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

Metabolic Dysfunction-Associated Steatotic Liver Disease: Tips for the Endocrinologist (ENDO 2025) - "This session will explore emerging pharmacological treatments, including incretin-based therapies, FGF21 analogues, and the panPPAR agonist lanifibranor, targeting both MASLD and T2DM-related liver fibrosis. We will also discuss the first FDA-approved treatment targeting the thyroid hormone receptor to promote anti-fibrotic effects without altering insulin resistance. Join us for a clinical update on screening strategies and the latest treatment options for endocrinologists managing MASLD in patients with metabolic disorders."

Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus • FGF21

MTP24. Metabolic Dysfunction-Associated Steatotic Liver Disease: Tips for the Endocrinologist (ENDO 2025) - "This session will explore emerging pharmacological treatments, including incretin-based therapies, FGF21 analogues, and the panPPAR agonist lanifibranor, targeting both MASLD and T2DM-related liver fibrosis. We will also discuss the first FDA-approved treatment targeting the thyroid hormone receptor to promote anti-fibrotic effects without altering insulin resistance. Join us for a clinical update on screening strategies and the latest treatment options for endocrinologists managing MASLD in patients with metabolic disorders."

Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus • FGF21

Inventiva announces the publication in Journal of Hepatology Reports on results of lanifibranor treatment on liver sinusoidal endothelial cells in patients with MASLD/MASH and in preclinical models of the disease (GlobeNewswire) - P2b | N=247 | NATIVE (NCT03008070) | Sponsor: Inventiva Pharma | "The results from the Phase 2b NATIVE trial with lanifibranor show a correlation between LSEC capillarization and both the stage of fibrosis and inflammation, along with evidence suggesting that lanifibranor can reduce this capillarization....The LSEC alteration was evaluated using CD34 staining in the Phase 2b NATIVE biopsies, which showed a higher density of CD34 staining in patients with MASLD or MASH compared to patients without MASLD. The CD34 staining was shown to be associated with liver fibrosis and to a lesser extent with inflammation. CD34 staining on the NATIVE liver biopsies was reduced in a dose-dependent manner following the treatment with lanifibranor for 24 weeks....Two preclinical models for MASLD and MASH showed that vascular modifications appear at early stages of disease development even before inflammation and fibrosis."

P2b data • Preclinical • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Therapeutic horizons in metabolic dysfunction-associated steatohepatitis. (PubMed, J Clin Invest) - "Recent trials with agents such as semaglutide, tirzepatide, survodutide, lanifibranor, pegozafermin, and resmetirom demonstrate substantial promise in resolving MASH and improving fibrosis, but unresolved issues remain regarding treatment duration, response heterogeneity, and long-term adherence. As the field moves toward combination therapies and precision medicine, the definition of therapeutic success will likely evolve to reflect both histological improvement and patient-reported outcomes. This Review provides a timely synthesis of the landscape, challenges, and future directions in MASH therapeutics."

Journal • Review • Diabetes • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • FASN • FGF21 • PNPLA3

Does the benefit of optimal MASH treatment depend on a reduction in myosteatosis? (PubMed, Clin Res Hepatol Gastroenterol) - "The convincing results obtained with a triple peroxisome proliferator-activated receptor (PPAR) agonist in this setting confirm this hypothesis, demonstrating a beneficial effect not only on the severity of MASH in terms of steatosis, inflammation and fibrosis, but also in terms of hepatic and muscle insulin sensitivity. The pathophysiology of MASH and mechanism of action of triple PPAR agonist suggest that this may be related to improved lipid management in skeletal muscles and highlights the importance of studying the muscle-adipose tissue-liver axis in the management of MASH."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Altered liver sinusoidal endothelial cells in MASLD and their evolution following lanifibranor treatment. (PubMed, JHEP Rep) - "Lanifibranor treatment, a pan-peroxisome proliferator-activated receptor agonist currently tested in a phase III clinical trial, improves LSEC capillarisation but also intrahepatic vascular resistance and portal pressure in MASLD. Targeting LSECs appears to be a promising approach to improve MASH."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • CD34

Inventiva secures the €116 million second tranche of its structured financing of up to €348 million (GlobeNewswire) - "Inventiva...announced that the Board of Directors called the second tranche of its previously announced1 structured financing of up to €348 million (the 'Structured Financing'), for gross proceeds of €115.6 million (net proceeds of €108.5 million) (the 'T2 Transaction')....The Company intends to use the net proceeds from the T2 Transaction (€108.5 million), together with existing cash and cash equivalents, mainly to finance lanifibranor’s development in MASH and notably the continuation of its NATiV3 Phase 3 clinical trial."

Financing • Metabolic Dysfunction-Associated Steatohepatitis

Results of LEGEND evaluating lanifibranor in combination with empagliflozin in MASH selected for oral presentation at the upcoming EASL SLD Summit 2025 (GlobeNewswire) - P2 | N=42 | LEGEND (NCT05232071) | Sponsor: Inventiva Pharma | "The abstract evaluates the impact of combining lanifibranor with empagliflozin on metabolic improvements in patients with MASH and type-2 diabetes (T2D)....The study met its primary efficacy endpoint, demonstrating a significant reduction in HbA1c levels in both the lanifibranor arm and the combination arm (lanifibranor with empagliflozin) compared to placebo. Furthermore, therapeutic efficacy with statistical significance was observed across multiple secondary endpoints, including markers of liver injury, glucose and lipid metabolism, and hepatic steatosis. The improvement in cardiometabolic and hepatic markers of MASH was similar in both active treatment groups. Of note, there was no weight gain in patients receiving the combination of lanifibranor and empagliflozin. The treatment with lanifibranor at a dosage of 800mg/once daily alone or in combination with empagliflozin was well tolerated..."

P2 data • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

HK3, a novel oral anti-obesity MASH drug with direct reduction of liver fibrosis (EASL 2025) - "Human hepatic stellate cells (LX2) were treated with TGF-β1 (5 ng/ml, 24h) with HK3 or competitor drugs (semaglutide, lanifibranor and resmetirom, all 10 µM) to assess pro-fibrotic protein levels. This comprehensive study reveals HK3 as a promising candidate for MASH treatment, demonstrating both potent direct anti-fibrotic and anti-obesity effects. Its unique mechanism of action and multi-faceted benefits position HK3 as a potential first-in-class therapy for the concurrent management of MASH and obesity, addressing two critical aspects of metabolic liver disease."

Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • TGFB1

Inventiva announces the publication in Clinical Gastroenterology and Hepatology of its analysis of new biomarker signatures predictive of histological response in patients with MASH treated with lanifibranor (GlobeNewswire) - "Inventiva...announced publication in the peer-reviewed medical journal Clinical Gastroenterology and Hepatology, of its analysis on new non-invasive biomarker signatures predictive of histology response following treatment with lanifibranor in patients with MASH and fibrosis....The biomarker signatures developed for fibrosis improvement, MASH resolution and composite histological endpoints, suggested better predictive accuracy than other diagnostic scores available including FIB4, FIBC3, ABC3D, NFS, ELF and MACK-3. The biomarker signatures suggested strong predictive accuracy, with AUROC values above 0.80 that may indicate high reliability in distinguishing responders from non-responders. The analysis confirmed that histological response to lanifibranor could be assessed with non-invasive signatures based on blood markers."

Biomarker • Metabolic Dysfunction-Associated Steatohepatitis

Inventiva announces completion of enrollment in the Phase 3 NATiV3 clinical trial of lanifibranor in patients with MASH and advanced fibrosis (GlobeNewswire) - "Inventiva...announced the completion of patient enrollment in its NATiV3 Phase 3 clinical trial with the randomization of the last patient in the main cohort. Inventiva has enrolled 1009 patients in the main cohort and 410 patients in the exploratory cohort exceeding the original target of 969 and 350, respectively....Topline results from NATiV3 projected in the second half of 2026 and, if positive, expected to be the basis for submission for regulatory approval."

Enrollment closed • P3 data: top line • Fibrosis • Metabolic Dysfunction-Associated Steatohepatitis

Old and New Classes of Lipid Metabolism and Glucose Control Agents: PAN-PPAR-Agonist (APASL 2025) - "Pan-PPAR agonists represent a paradigm shift in MASH management by simultaneously addressing multiple aspects of disease pathophysiology. With compelling phase 2b data and ongoing phase 3 trials, lanifibranor may become a cornerstone therapy for MASH, though long-term studies are still needed to monitor potential adverse effects such as weight gain, edema, heart failure, and fracture risk."

Cardiovascular • Congestive Heart Failure • Diabetes • Fibrosis • Heart Failure • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Musculoskeletal Diseases • Orthopedics • Portal Hypertension • Type 2 Diabetes Mellitus • FGF21 • PPARA

The pan-PPAR Agonist Lanifibranor Improves Liver Inflammation, Ballooning, and Fibrosis in a Diet-induced Obese MASH Hamster Model of Binge Drinking (APASL 2025) - "While BD only impaired lipid metabolism in healthy hamsters, it worsened hypertriglyceridemia and liver lesions in obese MASH hamsters. LANI significantly improved dyslipidemia and liver lesions in obese MASH hamsters. This preclinical model will help to evaluate drugs targeting MASH in a context of moderate to heavy alcohol use."

Preclinical • Dyslipidemia • Fibrosis • Hepatology • Hypertriglyceridemia • Immunology • Inflammation • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Oncology • ALDH1A1 • CASP3 • COL1A1 • COL3A1 • CYP2E1 • IL1B • IL6 • SREBF1 • TIMP1

Ferrous Sulfide Nanosheet as a Novel Drug Delivery System for Lanifibranor to Ameliorate Liver Fibrosis (APASL 2025) - "In this study, we developed an HSC-specific delivery system (VA-FeS@LA) to improve the therapeutic efficacy of lanifibranor on liver fibrosis. Compared with FeS and lanifibranor, VA-FeS@LA exhibited increased deposition in HSCs and a favorable antifibrotic effect. VA-FeS@LA nanocomposite represents a promising therapeutic approach to the treatment of liver fibrosis."

Addiction (Opioid and Alcohol) • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • COL1A1 • IL1B • IL6 • TNFA

Comparison of Pharmacological Therapies for Metabolic Dysfunction-Associated Steatohepatitis: Systematic Review and Network Meta-analysis (APASL 2025) - "For the co-primary endpoint of fibrosis improvement without MASH resolution, pegozafermin, cilofexor + firsocostat, survodutide, obeticholic acid, tirzepatide, and resmetirom were significantly better than placebo in improving ≥ 1 fibrosis stage without worsening MASH. Pegozafermin (SUCRA: 90.18), cilofexor plus firsocostat (SUCRA: 82.82), and cilofexor plus selonsertib (SUCRA: 79.62) were ranked the most effective interventions. For the co-primary endpoint of MASH resolution without worsening fibrosis, pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, and lanifibranor were significantly better than placebo... This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design."

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

Inventiva reports its 2024 full year results and provides a business update (GlobeNewswire) - "Net cash used in operating activities amounted to (€85.9) million in 2024, compared to (€81.6) million in 2023, an increase of 5.3%. R&D expenses, mainly driven by the development of lanifibranor in MASH, amounted to €90.9 million in 2024 and were down 17% compared to the €110.0 million in 2023. The decrease in R&D expenses over the period is primarily due to the temporary voluntary pause in the recruitment of patients in the NATiV3 Phase 3 clinical trial of lanifibranor in MASH following the Suspected Unexpected Serious Adverse Reaction ('SUSAR') reported in the first quarter of 2024 and, to a lesser extent....For the second half of 2024, R&D expenses started to increase again following the restart of patient recruitment in NATiV3."

Commercial • Metabolic Dysfunction-Associated Steatohepatitis

Biomarkers of histological response in lanifibranor-treated patients with metabolic dysfunction-associated steatohepatitis. (PubMed, Clin Gastroenterol Hepatol) - P2b | "Results from this analysis show evidence that baseline values and changes in selected serum biomarkers can aid in predicting histological response in MASH under lanifibranor treatment. These findings support utilizing a similar approach in a larger sample size (NATiV3, NCT03008070)."

Biomarker • Journal • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • KRT18 • MMP9

Metabolic effects and mechanism of action of the pan PPAR agonist Lanifibranor. (PubMed, J Hepatol) - No abstract available

Journal

Inventiva announces the publication in Biomedicine & Pharmacotherapy of the results from a preclinical study showing improvement of portal hypertension with lanifibranor treatment (GlobeNewswire) - "Inventiva...today announced the publication in Biomedicine & Pharmacotherapy, a peer-reviewed, scientific journal, of the results from a preclinical study demonstrating that lanifibranor may reduce Portal Hypertension ('PH')....Mice in the PPVL and cBDL models received daily treatments of lanifibranor for 7 days and 14 days, respectively, at two doses (10 and 30 mg/kg) to assess the effect of lanifibranor on PH, as measured by portal pressure....'The study’s results highlight the potential of lanifibranor in addressing the challenging issue of portal hypertension, which is a major driver of decompensation in advanced chronic liver disease such as MASH, but also occurs early in MASLD.'"

Preclinical • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Portal Hypertension

Inventiva and Hepalys Pharma, Inc. announce the initiation of the clinical development program of lanifibranor in Japan with the dosing of the first participant in Phase 1 trial (GlobeNewswire) - "Inventiva...and Hepalys Pharma...announced today the initiation of the clinical development program of lanifibranor in Japan with the first Japanese participant dosed in a Phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetics ('PK') and pharmacodynamics ('PD') of lanifibranor. As part of the single-center study, 32 subjects will be separated randomly into four cohorts and will receive lanifibranor once daily for 14 days....Positive results from this trial could support the initiation of a pivotal Phase 3 trial in patients in Japan with MASH..."

Trial status • Metabolic Dysfunction-Associated Steatohepatitis

Inventiva reports preliminary 2024 fiscal year financial results and provides a business update (GlobeNewswire) - "Last patient screened in the NATiV3 Phase 3 clinical trial of lanifibranor in MASH early January 2025 and randomization of the last patient expected within the first half of 2025....R&D expenses, mainly driven by the development of lanifibranor in MASH, amounted to €90.9 million in 2024 and were down 17% compared to the €110.0 million in 2023....Topline results of NATiV3 – expected in the second half of 2026."

Commercial • Enrollment status • Metabolic Dysfunction-Associated Steatohepatitis

Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis. (PubMed, Hepatology) - "This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design."

Journal • Retrospective data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Inventiva announces the publication of the results from the investigator-initiated proof-of-concept clinical trial evaluating lanifibranor in patients with T2D and MASLD in the Journal of Hepatology (GlobeNewswire) - P2 | N=128 | NCT03459079 | "The proof-of-concept trial evaluating lanifibranor (800mg/day for 24 weeks) in 38 patients with MASLD and T2D achieved its primary efficacy endpoint. Patients that received treatment with lanifibranor achieved a 44% reduction in intrahepatic triglycerides (IHTG) measured using proton magnetic resonance spectroscopy (1H-MRS), significantly outperforming the placebo group (12%). The treatment with lanifibranor also resulted in a higher proportion of patients achieving over 30% liver triglyceride reduction (65% vs. 22%) and MASLD resolution (25% vs. 0%). Secondary endpoints showed improvements in glycemic control, lipid profiles, hepatic insulin sensitivity, muscle glucose disposal, and adipose tissue function. Lanifibranor was well tolerated with no safety concerns reported."

P2 data • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

The combination of lanifibranor with empagliflozin further enhances metabolic improvement in patients with metabolic dysfunction-associated steatohepatitis (MASH) and type-2 diabetes (T2D) (EASL-SLD 2025) - "The combination of lanifibranor with an SGLT2 inhibitor is well tolerated and has comparable beneficial effects on noninvasive hepatic and cardiometabolic markers of MASH as lanifibranor monotherapy, including a shift toward SAT, without observed weight gain. The combination is well tolerated.a.g.holleboom@amsterdamumc.nl"

Clinical • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • TIMP1

The pan-PPAR agonist lanifibranor improves liver inflammation, ballooning, and fibrosis in a diet-induced obese MASH hamster model of binge drinking (EASL-SLD 2025) - "LANI significantly improved dyslipidemia and liver lesions in our obese MASH hamster model of binge drinking, which should help evaluating drugs targeting MASH in a context of moderate to heavy alcohol use."

Preclinical • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • CASP3 • COL1A1 • IL1B • IL6 • TIMP1