PRESS RELEASE




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 capillariza�on in pa�ents without MASH, and a further
increased capillariza�on in pa�ents with MASH

► In addi�on, in the subgroup of pa�ents without MASH, there was higher LSEC capillariza�on in pa�ents
with MASLD than those with normal histology

► LSEC capillariza�on observed in pa�ents was strongly associated with liver fibrosis and to a lesser extent
inflamma�on

► End of treatment biopsies from Phase 2b NATIVE showed improvement in LSEC capillariza�on in pa�ents
with MASH and treated with lanifibranor compared to placebo

► In addi�on, using two preclinical models, lanifibranor demonstrated effects extending beyond
capillariza�on reversal, normalizing portal pressure and intrahepa�c vascular resistance

► These effects in the preclinical models appear more pronounced than those observed with single PPAR
agonists, sugges�ng that as a pan-PPAR agonist, lanifibranor could represent a comprehensive
therapeu�c approach for MASH, fibrosis regression, and the preven�on 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.



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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

Publication title: “Altered liver sinusoidal endothelial cells in MASLD and their evolution following
lanifibranor treatment.”
Authors: Pierre-Emmanuel Rautou, Shivani Chotkoe, Louise Biquard, Guillaume Wettstein,
Denise Van der Graaff, Yao Liu, Joris De Man, Christophe Casteleyn, Sofie Thys, Winnok
H. De Vos, Pierre Bedossa, Michael P. Cooreman, Martine Baudin, Jean-Louis Abitbol,
Philippe Huot-Marchand, Lucile Dzen, Miguel Albuquerque, Pierre Broqua, Jean-Louis
Junien, Luisa Vonghia, Manal F. Abdelmalek, Wilhelmus J. Kwanten, Valérie Paradis,
Sven M. Francque
Online version: https://doi.org/10.1016/j.jhepr.2025.101366


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.




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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

Contacts

Inventiva Brunswick Group ICR Healthcare
Pascaline Clerc Tristan Roquet Montegon / Patricia L. Bank
EVP, Strategy and Corporate Affairs Aude Lepreux / Investor relations
media@inventivapharma.com Julia Cailleteau patti.bank@icrhealthcare.com
+1 202 499 8937 Media relations +1 415 513 1284
inventiva@brunswickgroup.com
+33 1 53 96 83 83


Important Notice

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approval, Inventiva cannot provide assurance on the impacts of the Suspected Unexpected Serious Adverse
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PRESS RELEASE



Reaction on the results or timing of the NATiV3 trial or regulatory matters with respect thereto, that Inventiva is a
clinical-stage company with no approved products and no historical product revenues, Inventiva has incurred
significant losses since inception, Inventiva has a limited operating history and has never generated any revenue
from product sales, Inventiva will require additional capital to finance its operations, in the absence of which,
Inventiva may be required to significantly curtail, delay or discontinue one or more of its research or development
programs or be unable to expand its operations or otherwise capitalize on its business opportunities and may be
unable to continue as a going concern, Inventiva’s ability to obtain financing and to enter into potential
transactions, Inventiva's future success is dependent on the successful clinical development, regulatory approval
and subsequent commercialization of its product candidate, lanifibranor, preclinical studies or earlier clinical trials
are not necessarily predictive of future results and the results of Inventiva's and its partners’ clinical trials may not
support Inventiva's and its partners’ product candidate claims, Inventiva's expectations with respect to its clinical
trials may prove to be wrong and regulatory authorities may require additional holds and/or additional
amendments to Inventiva’s clinical trials, Inventiva’s expectations with respect to the clinical development plan for
lanifibranor for the treatment of MASH may not be realized and may not support the approval of a New Drug
Application, Inventiva’s ability to identify additional products or product candidates with significant commercial
potential, Inventiva’s expectations with respect to its pipeline prioritization plan and related workforce reduction,
including potential benefits, expenses and consequences relating thereto, Inventiva’s ability to execute on its
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entered into in connection with such partnerships, the benefits of its existing and future partnerships on the clinical
development, regulatory approvals and, if approved, commercialization of its product candidates, and the
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Please refer to the Universal Registration Document for the year ended December 31, 2024 filed with the Autorité
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statements referred to above. Consequently, Inventiva accepts no liability for any consequences arising from the
use of any of the above statements


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