol) - "The recent conditional approval of two monotherapies targeting metabolic pathways, the thyroid hormone receptor beta agonist (THRβ) resmetirom and the glucagon-like peptide 1 receptor agonist (GLP1 RA) semaglutide, is kickstarting the therapeutic armamentarium for MASH. Other promising monotherapies may follow in the near future, in particular fibroblast growth factor 21 (FGF21) analogues and pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist lanifibranor...In addition, we highlight the unmet need for effective antifibrotic therapies and discuss future directions for combination therapy in MASH. Based on the available data, we provide recommendations for the most promising combination strategies."

Journal • Review • Diabetes • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • FGF21

Engineered Nanoplatforms Targeting Activated Hepatic Stellate Cells for Liver Fibrosis Therapy via TGF-β Axis Inhibition and Ferroptosis Induction. (PubMed, Adv Healthc Mater) - "Lanifibranor, a pan-peroxisome proliferator-activated receptor agonist, has shown promising antifibrotic efficacy; however, its clinical application is limited by rapid systemic clearance and insufficient accumulation in fibrotic liver tissue...Mechanistically, the therapeutic efficacy of FVL arises from a dual-action mechanism: inhibition of SMAD2/3 phosphorylation within the transforming growth factor-β (TGF-β) signaling pathway and induction of ferroptosis in aHSCs. In conclusion, this study provides an effective aHSC-specific nanotherapeutic strategy for liver fibrosis treatment and highlights the translational potential of FVL nanoplatforms for targeted antifibrotic therapy."

Journal • Fibrosis • Immunology • Liver Cirrhosis • TGFB1

Inventiva to Present Multiple Abstracts at Paris MASH 2026 (GlobeNewswire) - "Clinical data from Phase 1 and Phase 2 trials demonstrated direct PPAR target engagement, as reflected by increases in adiponectin, together with improvements observed in measures of insulin sensitivity, glycemic control, lipid parameters, and selected cardiovascular risk factors, with effects observed in patients with or without Type 2 diabetes. Separate preclinical studies demonstrated improvement in hepatic and metabolic parameters, and further characterized lanifibranor’s balanced pan-PPAR pharmacology, supporting a differentiated fluid and cardiac profile within the PPAR class."

Clinical data • Preclinical • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Pan-PPAR agonists: emerging therapeutic strategies for metabolic dysfunction-associated steatotic liver disease. (PubMed, Metabolism) - "While selective or dual PPAR agonists have reached efficacy plateaus and raised safety concerns in clinical trials, pan-PPAR agonists coordinated activation of all three PPAR isoforms with broader therapeutic efficacy and improved safety profiles. This review delineates the biological rationale for PPAR modulation in MASLD, critically evaluates current preclinical and clinical evidence for pan-PPAR agonists, and discusses emerging strategies for optimizing their development as comprehensive therapeutic interventions for MASLD."

Journal • Review • Hepatocellular Cancer • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor

Inventiva…announced the last patient has completed their final 72-week visit in the NATiV3 Phase 3 clinical trial evaluating lanifibranor for the treatment of patients with MASH with moderate and advanced fibrosis (GlobeNewswire) - "NATiV3 enrolled 1,009 adults with biopsy-proven non-cirrhotic MASH and F2/F3 fibrosis, with an additional 410 patients enrolled in an exploratory cohort. With the last patient having completed their final visit, all patients have completed the 72-week treatment period. Inventiva expects to report topline results from NATiV3 in the fourth quarter of 2026, as previously communicated. If the results are favorable, the Company anticipates regulatory submission in the first half of 2027 and is preparing for a potential U.S. launch of lanifibranor in 2028, subject to FDA approval."

FDA filing • Launch US • P3 data: top line • Trial status • Metabolic Dysfunction-Associated Steatohepatitis

Pan-peroxisome proliferator-activated receptor agonist IVA337 alleviates secondary lymphedema via inhibiting TGFβ/SMAD2/3 signaling pathway. (PubMed, Vascul Pharmacol) - "Collectively, our findings demonstrate that IVA337 protects against early-stage lymphedema by suppressing TGFβ/SMAD2/3 signaling and limiting inflammatory and fibrotic and lymphatic endothelial dysfunction. These findings identify pan-PPAR activation as a promising pharmacological strategy to preserve lymphatic function during the early phase of lymphedema and potentially prevent progressive tissue fibrosis."

Journal • Fibrosis • Immunology • Inflammation • Metabolic Disorders • CDH5 • CLDN5 • PPARA

Pan-Peroxisome Proliferator-Activated Receptor Agonist IVA337 Alleviates Secondary Lymphedema via Inhibiting TGFβ/SMAD2/3 Signaling Pathway. (PubMed, bioRxiv) - "Collectively, our findings demonstrate that IVA337 protects against early stage lymphedema by inhibiting TGFβ/SMAD2/3-mediated inflammatory and fibrotic responses. This study provides a potential therapeutic strategy to improve lymphatic function during the early phase of lymphedema and prevent progressive fibrosis in patients with lymphedema and related disorders."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • CDH5 • CLDN5

Inventiva Announces Completion of the EIB Warrant Restructuring with the Issuance of New EIB Warrants (Yahoo Finance UK) - "Inventiva...is pleased to announce the completion of the final step of the transactions previously announced on June 2, 2026 (the 'Combined Transaction') through the issuance of approximately 15.7 million new warrants (bons de souscription d'actions) (the 'New EIB Warrants') to the European Investment Bank (the 'EIB') and the surrender and cancellation of all remaining warrants originally issued to the EIB in January 2024 (the "Legacy EIB Tranche B Warrants") that were not repurchased in the Combined Transaction...This achievement, together with the previously announced broader refinancing, provides Inventiva with increased financial flexibility as we continue advancing the development of lanifibranor, our investigational pan-PPAR agonist for the treatment of MASH."

Commercial • Metabolic Dysfunction-Associated Steatohepatitis

From dual to quintuple agonism for next-generation pharmacology to treat obesity and type 2 diabetes: synergistic incretin and nuclear receptor signaling. (PubMed, Cardiovasc Diabetol Endocrinol Rep) - "Unlike unconjugated lanifibranor, the conjugate did not induce anemia, fluid retention, renal dysfunction, or adipocyte differentiation, supporting the concept that tissue-restricted PPAR activation may mitigate classical adverse effects of systemic PPAR agonism. These findings establish peptide-directed nuclear receptor targeting as a potentially important platform for next-generation metabolic therapeutics, although substantial translational uncertainties remain regarding clinical efficacy, safety, and long-term applicability."

Journal • Diabetes • Genetic Disorders • Hematological Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus

Ultrastructural assessment of liver sinusoidal endothelial cell capillarisation in metabolic-dysfunction associated steatotic liver disease and its modulation by lanifibranor (EASL 2026) - "Across species, LSEC capillarisation develops early in MASLD, albeit heterogeneously, and progresses with disease severity. Lanifibranor restores LSEC (ultra)structure in early MASLD, highlighting its therapeutic potential to restore vascular alterations and beneficially influence disease progression."

Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • CD34

Lanifibranor-induced improvements in histological parameters and cardiometabolic markers in MASH are independent of weight change and closely associated with adiponectin induction (EASL 2026) - "Unlike life-style related weight gain, lanifibranor associated weight gain correlates with increases in ADP and improvements in liver histology. ADP may serve as a biomarker of therapeutic response with lanifibranor. The association between ADP induction and markers of CMH supports improved adipose- tissue health and insulin sensitivity as key mechanisms underlying lanifibranor efficacy in MASH."

Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Anticipated Potential Key Milestones (GlobeNewswire) - "Topline results of NATiV3 – expected in the fourth quarter of 2026."

P3 data: top line • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 ) (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Inventiva Pharma | Trial completion date: Jun 2027 ➔ Sep 2027 | Trial primary completion date: Jun 2027 ➔ Sep 2027

Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 ) (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Inventiva Pharma | Trial completion date: Dec 2026 ➔ Jun 2027 | Trial primary completion date: Dec 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Inventiva to Present Abstracts at the EASL Congress 2026 (GlobeNewswire)

Clinical data • Metabolic Dysfunction-Associated Steatohepatitis

A novel incretin-based quintuple Polyagonist for the Treatment of Obesity and Diabetes (ECO 2026) - "Drugs to improve obesity-linked metabolic dysfunction are on the rise, with GLP-1R:GIPR co-agonism being effective in the management of obesity and type 2 diabetes1,2, and with Lanifibranor (Lani), a nuclear acting small molecule triagonist at the peroxisome proliferator-activated receptors alpha, gamma and delta (PPARα,γ,δ) being in clinical phase 3 for the treatment of metabolic dysfunction-associated steatohepatitis (MASH)3...In vivo, however, the molecule outperforms GLP-1R:GIPR co-agonism and semaglutide to further decrease body weight, food intake, and hyperglycemia in obese and insulin resistant mice through synergistic incretin and PPAR action. The metabolic action of GLP-1:GIP:Lani is blunted in mice with genetic or pharmacological inhibition of GLP-1R, GIPR or PPARδ and is absent in DIO double-incretin receptor knock-out mice, collectively suggesting that GLP-1:GIP:Lani holds unprecedented therapeutic value to treat obesity and diabetes."

Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Type 2 Diabetes Mellitus • PPARA

GLP-1R-GIPR-PPARα/γ/δ quintuple agonism corrects obesity and diabetes in mice. (PubMed, Nature) - "In vivo, however, GLP-1-GIP-lanifibranor outperforms GLP-1R-GIPR co-agonism and semaglutide, further decreasing body weight, food intake and hyperglycaemia in obese and insulin-resistant mice through synergistic incretin and PPAR action. The metabolic action of GLP-1-GIP-lanifibranor is blunted in mice with genetic or pharmacological inhibition of GLP-1R, GIPR or PPARδ and is absent in DIO double incretin receptor-knockout mice, collectively suggesting that GLP-1-GIP-lanifibranor has substantial therapeutic value in the treatment of obesity and diabetes."

Journal • Preclinical • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Type 2 Diabetes Mellitus • PPARA • PPARG

Efficacy of tirzepatide, lanifibranor, and resmetirom in metabolic dysfunction-associated steatotic liver disease: a meta-analysis of high-quality randomized controlled trials. (PubMed, Intern Emerg Med) - P2, P3 | "Gastrointestinal adverse events were common, which may affect tolerability. Due to the limited number of trials for tirzepatide and lanifibranor, further large-scale studies are warranted to confirm their role in MASLD/MASH management."

Journal • Retrospective data • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

An Extravascular Synergistic Cocktail Therapeutic Strategy Based on Lanifibranor Loaded Self-Healing Bioelastomer for Abdominal Aortic Aneurysms. (PubMed, Adv Mater) - "In both the rat and dog AAA models, it has been fully demonstrated that the ESC therapy can provide effective mechanical support to prevent vascular dilation while continuously releasing lanifibranor to regulate myogenic transformation of AFs to inhibit the development of AAA. Additionally, we investigated the feasibility of minimally invasive laparoscopic implantation in bama pigs, emphasizing its potential for clinical translation and application."

Journal • Cardiovascular • Metabolic Disorders • CCL2

Key financial results for the full year of 2025 (GlobeNewswire) - "Net cash used in operating activities amounted to (€104.9) million in 2025, compared to (€85.9) million in 2024, representing an increase of 22%. R&D expenses, mainly related to the development of lanifibranor in MASH, amounted to €87.0 million in 2025, down by 4% from €90.9 million in 2024....R&D expenses for the fiscal year ended December 31, 2025, amounted to (€87.0) million compared to (€90.9) million in 2024. This 4% decrease was primarily due to the focus on the development of lanifibranor in MASH..."

Commercial • Metabolic Dysfunction-Associated Steatohepatitis

Topline results of NATiV3 Phase 3 clinical trial expected for the fourth quarter of 2026 (GlobeNewswire)

P3 data: top line • Metabolic Dysfunction-Associated Steatohepatitis