15/11/2024 22:00
Inventiva will present data from the final analysis of the Phase 2 study evaluating the combination of lanifibranor with empagliflozin in patients with MASH and T2D at the AASLD The Liver Meeting® late-breaker session
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INFORMATION REGLEMENTEE

PRESS RELEASE




Inventiva will present data from the final analysis of the
Phase 2 study evaluating the combination of lanifibranor
with empagliflozin in patients with MASH and T2D at the
AASLD The Liver Meeting® late-breaker session
► Data will be presented on Monday, November 18th as a late breaker poster at the
American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®
2024 in San Diego.

► LEGEND achieved its primary efficacy endpoint by significantly lowering HbA1c
level in both the lanifibranor arm and in the lanifibranor with empagliflozin arm
compared to placebo.

► 50% percent of patients saw their HbA1c levels below 6.5% at week 24 following
treatment with lanifibranor alone or in combination with empagliflozin.

► 58% of patients on lanifibranor alone and 80% of those on the combination therapy
had a decrease of at least 1% in HbA1c at week 24, compared to 0% in the placebo
group.

► Liver function tests, markers of liver fibrosis and markers or cardiometabolic health
including HOMA-IR, hsCRP, ferritin, lipid profile and adiponectin levels were also
improved with lanifibranor alone or in combination with empagliflozin.

► The weight gain observed in a proportion of patients under lanifibranor was not
observed in patients treated with the combination of lanifibranor with
empagliflozin.


Daix (France), Long Island City (New York, United States), November 15, 2024 – Inventiva (Euronext Paris and
Nasdaq: IVA), a clinical-stage biopharmaceutical company focused on the development of oral small molecule
therapies for the treatment of metabolic dysfunction-associated steatohepatitis (“MASH”), also known as non-
alcoholic steatohepatitis (“NASH”), and other diseases with significant unmet medical needs, today announced
the presentation of the final analysis of LEGEND, Phase 2 proof-of-concept clinical trial, evaluating lanifibranor in
combination with empagliflozin in patients with MASH and Type 2 Diabetes (T2D). The data will be presented
Monday November 18, 2024, as a late breaker poster at the American Association for the Study of Liver Diseases
(AASLD) The Liver Meeting®, taking place in San Diego California.

Dr. Michael Cooreman, Chief Medical Officer of Inventiva, stated: “We are pleased to present the results of our
LEGEND study at The Liver Meeting. We believe that the results on the combination of lanifibranor with
empagliflozin not only confirm the benefits of lanifibranor as a monotherapy for patients with MASH and type 2
diabetes but also support a treatment paradigm for combination therapy for this patient population.”

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Dr. Nezam (“Nid”) Afdhal, Chief of Gastroenterology, Beth Israel Deaconess Medical Center, Professor of
Medicine, Harvard Medical School, said: “It is frequently overlooked that MASH is a liver manifestation of insulin
resistance. The exciting new data from the LEGEND study, which evaluates the combination of lanifibranor and
empagliflozin, confirms that lanifibranor has the potential to target the underlying biology of the disease.
Additionally, LEGEND should alleviate the concerns about weight gain, as this can be managed with sGLT2
inhibitors or other treatments like GLP-1 agonists, which are treatments of choice for T2D management.”

The Phase 2, LEGEND, included patients with MASH and T2D with a Hemoglobin A1c (HbA1c) between 7-10% at
screening. The trial was double-blind for lanifibranor and placebo, but open-label for the combination of
lanifibranor and empagliflozin.

The study met the primary efficacy endpoint of HbA1c improvement with both treatment groups and patients
treated with lanifibranor-only and in combination with empagliflozin showed a significant reduction in their HbA1c
levels, with 50% of patients reaching an HbA1c under 6.5% by week 24 (p<0.001). Additionally, 58% of patients
on lanifibranor alone and 80% of those on the combination therapy had a decrease of at least 1% in HbA1c at
week 24, compared to 0% in the placebo group.

In addition, patients treated with lanifibranor alone and in combination with empagliflozin showed significant
improvement in hepatic steatosis, -49% and -41% respectively, measured by Magnetic resonance imaging-proton
density fat fraction (MRI-PDFF), as well as the composite MASH activity and fibrosis measured with cT1, -86 and -
75 ms respectively.

Furthermore, adiponectin levels increased by a mean of 3-fold in patients with T2D and MASH treated with
lanifibranor (p=0.009) and lanifibranor in combination with empagliflozin (p=0.004) compared to no increase
measured in patients under placebo.

Regarding weight, the lanifibranor-only group saw a small increase of 3.6%, while the weight remained stable in
the group on lanifibranor and empagliflozin. Importantly, the ratio of visceral abdominal fat to subcutaneous fat
decreased in both groups of patients treated with lanifibranor alone or in combination with empagliflozin (-5 and
-18% respectively compared to +2% in the placebo group), reflecting a shift from pro-inflammatory visceral fat
towards metabolically healthy adipose tissue

Liver function tests (ALT, AST, GGT) and markers of liver fibrosis (TIMP-1, P3NP, Pro-C3) improved with
lanifibranor, whether used alone or in combination with empagliflozin. Other cardiometabolic health markers,
such as insulin sensitivity (HOMA-IR), inflammation (hs-CRP), ferritin, glycemia, and lipid levels (HDL-C,
triglycerides), also showed improvement in both treatment groups.

The details of the presentations are as follows:

Abstract title Combination therapy of lanifibranor with empagliflozin: metabolic improvement in
patients with Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Type-2
Diabetes (T2D)
Publication number 5040
Authors Michelle Lai, Onno Holleboom, Lucile Dzen, Philippe Huot-Marchand, Jean-Louis
Junien, Pierre Broqua, Louis Griffel, Sanjay Patel, Michael P Cooreman.
Date and time Monday, November 18th 8:00AM-5:00PM PST


Inventiva will exhibit from Saturday November 16, through Monday November 18th at booth #1445.



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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/NASH 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 3 clinical trial, NATiV3, for the
treatment of adult patients with MASH/NASH, a common and progressive chronic liver disease.

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 a 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


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@westwicke.com
+1 202 499 8937 Media relations +1 415 513-1284
inventiva@brunswickgroup.com
+33 1 53 96 83 83

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These statements include, but are not limited to, forecasts and estimates with respect to Inventiva’s pre-clinical
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results may turn out to be materially different from the anticipated future results, performance or achievements
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or development programs or be unable to expand its operations or otherwise capitalize on its business
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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
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and/or amendments to Inventiva’s clinical trials, Inventiva’s expectations with respect to the clinical development
plan for lanifibranor for the treatment of MASH/NASH may not be realized and may not support the approval of a
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cause adverse drug reactions or have other properties that could delay or prevent their regulatory approval, or
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and preclinical studies and clinical development programs and timelines, its financial condition and results of
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Inventiva’s and its partners’ clinical trials on anticipated timelines and the state of war between Israel and Hamas
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Please refer to the Universal Registration Document for the year ended December 31, 2023, filed with the Autorité
des Marchés Financiers on April 3, 2024, and the Annual Report on Form 20-F for the year ended December 31,
2023, filed with the Securities and Exchange Commission on April 3, 2024. Other risks and uncertainties of which
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the timing of events to differ materially from those anticipated. All information in this press release is as of the
date of the release. Except as required by law, Inventiva has no intention and is under no obligation to update or

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review the forward-looking 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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