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

• Analysis of liver sinusoidal endothelial cells (“LSEC”) from screening and end of treatment biopsies in the Phase 2b NATIVE study showed evidence of LSEC capillarization in patients without MASH, and a further increased capillarization in patients with MASH
  
  
• In addition, in the subgroup of patients without MASH, there was higher LSEC capillarization in patients with MASLD than those with normal histology
  
  
• LSEC capillarization observed in patients was strongly associated with liver fibrosis and to a lesser extent inflammation
  
  
• End of treatment biopsies from Phase 2b NATIVE showed improvement in LSEC capillarization in patients with MASH and treated with lanifibranor compared to placebo
  
  
• In addition, using two preclinical models, lanifibranor demonstrated effects extending beyond capillarization reversal, normalizing portal pressure and intrahepatic vascular resistance
  
  
• These effects in the preclinical models appear more pronounced than those observed with single PPAR agonists, suggesting that as a pan-PPAR agonist, lanifibranor could represent a comprehensive therapeutic approach for MASH, fibrosis regression, and the prevention of progression to cirrhosis

 Daix (France), New York City (New York, United States), July 2, 2025 – Inventiva (Euronext Paris and Nasdaq: IVA) (“Inventiva” or the “Company”), a clinical-stage biopharmaceutical company focused on the development of oral therapies for the treatment of metabolic dysfunction-associated steatohepatitis (“MASH”), today announces the publication in Journal of Hepatology Reports, a peer-reviewed, scientific journal, of results from the Phase 2b NATIVE clinical trial and preclinical study evaluating the effects of lanifibranor on liver sinusoidal endothelial cells in Metabolic dysfunction-associated steatotic liver disease (“MASLD”) and MASH.

Kris V. Kowdley MD, Director of the Liver Institute Northwest, Washington said: “The liver sinusoidal endothelial cells (LSECs) play a crucial role in the vascular changes seen in liver diseases, including MASH and cirrhosis. Capillarization of these cells appears early, even before the onset of MASH. 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. These findings strengthen our confidence in lanifibranor's potential to help prevent progression to cirrhosis and associated clinical events.”

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. These data suggest that lanifibranor potentially reduces LSEC capillarization, a key driver in the progression of cirrhosis, in patients with MASH and fibrosis.

Two preclinical models for MASLD and MASH showed that vascular modifications appear at early stages of disease development even before inflammation and fibrosis. Moreover, these models showed that the effects of lanifibranor potentially extend beyond capillarization reversal, normalizing intrahepatic vascular resistance (IHVR) demonstrated by normalization of portal vein pressure and the ex-vivo measured transhepatic pressure gradient. These effects were superior to those observed with single PPAR agonists.

LSEC dysfunction is increasingly recognized as a key contributor to the progression of chronic liver diseases. LSEC dysfunction is characterized by loss of fenestrations (defenestration) and by capillarization, which disrupts hepatic microcirculation, leading to impaired substrate exchange, increased intrahepatic vascular resistance, and elevated portal pressure. This dysfunction also promotes a pro-inflammatory and pro-fibrotic environment, facilitating the progression from early-stage liver disease to more advanced conditions such as fibrosis and cirrhosis.

The histological evaluation from the NATIVE Phase 2b trial demonstrated that LSEC capillarization occurs in the very early stage of the disease. We believe the robust dataset from the NATIVE Phase 2b trial combined with the additional data from preclinical models, points to potential benefits of lanifibranor as a pan-PPAR agonist targeting the multiple components of the disease.

Publication details

About lanifibranor

Lanifibranor, Inventiva’s lead product candidate, is an orally available small molecule that acts to induce anti-fibrotic, anti-inflammatory and beneficial vascular and metabolic changes in the body by activating all three peroxisome proliferator-activated receptor (“PPAR”) isoforms, which are well-characterized nuclear receptor proteins that regulate gene expression. Lanifibranor is a PPAR agonist that is designed to target all three PPAR isoforms in a moderately potent manner, with a well-balanced activation of PPARα and PPARδ, and a partial activation of PPARγ. While there are other PPAR agonists that target only one or two PPAR isoforms for activation, lanifibranor is the only pan-PPAR agonist in clinical development for the treatment of MASH. Inventiva believes that lanifibranor’s moderate and balanced pan-PPAR binding profile contributes to the favorable tolerability profile that has been observed in clinical trials and preclinical studies to date. The FDA has granted Breakthrough Therapy and Fast Track designation to lanifibranor for the treatment of MASH.

About Inventiva

Inventiva is a clinical-stage biopharmaceutical company focused on the research and development of oral small molecule therapies for the treatment of patients with MASH. The Company is currently evaluating lanifibranor, a novel pan-PPAR agonist, in the NATiV3 pivotal Phase 3 clinical trial for the treatment of adult patients with MASH, a common and progressive chronic liver disease. 

Inventiva is a public company listed on compartment B of the regulated market of Euronext Paris (ticker: IVA, ISIN: FR0013233012) and on the Nasdaq Global Market in the United States (ticker: IVA). http://www.inventivapharma.com

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• Inventiva - PR - Journal of Hepatology Reports - EN - 07 02 2025

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