Five poster presentations showing : the correlation between the improvement of hepatic steatosis and a robust increase in adiponectin levels, improvement in lipid profile and glycemic control in patients with non-cirrhotic NASH treated with lanifibranor.the Early improvement in ALT or AST being predictive of response pattern of liver histology as well as non-invasive hepatic and cardiometabolic biomarkers observed after 24-week treatment with lanifibranor in patients with non-cirrhotic NASH.the improvement of portal hypertension and splanchnic circulation independently of fibrosis reduction and metabolic improvement following lanifibranor treatment in a mouse model of prehepatic portal hypertension.the reduction of the increased portal pressure and improvement of steatosis in a rat model of early NAFLD following a 4-week lanifibranor treatment. the greater reduction of the increased portal pressure associated with early NAFLD following lanifibranor treatment compared to the PPAR agonists α, δ or γ individually.
Daix (France), Long Island City (New York, United States), June 7, 2023 – Inventiva (Euronext Paris and Nasdaq: IVA), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of non-alcoholic steatohepatitis (NASH) and other diseases with significant unmet medical needs, today announced that five abstracts have been selected for poster presentation at the upcoming International Liver Congress™ 2023 hosted by the European Association for the Study of the Liver (EASL) on June 21-24, 2023 in Vienna, Austria.
The first abstract evaluates the correlation between severity and improvement of hepatic steatosis, adiponectin response, and improvement of markers of cardiometabolic health following a 24 weeks treatment with lanifibranor. Based on the results of Inventiva’s NATIVE Phase IIb clinical trial evaluating lanifibranor in NASH, the authors analysed the correlation between the biomarkers of cardiometabolic health and hepatic steatosis, which is a marker of cardiovascular risk, in patients who were randomized to lanifibranor or placebo. The hepatic steatosis was measured by histological grading and by imaging using Controlled Attenuation Parameter (“CAPTM”) Fibroscan®. As previously shown, treatment with lanifibranor improved the hepatic steatosis and the biomarkers of cardiometabolic health, including adiponectin, insulin resistance and markers of lipid and glucose metabolism. In this analysis, these beneficial cardiometabolic effects were shown to be correlated with an improvement in steatosis both measured histologically and using CAP.
The second abstract focuses on the identification of non-invasive tests as potential predictor tools of histological response or non-response to lanifibranor. Based on the data of the NATIVE trial, the authors evaluated the ability early improvements in aminotransferase levels measured after a 4-week treatment with lanifibranor to predict the histological non-responses to treatment evaluated at 24 weeks. The results demonstrated that in patients with NASH treated with lanifibranor, the absence of a 15% reduction in alanine aminotransferase (“ALT”) levels after 4 weeks of treatment was an effective tool to predict non-response on histological NASH resolution. In addition, the early decrease in ALT and aspartate aminotransferase (“AST”) after 4 weeks of treatment with lanifibranor, correlated with an improvement of non-invasive hepatic biomarkers and markers of cardiometabolic health observed after 24 weeks of treatment with lanifibranor.
The third abstract evaluates the effect of lanifibranor on the portal pressure in models of hepatic and prehapetic portal hypertension. Given that portal hypertension (“PHT”) can cause severe complications in patients with advanced chronic liver disease (“ACLD”), the authors evaluated the effect of a daily treatment with lanifibranor on portal hypertension in two mice models of portal hypertension. They demonstrated that lanifibranor reduced the portal pressure independently of fibrosis reduction or of an effect on metabolism, but through the reduction of the venous mesenteric vascular expansion and splanchnic angiogenesis, and an amelioration of the liver sinusoidal endothelial cells.
The fourth abstract evaluates the effect of lanifibranor on portal pressure, endothelial dysfunction and liver histology in a rat model of early NAFLD. The authors demonstrated that in an early NAFLD-induced rat model without inflammation or fibrosis, lanifibranor treatment completely normalized the portal pressure and the trans-hepatic pressure gradient. In addition lanifibranor improved the hyperreactivity to the vasoconstrictor methoxamine and the hyporeactivity to the vasodilator acetylcholine in the NAFLD-induced rat model. In parallel, the authors also demonstrated the reduction of steatosis evaluated histologically, although not sufficient to explain the observed vascular effects.
The fifth abstract compares the effect of each individual PPAR isotopes α, δ and γ to the pan-PPAR lanifibranor on the improvements of the vascular alterations and histology in a NAFLD-induced rat model. The authors demonstrated that in a rat model of early NAFLD with steatosis but no inflammation or fibrosis, treatment with Fenofibrate (PPAR-alpha agonist), GW501516 (PPAR-delta agonist) and Rosiglitazone (PPAR-gamma) decreased the portal pressure and the transhepatic pressure gradient with a limited effect on the hepatic steatosis. The improvements on the vascular function were more pronounced with lanifibranor than with each individual PPAR agonist. These data suggest that there is an additive effect of combined PPAR agonists compared to mono-agonist leading to an greater improvement of the vascular alterations in early NAFLD.
The details of the various presentations are as follows:
Abstract #1: Abstract title:"Correlation between severity of hepatic steatosis and markers of cardiometabolic health, and effect of lanifibranor therapy in patients with non-cirrhotic NASH"Abstract identifier:FRI-517Presentation type:Poster presentationAuthors:Michael P Cooreman, Sven Francque, Philippe Huot-Marchant, Lucile Dzen, Martine Baudin, Jean-Louis Junien, Pierre Broqua, Manal F AbdelmalekDate:June 23, 2023 – 9:00-18:00 (CEST) Abstract #2: Abstract title:"Early aminotransferase improvement in the phase 2b NATIVE study is predictive of response pattern of liver histology as well as hepatic and cardiometabolic health markers at the end of treatment in patients with non-cirrhotic NASH"Abstract identifier:SAT-393Presentation type:Poster presentationAuthors:Quentin M Anstee, Philippe Huot-Marchand, Lucile Dzen, Jean-Louis Junien, Pierre Broqua, Sven Francque, Manal F Abdelmalek, Michael P Cooreman, Stephen A HarrisonDate:June 24, 2023 – 9:00-17:00 (CEST) Abstract #3: Abstract title:"The pan-PPAR agonist lanifibranor decreases portal pressure in models of both hepatic and prehepatic portal hypertension"Abstract identifier:THU-361Presentation type:Poster presentationAuthors: Anneleen Heldens, Christophe Casteleyn, Louis Onghena, Milton Baoheng Antwi, Benedicte Descamps, Christian Vanhove, Xavier Verhelst, Hans Van Vlierberghe, Lindsey Devisscher, Jean-Louis Junien, Anja Geerts, Guillaume Wettstein, Sander LefereDate:June 22, 2023 – 9:00-18:30 (CEST) Abstract #4: Abstract title:"The pan-PPAR agonist Lanifibranor improves increased portal pressure, endothelial dysfunction and liver histology in a rat model of early NAFLD"Abstract identifier:WED-466Presentation type:Poster presentationAuthors: Shivani Chotkoe, Yao Liu, Guillaume Wettstein, Jean-Louis Junien, Luisa Vonghia, Hannah Ceuleers, Joris De Man, Benedicte De Winter, Wilhelmus J. Kwanten, Sven FrancqueDate:June 21, 2023 – 9:00-18:00 (CEST) Abstract #5: Abstract title:"Unraveling the individual contributions of the PPAR isotypes to the pan-PPAR agonist Lanifibranorinduced improvements of the vascular alterations and liver histology in a rat model of early NAFLD"Abstract identifier:WED-523Presentation type:Poster presentationAuthors: Shivani Chotkoe, Yao Liu, Guillaume Wettstein, Jean-Louis Junien, Luisa Vonghia, Hannah Ceuleers, Joris De Man, Benedicte De Winter, Wilhelmus J. Kwanten, Sven FrancqueDate:June 21, 2023 – 9:00-18:00 (CEST) Inventiva will also be present with a booth and we are inviting you to visit us from Wednesday, June 21st until Saturday, June 24th at booth #19 located in the exhibition hall of the conference center.
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 NASH, mucopolysaccharidoses (“MPS”) and other diseases with significant unmet medical need. The Company benefits from a strong expertise and experience in the domain of compounds targeting nuclear receptors, transcription factors and epigenetic modulation. Inventiva is currently advancing one clinical candidate, has a pipeline of two preclinical programs and continues to explore other development opportunities to add to its pipeline.
Inventiva’s lead product candidate, lanifibranor, is currently in a pivotal Phase III clinical trial, NATiV3, for the treatment of adult patients with NASH, a common and progressive chronic liver disease for which there are currently no approved therapies.
Inventiva’s pipeline also includes odiparcil, a drug candidate for the treatment of adult MPS VI patients. As part of Inventiva’s decision to focus clinical efforts on the development of lanifibranor, it suspended its clinical efforts relating to odiparcil and is reviewing available options with respect to its potential further development. Inventiva is also in the process of selecting an oncology development candidate for its Hippo signaling pathway program.
The Company has a scientific team of approximately 90 people with deep expertise in the fields of biology, medicinal and computational chemistry, pharmacokinetics and pharmacology, and clinical development. It owns an extensive library of approximately 240,000 pharmacologically relevant molecules, approximately 60% of which are proprietary, as well as a wholly-owned research and development facility.
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). www.inventivapharma.com
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Attachment
Inventiva - PR - EASL Abstracts - EN - 06 07 2023
