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

Close multilevel links between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes mellitus. (PubMed, Metabol Open) - "Several pharmacological agents including incretin-based strategies, FGF21 analogues and the panPPAR agonist lanifibranor target the interface of MASLD and T2DM and have thereby shown promise to improve MASH and associated liver fibrosis. In light of the evident close multilevel links between MASLD and T2DM, care development efforts for MASLD in guidelines, local protocols and implementation strategies should aim to involve hepatologists, diabetologists, PCPs and their affiliated care teams in a joint effort to address the growing burden of fibrotic MASLD."

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

Inventiva Announces the Implementation of a New ATM Program (GlobeNewswire) - "Each ADS represents one ordinary share of Inventiva, for aggregate gross sales proceeds of up to $100 million....The Company currently intends to use the net proceeds, if any, of sales of ADSs issued under the program to finance the research and development of lanifibranor, working capital requirements and general corporate purposes."

Financing • Idiopathic Pulmonary Fibrosis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Systemic Sclerosis

TARGETING NUCLEAR PROTEIN IMPROVES NAFLD ACTIVITY SCORE AND SHOWS ANTIFIBROTIC AND HEPATOPROTECTIVE EFFECTS SUPERIOR TO LANIFIBRANOR IN THE GAN DIET-INDUCED OBESE AND BIOPSY-CONFIRMED MOUSE MODEL OF MASH (AASLD 2025) - "NLT-101 treatment improved metabolic, biochemical and histopathological parameters of MASH, including hepatic transcriptomic profile, in the GAN DIO-MASH mouse model. Notably, NLT-101 treatment dose-dependently improved NAFLD Activity Score superior to late-stage clinical candidate lanifibranor, introducing NLT-101 as a promising first-in-class treatment for MASH."

Biopsy • Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • COL1A1

CONTINUOUS DIGITAL PATHOLOGY SCORING REVEALS FIBROSIS REVERSAL AND TREATMENT BENEFIT OF LANIFIBRANOR: INSIGHTS FROM A PRECLINICAL RODENT MODEL. (AASLD 2025) - P2b | "Lanifibranor demonstrated antifibrotic activity in preclinical therapeutic models. High-resolution single-fiber digital pathology (Ph-FCS) offers a more sensitive and continuous assessment of fibrosis regression than traditional methods. These findings support Ph-FCS as a translational biomarker and further support lanifibranor's efficacy as an antifibrotic agent."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • PPARA

HIGH-RESOLUTION DIGITAL PATHOLOGY DEMONSTRATES ANTIFIBROTIC AND ANTI-INFLAMMATORY EFFECTS OF LANIFIBRANOR IN THERAPEUTIC INTERVENTIONS USING TAA-INDUCED CIRRHOTIC RODENT MODELS. (AASLD 2025) - "Lanifibranor showed strong antifibrotic and anti-inflammatory activity in a therapeutic cirrhosis model. Digital pathology biomarkers, including Ph-FCS and cellular panels, provided continuous, high-resolution metrics that outperform traditional readouts. These findings position digital pathology as a powerful translational tool to quantify therapeutic response and advance antifibrotic drug development."

Preclinical • Fibrosis • Gastroenterology • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • PPARA

COMBINING DIGITAL PATHOLOGY AND BIOMARKERS OFFER A TRANSLATIONAL FRAMEWORK TO QUANTIFY FIBROSIS AND LANIFIBRANOR TREATMENT RESPONSE IN A TAA-INDUCED CIRRHOSIS MODEL. (AASLD 2025) - P2b | "Continuous quantitative digital pathology biomarkers can be integrated with complementary molecular or functional biomarkers to provide a multifaceted view of treatment response. While this study demonstrates feasibility, further validation is needed. Differences in response kinetics and biological variability may affect the sensitivity of each modality."

Biomarker • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • COL1A1

Inventiva to Present Multiple Abstracts at AASLD The Liver Meeting 2025 (GlobeNewswire) - "Presentation of a comparison between digital and glass slide histology from screening biopsies in the Phase 3 NATiV3 study. Presentation of digital pathology data from preclinical studies with lanifibranor."

Clinical data • Preclinical • Metabolic Dysfunction-Associated Steatohepatitis

Inventiva reports its unaudited 2025 first-half financial results and provides a corporate update (GlobeNewswire) - "Cash and cash equivalents at €146.7 million including €24.6 million in short-term deposits as of June 30, 2025; Receipt of the gross proceeds of €115.6 million from the second tranche of the structured financing of up to €348 million, following in particular the completion in April 2025 of enrolment of the Phase 3 clinical trial NATiV3 evaluating lanifibranor in patients with MASH; Topline results of NATiV3 are expected in the second half of 2026"

Commercial • P3 data: top line • Metabolic Dysfunction-Associated Steatohepatitis

Inventiva to Host Analyst and Investor Event on October 8, 2025 (GlobeNewswire) - "Agenda topics will include:...(i) A deep dive into lanifibranor’s mechanism of action and clinical evidence to date, including key findings from the Phase 2b trial; (ii) The design and objectives of the ongoing Phase 3 study as well as a progress update and overview of patient baseline characteristics."

P2b data • Trial status • Metabolic Dysfunction-Associated Steatohepatitis

Pathogenesis and Treatment of Non-alcoholic Steatohepatitis and Its Fibrosis: A Systematic Review. (PubMed, Cureus) - "GLP-1 agonists and resmetirom (a THR-β agonist) demonstrated substantial reductions in liver fat content, while lanifibranor (a pan-PPAR agonist) also significantly improved fibrosis. Bariatric surgery showed MASH resolution in 56-70% of cases, though challenges remain regarding incomplete fibrosis reversal and the lack of long-term outcome data. Future research should prioritize combination therapies, explore novel antifibrotic agents, and investigate genetically based therapeutic strategies to better address the multifactorial nature of MASH."

Journal • Review • Critical care • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Treatment Landscape of Metabolic-Dysfunction-Associated Steatotic Liver Disease. (PubMed, J Clin Med) - "Although weight loss, diet, and exercise play a major role, certain therapies including GLP-1 receptor agonists, resmetirom, lanifibranor, and FGF-3 analogs are showing promise when treating patients with MASLD. Several phase 3 trials have revealed promising data when it comes to improving liver fibrosis and histology. This shift in treatment will provide new hope for patients and clinicians when treating this challenging disease."

Journal • Review • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF • FGF3

Antidepressant-like actions of lanifibranor and its related mechanisms in mouse models of depression: Involvement of hippocampal PPARα and BDNF. (PubMed, Biomed Pharmacother) - "The use of two pharmacological inhibitors of PPARα and the BDNF system (GW6471 and K252a), adeno-associated virus (AAV)-PPARα-short hairpin RNA (shRNA), and AAV-BDNF-shRNA fully blocked the antidepressant-like actions of lanifibranor in mouse models. Taken together, the results of this study confirm that lanifibranor may be developed as a new antidepressant in the future."

Journal • Preclinical • CNS Disorders • Depression • Mood Disorders • Psychiatry • BDNF • PPARA

Nanomedicines in the Treatment of Liver Fibrosis: A Review. (PubMed, Int J Nanomedicine) - "For example, lanifibranor and efruxifermin have shown promise in clinical trials. This review explores the pathological mechanisms of liver fibrosis, the current state of clinical treatments, and the application of nanomedicine in the diagnosis and treatment of liver fibrosis. It also discusses the challenges in translating nanomedicines from laboratory research to clinical application and suggests potential improvements, aiming to enhance the understanding of liver fibrosis and provide new insights and approaches for its reversal and potential cure."

Journal • Review • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Safety Choice Drivers of the Coming Treatment Options for Non-Cirrhotic Metabolic Steatohepatitis. (PubMed, Liver Int) - "In this scenario, the Food and Drug Administration's conditional approval of the liver-directed thyroid hormone receptor beta agonist Resmetirom as the first pharmacological treatment for MASH last March 2024 and the expected extension of the glucagon-like protein-1 receptor agonist Semaglutide indication from diabetes and obesity to MASH mark a key milestone...To investigate future trajectories and possible uses as mono-therapy or in combination, we examined available results of clinical trials and real-life studies. Despite the need to await the final results of outcome studies to exclude any possible challenges for both compounds, safety profiles and external factors including reimbursement policies or supply limitations may currently guide the individual choice."

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

Inventiva Reports Preliminary 2025 First-Half Financial Information (GlobeNewswire) - "The Company will need to raise additional funds to achieve its long-term objectives for the development and potential commercialization of lanifibranor through other potential public offerings or private placements and potential strategic options such as business development partnerships, merger and acquisition transactions and/or licensing agreements....The revenues recorded by the Company in the first half of 2025 consist mainly of the $10 million (net proceeds of €8.6 million) milestone payment invoiced to CTTQ and the $5 million (€4.3 million) credit notes recognized under the license agreement with CTTQ following the closing of the second tranche of the Structured Financing in May 2025.As mentioned above, the receipt of the $10 million (gross proceeds) milestone payment from CTTQ in July 2025 will impact the cash flow of the second semester of 2025."

Commercial • Metabolic Dysfunction-Associated Steatotic Liver Disease

Peroxisome Proliferator-activated Receptor Agonist IVA337 Alleviates Inflammation and Fibrosis in MASH by Restoring Lipid Homeostasis. (PubMed, Am J Pathol) - "Additionally, IVA337 modulated multiple signaling pathways, including IL-17, TNF, NF-kappa B, PI3K-AKT, and MAPK. Collectively, these findings demonstrate that IVA337 effectively mitigates fibrosis development in both 2D and 3D MASH models by restoring lipid homeostasis and regulating crucial fibrotic and inflammatory pathways."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • COL1A1 • IL17A • IL6

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

Lanifibranor and semaglutide demonstrate multiple metabolic benefits in free-choice diet induced obese hamster models of MASH and MetALD. (PubMed, Eur J Pharmacol) - "As observed in humans, lanifibranor and semaglutide showed multiple metabolic benefits in free-choice diet induced obese hamster models of MASH and MetALD. These hamster models demonstrated good translability regarding the effects observed in clinical trials and will be helpful to evaluate novel therapies targeting obesity and associated comorbidities, including MetALD."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Dyslipidemia • Genetic Disorders • Heart Failure • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

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

Inventiva receives $10 million milestone payment from CTTQ (GlobeNewswire) - "Inventiva...announced the receipt of a $10 million milestone payment from Chia Tai-Tianqing Pharmaceutical Group Co., Ltd ('CTTQ'), a subsidiary of Sino Biopharm. This milestone payment follows the successful settlement of the second tranche of €115.6 million in gross proceeds (net proceeds of €108.5 million) of the previously announced structured financing of up to €348 million2 (the 'Structured Financing'). In September 2022, Inventiva entered into a licensing and collaboration agreement with CTTQ (as amended on October 11, 2024, the 'CTTQ License Agreement') to develop and commercialize lanifibranor, Inventiva’s proprietary compound, for the treatment of MASH...Under the CTTQ License Agreement, Inventiva is eligible to receive up to an additional $265 million of clinical, regulatory and commercial milestone payments, as well as royalties in the low single digits on annual net sales of lanifibranor, if approved."

Financing • Metabolic Dysfunction-Associated Steatohepatitis

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

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