Lanifibranor

Inventiva Announces Two Poster Presentations at the American College of Rheumatology Conference

Inventiva Announces Two Poster Presentations at the American College of Rheumatology Conference

October 10, 2018

Posters to focus on the anti-fibrotic effect of lanifibranor and the alteration of the PPAR pathway in a mouse model of systemic sclerosis (SSc)

Daix (France), October 10, 2018 – Inventiva S.A. (“Inventiva” or the “Company”), a biopharmaceutical company developing innovative therapies in nonalcoholic steatohepatitis (NASH), systemic sclerosis (SSc) and mucopolysaccharidosis (MPS), today announced that two abstracts on the anti-fibrotic effect of lanifibranor and the alteration of the PPARpathway in a mouse model of systemic scleorderma will be presented at the upcoming American College of Rheumatology (ACR) conference being held on October 19-24, 2018 in Chicago, Ilinois. These two posters were prepared as part of the development of lanifibranor as a treatment for SSc, for which the results of the Phase IIb study FASST (For a Systemic Sclerosis Treatment) are expected in early 2019.

The first abstract, entitled “In vivo assessment of lung fibrosis’ prevention using the pan-PPAR agonist lanifibranor in the TβRIIΔk-fib (Transgenic Mouse Model of Scleroderma) mouse model of systemic sclerosis”, shows the impact of Inventiva’s lanifibranor in the treatment of lung fibrosis in a mouse model of SSc. In this model, where transgenic (TG) mice display severe and persistent fibrosis compared to wildtype (WT), lanifibranor produced a significant protection from lung fibrosis compared to controls, reinforcing the rationale for lanifibranor trials in SSc, especially for patients showing lung fibrosis.

The second abstract, entitled “Evidence for Altered Peroxisome Proliferator Activated Receptor (PPAR) Pathway Activity in a Transgenic Mouse Model of Scleroderma (TβRIIΔk-fib): Analysis of Mouse Skin, Lung and Explanted Cells;”, examines the evidence of PPAR pathway perturbations in whole tissue or explanted cells from adult or neonatal TβRIIΔk-fib;TG mice compared to WT littermates. Results suggests that the PPARpathway is downregulated in TG mice.

Pierre Broqua, Chief Scientific Officer and Co-Founder of Inventiva, commented “The data to be presented at the ACR reinforces our confidence in the potential of our lead product lanifibranor, with which we aim to address important unmet medical needs in the treatment of NASH and SSc;. We are currently evaluating lanifibranor in two parallel Phase IIb clinical studies in NASH and SSc and look forward to presenting top-line results from the SSc trial in early 2019;.”

The event details for the presentations are as follows:

Poster Titles: “In vivo assessment of lung fibrosis’ prevention using the pan-PPAR agonist lanifibranor in the TβRIIΔk-fib mouse model of systemic sclerosis”;“Evidence for Altered Peroxisome Proliferator Activated Receptor (PPAR) Pathway Activity in a Transgenic Mouse Model of Scleroderma (TβRIIΔk-fib): Analysis of Mouse Skin, Lung and Explanted Cells;”
Session Title: Systemic Sclerosis and Related Disorders – Basic Science Poster I & Poster II
Date: Sunday, October 21st and Monday, October 22nd
Time: 9:00AM- 11:00AM (CST)
Location: ACR poster sessions A and B

About lanifibranor

Lanifibranor is a next generation panPPAR modulator, designed as a moderately potent and well-balanced PPAR α, γ and δ. This unique profile was conceived in order to obtain an optimal therapeutic margin with strong efficacy and tolerance. Lanifibranor is currently being evaluated in two parallel Phase IIb clinical studies in NASH and SSc as well as in a Phase II trial in diabetic patients with NAFLD (non-alcoholic fatty liver disease).

Contacts

Inventiva
Frédéric Cren

Chief Executive Officer
info@inventivapharma.com
+33 3 80 44 75 00

Brunswick
Julien Trosdorf / Yannick Tetzlaff

Media relations
inventiva@brunswickgroup.com
+33 1 53 96 83 83

LifeSci Advisors
Monique Kosse

Investor relations
monique@lifesciadvisors.com

About Inventiva
Inventiva is a biopharmaceutical company specialized in the development of drugs interacting with nuclear receptors, transcription factors and epigenetic modulators. Inventiva’s research engine opens up novel breakthrough therapies against fibrotic diseases, cancers and orphan diseases with substantial unmet medical needs.

Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.

Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.

Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.

Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.

Important Notice
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development
plans, business and regulatory strategy, and anticipated future performance of Inventiva and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management”s beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva”s control.

There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.

Please refer to the “Document de référence” filed with the Autorité des Marchés Financiers on April 13, 2018 under n° R.18-013 for additional information in relation to such factors, risks and uncertainties.

Inventiva has no intention and is under no obligation to update or 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.

Inventiva advances in the development of lanifibranor with the achievement of three key milestones

Inventiva advances in the development of lanifibranor with the achievement of three key milestones

August 30, 2018

> New patent granted by the USPTO protecting the use of lanifibranor in numerous fibrotic diseases

> Enrolment of first patient in the United States Phase II study for the treatment of NAFLD in patients with type 2 diabetes

> FDA approval of the IND application enabling to launch the clinical development plan in the United States

Daix (France), August 30, 2018 – Inventiva S.A. (“Inventiva” or the “Company”), a biopharmaceutical company developing innovative therapies in nonalcoholic steatohepatitis (NASH), systemic sclerosis (SSc) and mucopolysaccharidosis (MPS), today announced the successful completion of three key milestones in the development of its lead product, lanifibranor.

New patent granted by the USPTO protecting the use of lanifibranor in numerous fibrotic diseases

On August 21, 2018, the United States Patent and Trademark Office (USPTO) granted a new patent protecting until June 2035 the therapeutic use of lanifibranor in the treatment of various fibrotic conditions, including NASH and SSc.

This patent strengthens and extends in the United States the term of protection of lanifibranor derived from the New Chemical Entity (NCE) patent expiring in December 2031 (this expiration date includes a possible five-year extension to compensate for regulatory delays in obtaining the marketing approval).

Enrolment of the first patient in the United States Phase II study for the treatment of NAFLD in patients with type 2 diabetes

Following the agreement with the University of Florida to conduct a Phase II study in the United States with lanifibranor for the treatment of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes, the first of 64 patients for this study has been enrolled in August 2018. The recruitment of the other patients continues in accordance with the planned schedule and top line results are expected in early 2020.

The overall objective of the study , led by Dr Kenneth Cusi, Head of the Department of Endocrinology, Diabetes & Metabolism in the Department of Medicine at the University of Florida at Gainesville, is to measure the metabolic improvements induced by lanifibranor, as well as its effects on hepatic steatosis in patients with type 2 diabetes and NAFLD. In addition, this study will examine the impact of lanifibranor on fibrosis using the latest imaging and biomarker technologies.

FDA approval of the IND application enabling to launch the clinical development plan in the United States

On August 24, 2018, the Company received the approval of its IND (Investigational New Drug) application from the gastroenterology division of the FDA (Food and Drug Administration) for lanifibranor in order to conduct a drug interaction study required to pursue the development program.

This approval is an important milestone as it will allow Inventiva to use this IND to initiate further clinical studies for lanifibranor’s development in NASH in the United States.

Frédéric Cren, CEO and co-founder of Inventiva, said: “These three important achievements demonstrate the continued progress made in the clinical development of lanifibranor and confirm our confidence in the future of our lead product. The new patent granted by the USPTO is a tangible proof of the innovative nature of our therapeutic approach with lanifibranor and above all extends the date of exclusivity by several years.”;

About lanifibranor

Lanifibranor is a next generation panPPAR modulator, designed as a moderately potent and well balanced PPAR ?, ? and ?. This unique profile was conceived in order to obtain an optimal therapeutic margin with strong efficacy and tolerance. Inventiva is currently evaluating lanifibranor in two parallel Phase IIb clinical studies in NASH and SSc.

Contacts

Inventiva
Frédéric Cren

Chief Executive Officer
info@inventivapharma.com
+33 3 80 44 75 00

Brunswick
Julien Trosdorf / Yannick Tetzlaff

Media relations
inventiva@brunswickgroup.com
+33 1 53 96 83 83

LifeSci Advisors
Monique Kosse

Investor relations
monique@lifesciadvisors.com

About Inventiva
Inventiva is a biopharmaceutical company specialized in the development of drugs interacting with nuclear receptors, transcription factors and epigenetic modulators. Inventiva’s research engine opens up novel breakthrough therapies against fibrotic diseases, cancers and orphan diseases with substantial unmet medical needs.

Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.

Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.

Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.

Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.

Important Notice
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development
plans, business and regulatory strategy, and anticipated future performance of Inventiva and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management”s beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva”s control.

There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.

Please refer to the “Document de référence” filed with the Autorité des Marchés Financiers on April 13, 2018 under n° R.18-013 for additional information in relation to such factors, risks and uncertainties.

Inventiva has no intention and is under no obligation to update or 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.

Inventiva’s lanifibranor found to have good safety profile following first assessment of carcinogenicity studies’ results

Inventiva’s lanifibranor found to have good safety profile following first assessment of carcinogenicity studies’ results

August 13, 2018

> Two-year studies now completed confirming long-term safety of lanifibranor

> Both studies should be deemed adequate according to preliminary assessment

> Results to be presented to FDA

> Results to allow initiation of Phase III clinical trials

Daix (France), August 13, 2018 – Inventiva, a biopharmaceutical company developing innovative therapies in nonalcoholic steatohepatitis (NASH), systemic sclerosis (SSc), and mucopolysaccharidosis (MPS), today reported the successful completion of two two-year carcinogenicity studies with the pan-PPAR agonist lanifibranor.

A preliminary assessment was performed by Dr. Jeri El-Hage, toxicologist and regulatory consultant and expert in the PPAR field at Aclairo Pharmaceutical Development Group, indicating that both studies should be deemed adequate based on correct dosing and good tolerability.

In my assessment of the results from the studies, it is clear that the toxicological profile of lanifibranor is relatively benign;” said Dr. El-Hage. “The studies were well conducted with excellent survival rates and tolerability and results show an improved safety profile compared to other dual- and pan-PPARs. Lanifibranor displays a good cardiac safety profile and in my opinion the results of these studies should allow lanifibranor to enter into Phase III”.

The two carcinogenicity studies in rats and in mice were initiated in October 2015 after study protocol approval by the US Food and Drug Administration (FDA). They were conducted by Envigo (United Kingdom), a Contract Research Organization (CRO) with expertise in running similar studies, particularly with compounds from the PPAR class. The studies assessed the effects of three doses of lanifibranor, administered daily for a 104-week period, compared to control groups.

The results of these studies will be presented to the FDA’s Executive Carcinogenicity Assessment Committee (ECAC) in order to obtain the authorization to enter into Phase III. The special protocol assessments for the studies had been reviewed by the ECAC and the doses evaluated were approved for both studies.

“With the completion of these carcinogenicity studies, Inventiva has now finalized the regulatory toxicological package necessary to enter into Phase III with lanifibranor,” declared Pierre Broqua, Chief Scientific Officer and co-founder of Inventiva. “The data demonstrate a good safety profile and we look forward to receiving feedback from the FDA in the coming months.”

About lanifibranor

Lanifibranor is a next generation panPPAR modulator designed as a moderately potent and well balanced PPAR α, γ and δ. This unique profile was conceived in order to obtain an optimal therapeutic margin with strong efficacy and tolerance. Inventiva is currently evaluating lanifibranor in two parallel Phase IIb clinical studies in NASH and SSc.

Contacts

Inventiva
Frédéric Cren

Chief Executive Officer
info@inventivapharma.com
+33 3 80 44 75 00

Brunswick
Julien Trosdorf / Yannick Tetzlaff

Media relations
inventiva@brunswickgroup.com
+33 1 53 96 83 83

LifeSci Advisors
Monique Kosse

Investor relations
monique@lifesciadvisors.com

About Inventiva
Inventiva is a biopharmaceutical company specialized in the development of drugs interacting with nuclear receptors, transcription factors and epigenetic modulators. Inventiva’s research engine opens up novel breakthrough therapies against fibrotic diseases, cancers and orphan diseases with substantial unmet medical needs.

Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.

Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.

Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.

Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.

Important Notice
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development
plans, business and regulatory strategy, and anticipated future performance of Inventiva and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management”s beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva”s control.

There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.

Please refer to the “Document de référence” filed with the Autorité des Marchés Financiers on April 13, 2018 under n° R.18-013 for additional information in relation to such factors, risks and uncertainties.

Inventiva has no intention and is under no obligation to update or 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.

Inventiva Announces Positive DSMB Reviews in both NASH and Systemic Sclerosis Phase IIb Trials with Lanifibranor

Inventiva Announces Positive DSMB Reviews in both NASH and Systemic Sclerosis Phase IIb Trials with Lanifibranor

July 10, 2018

> Both DSMB recommend trials to continue without changing the protocol

> Lanifibranor safety is confirmed

> Trials to continue as planned

Daix (France) June 20, 2018 – Inventiva S.A. (“Inventiva” or the “Company”), a biopharmaceutical company developing innovative therapies in nonalcoholic steatohepatitis (“NASH”), systemic sclerosis (“SSc”) and mucopolysaccharidosis (“MPS”), today announced that the FASST (For A Systemic Sclerosis Treatment) Data Safety Monitoring Board (“DSMB”) held its third and last meeting before the end of the trial of lanifibranor in SSc. Similarly to the conclusions of the first two DSMBs , the board recommended that the study continue without any modification to the protocol. Similarly the NATIVE (NASH Trial to Validate IVA337 Efficacy) DSMB met for the first time and after reviewing all safety data came to a similar conclusion and recommended to continue the study without any modification of the protocol. The positive outcomes of these two DSMBs confirm the good safety of lanifibranor, already demonstrated in long-term toxicological studies as well as in phase I and phase II clinical trials. Both studies are progressing as planned with no specific concerns and topline results are anticipated in early 2019 for the FASST trial in SSc and second half of 2019 for the NATIVE trial in NASH.

About Lanifibranor:

Lanifibranor is a next generation panPPAR modulator designed as a moderately potent and well balanced PPAR α, γ and δ. This unique profile was conceived in order to obtain an optimal therapeutic margin with strong efficacy and tolerance. Inventiva is currently evaluating lanifibranor in two parallel Phase IIb clinical studies in NASH and SSc.

About the Phase IIb FASST trial:

The Phase IIb FASST trial is a one-year randomized double-blind study designed to measure the effect of lanifibranor on the progression of systemic sclerosis (SSc). Patients will receive either lanifibranor or placebo according to the study protocol, approved by the European Medicines Agency (EMA). The primary endpoint is change in the Modified Rodnan Skin Score (MRSS), which is a measure of disease progression accepted by both Food and Drug Administration (FDA) and the EMA. Inclusion criteria are based on a MRSS between 10 and 25, and diffuse systemic sclerosis diagnosed from less than 3 years. Patients are allowed to continue their ongoing treatments, including immunosuppressive therapies. Lanifibranor has been granted orphan drug status for the treatment of systemic sclerosis by the EMA and the FDA. The orphan drug status provides certain advantages for the sponsor such as reduced procedure costs and commercial exclusivity.

About the Phase IIb NATIVE trial:

The Phase IIb NATIVE trial is a 24-week randomized double-blind study designed to assess the efficacy of lanifibranor on ballooning and inflammation without worsening of fibrosis. Patients will receive either lanifibranor or placebo. This trial will also evaluate the safety of lanifibranor treatment. The main inclusion and assessment criteria of the study are based on the hepatic histology of each patient: (i) NASH histological diagnosis according to the NASH Clinical Research Network criteria (steatosis, lobular inflammation of any degree and liver cell ballooning of any amount) and (ii) SAF activity score of 3 or 4 (> 2), SAF Steatosis score >= 1 and SAF Fibrosis score < 4. The primary endpoint of the study is a decrease in relation to the baseline of >= 2 points of the SAF activity score combining hepatocellular inflammatory and ballooning.

Contacts

Inventiva
Frédéric Cren

Chief Executive Officer
info@inventivapharma.com
+33 3 80 44 75 00

Brunswick
Julien Trosdorf / Yannick Tetzlaff

Media relations
inventiva@brunswickgroup.com
+33 1 53 96 83 83

LifeSci Advisors
Monique Kosse

Investor relations
monique@lifesciadvisors.com

About Inventiva
Inventiva is a biopharmaceutical company specialized in the development of drugs interacting with nuclear receptors, transcription factors and epigenetic modulators. Inventiva’s research engine opens up novel breakthrough therapies against fibrotic diseases, cancers and orphan diseases with substantial unmet medical needs.

Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.

Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.

Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.

Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.

Important Notice
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development
plans, business and regulatory strategy, and anticipated future performance of Inventiva and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management”s beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva”s control.

There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.

Please refer to the “Document de référence” filed with the Autorité des Marchés Financiers on April 13, 2018 under n° R.18-013 for additional information in relation to such factors, risks and uncertainties.

Inventiva has no intention and is under no obligation to update or 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.

Inventiva Announces a U.S. Phase II Investigator-Initiated Study with Lanifibranor on Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes

Inventiva Announces a U.S. Phase II Investigator-Initiated Study with Lanifibranor on Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes

April 03, 2018

Dr. Kenneth Cusi of the University of Florida to be principal investigator
Trial in 64 patients to begin after the FDA has approved lanifibranor IND

Daix (France), April 3rd, 2018 – Inventiva, a biopharmaceutical company developing innovative therapies in nonalcoholic steatohepatitis (NASH), systemic sclerosis (SSc) and mucopolysaccharidosis (MPS), today announced that Dr. Kenneth Cusi, Chief of the Division of Endocrinology, Diabetes & Metabolism in the Department of Medicine at the University of Florida, Gainesville, has selected lanifibranor for a Phase II investigator-initiated clinical trial. The trial’s objective is to evaluate the efficacy and safety of lanifibranor on intrahepatic triglycerides and hepatic insulin sensitivity in type 2 diabetic patients with nonalcoholic fatty liver disease (NAFLD). A positive result would further reinforce lanifibranor as the ideal drug for NAFLD and NASH patients with type 2 diabetes (T2DM).

Lanifibranor is a new generation panPPAR agonist that activates the alpha, gamma and delta isoforms of the peroxisome proliferator-activated receptors (PPARs). Lanifibranor selection for this study was motivated by this unique mechanism of action that can potentially address all key features of NAFLD and NASH: improvement of insulin-sensitivity, steatosis reduction, anti-inflammatory activity and reduction of fibrosis. In parallel to this investigator-initiated study, Inventiva is currently conducting two lanifibranor Phase IIb clinical trials in NASH and SSc. The Company has been granted orphan drug designation for lanifibranor by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in SSc.

“PPARs are clinically validated targets to treat patients suffering from NAFLD or NASH. Lanifibranor with its moderate and balanced panPPAR profile and its gamma activity, is a very promising candidate adressing most if not all the components of NASH” Dr. Cusi said. “We anticipate this profile will translate well into type 2 diabetic patients affected by NAFLD or NASH and are confident in the success of this trial.”

Jean-Louis Abitbol, MD, MSC, Chief Medical Officer of Inventiva, said: “We are delighted that Dr. Cusi, a renowned expert in the PPAR field and world-class clinician has selected lanifibranor for this study that will provide us with additional supportive data for our regulatory filings of lanifibranor with U.S. and European regulators.”;

Pierre Broqua, Chief Scientific Officer and a co-founder of Inventiva, added: “We are extremely excited by this collaboration with Dr Cusi. This study meets several of our strategic objectives with a contained financial investment, including opening an IND1, initiating a study in the US in a population likely to benefit from lanifibranor treatment and enlarge the clinical data package for future interactions with FDA.”;

The trial conducted by Dr. Cusi is expected to enroll 64 patients treated for a 24-week period with a single daily dose of lanifibranor (800mg/day) and 10 subjects in a healthy, non-obese control group. The study’s overall objective is to measure the metabolic effects of lanifibranor, and its potential efficacy on steatosis in T2DM patients with NAFLD. Additionally this study will detect lanifibranor impact on fibrosis using the most recent imaging technology. The main endpoints are a decrease of liver steatosis assessed by state of the art imaging, including H-MRS (Proton Magnetic Resonance Spectroscopy), evidence of metabolic improvements in insulin resistance (glucose clamp, HBA1c), de novo lipogenesis, free fatty acids, lipids and safety. The trial should begin in Q2/Q3 2018 depending on FDA approval of lanifibranor IND filing.

Webcast

A webcast on this study will be held in English on April 5th, 2018 at 6:15pm CEST. To join, please use the code 5361123 after dialing one of the following numbers:

France: +33 (0)1 76 77 22 57
Belgium: +32 (0)2 400 6926
Denmark: +45 35 15 81 21
Germany: +49 (0)69 2222 2018
Netherlands: +31 (0)20 703 8261
Switzerland: +41 (0)22 567 5750
United Kingdom: +44 (0)330 336 9411
United States: +1 323-794-2093

The presentation accompanying this webcast will be available on Inventiva’s website at 6:15pm CEST on the same day in the “Investor” – “Documentation” – “Investor presentations” section and can be followed live at the same time at: https://edge.media-server.com/m6/p/rg74y7wv

A replay of the webcast and presentation will be available from 9:30pm CEST onwards on the same day at: https://edge.media-server.com/m6/p/rg74y7wv

IND: Investigational New Drug

Contacts

Inventiva
Frédéric Cren

Chief Executive Officer
info@inventivapharma.com
+33 3 80 44 75 00

Brunswick
Julien Trosdorf / Yannick Tetzlaff

Media relations
inventiva@brunswickgroup.com
+33 1 53 96 83 83

LifeSci Advisors
Monique Kosse

Investor relations
monique@lifesciadvisors.com

About Inventiva
Inventiva is a biopharmaceutical company specialized in the development of drugs interacting with nuclear receptors, transcription factors and epigenetic modulators. Inventiva’s research engine opens up novel breakthrough therapies against fibrotic diseases, cancers and orphan diseases with substantial unmet medical needs.

Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.

Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.

Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.

Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.

Important Notice
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development
plans, business and regulatory strategy, and anticipated future performance of Inventiva and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management”s beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva”s control.

There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.

Please refer to the “Document de référence” filed with the Autorité des Marchés Financiers on April 13, 2018 under n° R.18-013 for additional information in relation to such factors, risks and uncertainties.

Inventiva has no intention and is under no obligation to update or 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.

Lanifibranor carcinogenicity studies: Progressing as planned and interim results in rats indicate no compound related urinary bladder tumors

Lanifibranor carcinogenicity studies: Progressing as planned and interim results in rats indicate no compound related urinary bladder tumors

March 28, 2018

Daix (France), March 28, 2018 – Inventiva, a biopharmaceutical company developing innovative therapies in nonalcoholic steatohepatitis (NASH), systemic sclerosis (SSc), and mucopolysaccharidosis (MPS), today reported preliminary results of the two-year carcinogenicity studies with the pan-PPAR agonist lanifibranor in rats. Two carcinogenicity studies in rats and in mice were started in October 2015 after study protocol approval by the US Food and Drug Administration (FDA) and executed by Envigo (UK), a Contract Research Organization (CRO) with previous expertise in running similar studies, particularly with compounds from the PPAR class. These studies tested the effects of three doses of lanifibranor administered daily for a 104-week period, compared to control groups. This first in-life phase was conducted as planned and histopathology evaluation of the two studies is nearly completed. The peer-review phase of the two studies in rats and mice is expected to be finalized by the end of the second quarter 2018.

The peer-review is ongoing and preliminary results of the study in rats are already available, indicating that there are no compound-related incidences of neoplastic lesions, and in particular no increased incidence of urinary bladder cancer, a finding that was reported for several single or dual PPAR compounds. Lanifibranor’s moderate and balanced panPPAR profile and different chemical structure could explain the benign profile of the compound.

Doctor J. Armstrong, senior pathologist in charge of the peer-review, commented: “The peer-review is ongoing and preliminary results of the study in rats from the incident tables indicate a very benign safety profile of lanifibranor. I am particularly pleased that no primary urinary bladder neoplasms were diagnosed in the treated rats, a finding that was reported for several other PPAR compounds.”

Pierre Broqua, Chief Scientific Officer and a co-founder of Inventiva, added: “These preliminary results in rats are in line with the good safety profile of the moderately potent and well-balanced pan-PPAR agonist lanifibranor, demonstrated in long-term toxicological studies as well as in clinical Phase I and Phase II studies. Since bladder tumors have been associated with several different PPAR compounds, the carcinogenicity studies of lanifibranor are a critical part of the overall development package. While the study is not yet completed for both species, we are encouraged by the clean lanifibranor profile in the rat study, where there were no signs of increased bladder tumor incidence in any of the lanifibranor dose groups. We look forward to reviewing the full results from both species within the coming months.”

These two carcinogenicity studies are being carried out as part of the lanifibranor development plan and are a regulatory requirement for lanifibranor commercialization.

About lanifibranor:

Lanifibranor is a next generation pan-PPAR modulator designed as a moderately potent and well-balanced PPAR   and . This unique profile was conceived in order to obtain an optimal therapeutic margin with strong efficacy and tolerance. Lanifibranor displayed an antifibrotic efficacy superior to selective PPAR-α, PPAR-δ or PPAR- agonists in several relevant preclinical models. Inventiva is conducting two Phase IIb clinical studies in NASH and SSc with lanifibranor.

Contacts

Inventiva
Frédéric Cren

Chief Executive Officer
info@inventivapharma.com
+33 3 80 44 75 00

Brunswick
Julien Trosdorf / Yannick Tetzlaff

Media relations
inventiva@brunswickgroup.com
+33 1 53 96 83 83

LifeSci Advisors
Monique Kosse

Investor relations
monique@lifesciadvisors.com

About Inventiva
Inventiva is a biopharmaceutical company specialized in the development of drugs interacting with nuclear receptors, transcription factors and epigenetic modulators. Inventiva’s research engine opens up novel breakthrough therapies against fibrotic diseases, cancers and orphan diseases with substantial unmet medical needs.

Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.

Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.

Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.

Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.

Important Notice
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development
plans, business and regulatory strategy, and anticipated future performance of Inventiva and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management”s beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva”s control.

There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.

Please refer to the “Document de référence” filed with the Autorité des Marchés Financiers on April 13, 2018 under n° R.18-013 for additional information in relation to such factors, risks and uncertainties.

Inventiva has no intention and is under no obligation to update or 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.

Inventiva’s paper on the discovery and synthesis of its panPPAR agonist lanifibranor accepted and published in the Journal of Medicinal Chemistry of the American Chemical Society

Inventiva’s paper on the discovery and synthesis of its panPPAR agonist lanifibranor accepted and published in the Journal of Medicinal Chemistry of the American Chemical Society

March 13, 2018

Lanifibranor is in Phase IIb development for non-alcoholic steatohepatitis (NASH) and systemic sclerosis (SSc)

Daix (France) March 13, 2018 – Inventiva, a biopharmaceutical company developing innovative therapies in nonalcoholic steatohepatitis (NASH), systemic sclerosis (SSc) and mucopolysaccharidosis (MPS), today announced the publication of an article online, ahead of print, describing the discovery of its promising panPPAR agonist, lanifibranor, in the Journal of Medicinal Chemistry of the American Chemical Society. The Journal of Medicinal Chemistry is one of the most important journals in medicinal chemistry.

Pierre Broqua, Chief Scientific Officer and Inventiva’s co-founder, said: “We’re delighted to have our paper published by the prestigious Journal of Medicinal Chemistry. Of particular interest is the data showing how lanifibranor has a specific binding into the PPAR pocket, a further explanation to the excellent safety profile demonstrated so far by lanifibranor, our lead clinical candidate currently in Phase IIb trials in NASH and SSc.”

Background

Peroxisome proliferator-activated receptors (PPARs) play a key role in controlling the fibrotic process. Inventiva’s lead program lanifibranor is an anti-fibrotic treatment with a powerful mechanism of action that activates all three alpha, gamma and delta PPARs. Currently two lanifibranor Phase IIb trials are ongoing in NASH and SSc. Inventiva has been granted orphan drug designation for lanifibranor in the treatment of SSc by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Journal of Medicinal Chemistry publication

The study now published in the Journal of Medicinal Chemistry sets out in detail how Inventiva’s research team discovered lanifibranor, and what they believe are the benefits of this novel compound.

Starting from a high-throughput screening hit, an extensive medicinal chemistry optimization campaign led to the discovery of lanifibranor. Xray co-crystal structure of lanifibranor bound to PPARdisplayed a new atypical binding mode in comparison to rosiglitazone. The compound’s head to tail positioning stabilizes a conformationally active form of PPARwithout interacting directly with Helix H12. The authors believe that lanifibranor’s non-classical binding mode, its different coregulator recruitment profile and its balanced activity for the three PPAR isoforms may well explain its good safety profile relative to other PPAR agonists.

Furthermore, lanifibranor demonstrated excellent anti-hyperglycemic and hypolipidemic efficacy in a relevant mouse model, and a significant anti-fibrotic activity in a mouse model for liver fibrosis. Compared to other PPAR agonists, lanifibranor had no effect on hematocrit, plasma volume or heart weight in rats. These encouraging results provide ample rationale for the further development of lanifibranor in NASH.

Link to publication & reference:

Design, synthesis and evaluation of a novel series of indole sulfonamide Peroxisome Proliferator Activated Receptors (PPAR)α/δ/γ triple activators: discovery of lanifibranor a new anti-fibrotic clinical candidate https://pubs.acs.org/doi/10.1021/acs.jmedchem.7b01285
J. Med. Chem., DOI: 10.1021/acs.jmedchem.7b01285

Contacts

Inventiva
Frédéric Cren

Chief Executive Officer
info@inventivapharma.com
+33 3 80 44 75 00

Brunswick
Julien Trosdorf / Yannick Tetzlaff

Media relations
inventiva@brunswickgroup.com
+33 1 53 96 83 83

LifeSci Advisors
Monique Kosse

Investor relations
monique@lifesciadvisors.com

About Inventiva
Inventiva is a biopharmaceutical company specialized in the development of drugs interacting with nuclear receptors, transcription factors and epigenetic modulators. Inventiva’s research engine opens up novel breakthrough therapies against fibrotic diseases, cancers and orphan diseases with substantial unmet medical needs.

Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.

Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.

Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.

Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.

Important Notice
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development
plans, business and regulatory strategy, and anticipated future performance of Inventiva and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management”s beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva”s control.

There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.

Please refer to the “Document de référence” filed with the Autorité des Marchés Financiers on April 13, 2018 under n° R.18-013 for additional information in relation to such factors, risks and uncertainties.

Inventiva has no intention and is under no obligation to update or 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.

Inventiva Announces Positive DSMB Review in Phase IIb FASST Trial in Systemic Sclerosis with Lanifibranor

Inventiva Announces Positive DSMB Review in Phase IIb FASST Trial in Systemic Sclerosis with Lanifibranor

January 04, 2018

> DSMB recommends trial to continue unchanged

> 145 patients randomized in trial

> Topline results anticipated early 2019

Daix (France) January 4, 2018 – Inventiva, a biopharmaceutical company developing innovative breakthrough therapies, particularly for the treatment of fibrotic diseases, today announced that the Data Safety Monitoring Board (DSMB) has completed its review of the Phase IIb FAAST (For A Systemic Sclerosis Treatment) trial in systemic sclerosis with lanifibranor. After reviewing all safety data, including adverse events, and the study’s conduct, the DSMB recommended that the study continue without any modifications to the protocol. Of the 145 randomized patients enrolled into the trial, 100 patients have been treated for 6 months including 54 patients that have already completed the one year treatment. The study is progressing as planned with no specific concerns and topline results are anticipated in early 2019.

About Lanifibranor:

Lanifibranor is a next generation panPPAR modulator designed as a moderately potent and well balanced PPAR α δ and y. This unique profile was conceived in order to obtain an optimal therapeutic margin with strong efficacy and tolerance. Lanifibranor displayed an antifibrotic efficacy superior to selective PPARα, PPAR δ or PPARy agonists in several relevant preclinical models. Inventiva is also conducting a Phase IIb clinical study in NASH with lanifibranor.

About the Phase IIb FASST trial:

The Phase IIb FASST trial is a one-year randomized double-blind study designed to measure the effect of lanifibranor on the progression of systemic sclerosis (SSc). Patients will receive either lanifibranor or placebo according to the study protocol, approved by the European Medicines Agency (EMA). The primary endpoint is change in the Modified Rodnan Skin Score (MRSS), which is a measure of disease progression accepted by both Food and Drug Administration (FDA) and the EMA. Inclusion criteria are based on a MRSS between 10 and 25, and diffuse systemic sclerosis diagnosed from less than 3 years. Patients are allowed to continue their ongoing treatments, including immunosuppressive therapies. Lanifibranor has been granted orphan drug status for the treatment of systemic sclerosis by the EMA and the FDA. The orphan drug status provides certain advantages for the sponsor such as reduced procedure costs and commercial exclusivity.

About systemic sclerosis:

Systemic sclerosis is a rare and complex disease affecting the auto-immune system, the microvascular system and conjunctive tissues. This fibrotic disease mainly affects the skin, but also the lungs, the heart, the gastro-intestinal tract, and the kidneys. Due to the progressive failure of different organs, systemic sclerosis is a severe disease with a high mortality rate. Once patients are diagnosed with systemic sclerosis, generally between the ages of 40 and 50, the median survival period is of 11 years. Close to 170,000 people suffer from systemic sclerosis worldwide, with women outnumbering men by a ratio of more than five to one1.

The disease owes its original name to scleroderma, the skin condition that it provokes, which derives from the Greek words skleros (hard) and derma (skin). The disease causes severe physical and psycho-social consequences; the former may be fatal for patients whose vital organs are affected. Deeper study of this skin fibrosis has led to its classification into two sub-categories, respectively called limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis. The latter is more serious and is targeted in the FASST trial.

To date, only symptomatic drugs with limited therapeutic effects are available in order to attenuate the consequences of fibrosis progression. However, they do not prevent, delay or reverse the disease’s devastating process.

Contacts

Inventiva
Frédéric Cren

Chief Executive Officer
info@inventivapharma.com
+33 3 80 44 75 00

Brunswick
Julien Trosdorf / Yannick Tetzlaff

Media relations
inventiva@brunswickgroup.com
+33 1 53 96 83 83

LifeSci Advisors
Monique Kosse

Investor relations
monique@lifesciadvisors.com

About Inventiva
Inventiva is a biopharmaceutical company specialized in the development of drugs interacting with nuclear receptors, transcription factors and epigenetic modulators. Inventiva’s research engine opens up novel breakthrough therapies against fibrotic diseases, cancers and orphan diseases with substantial unmet medical needs.

Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.

Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.

Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.

Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.

Important Notice
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development
plans, business and regulatory strategy, and anticipated future performance of Inventiva and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management”s beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva”s control.

There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.

Please refer to the “Document de référence” filed with the Autorité des Marchés Financiers on April 13, 2018 under n° R.18-013 for additional information in relation to such factors, risks and uncertainties.

Inventiva has no intention and is under no obligation to update or 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.

Inventiva’s Phase IIb FASST Trial in Systemic Sclerosis with Lanifibranor Completes Enrollment

Inventiva’s Phase IIb FASST Trial in Systemic Sclerosis with Lanifibranor Completes Enrollment

October 17, 2017

> Enrollment complete – 145 patients randomized

> A total of 47 clinical sites in 10 countries actively recruited patients

> Headline results expected in early 2019

Daix (France) October 17, 2017 – 06:00 pm CEST – Inventiva, a biopharmaceutical company developing innovative breakthrough therapies, particularly for the treatment of fibrotic diseases, today announced that it has completed the enrollment of its Phase IIb FASST (For A Systemic Sclerosis Treatment) trial in Systemic Sclerosis (SSc) with lanifibranor, formerly known as IVA337. FASST is progressing well and investigators have enrolled and randomized 145 patients. Headline results are expected in early 2019.

“We are pleased to have achieved this important enrollment milestone in the development of lanifibranor for the treatment of systemic sclerosis,” said Dr. Jean-Louis Abitbol, Chief Medical Officer and Head of Development of Inventiva. “The decision to open new countries and sites has resulted in a larger number of patients recruited and a slightly longer than anticipated recruitment period. We are very grateful to the patients and our network of investigators for the achievement of this important milestone.”

The FASST trial protocol meets EMA and FDA approval standards. Therefore, if the results of the FASST Phase IIb are positive, we are very confident that lanifibranor will be successful in the pivotal Phase III,;” added Professor Yannick Allanore, Professor of Rheumatology at Ho?pital Cochin ;in Paris and co-Principal Investigator of the FASST trial with Professor Chris Denton, Professor of Experimental Rheumatology at University College London.

Systemic sclerosis is a serious disease with a high unmet medical need. Current treatments mainly manage complications or provide symptomatic relief whereas lanifibranor has the potential to modify the course of the disease, thus representing a significant step forward for patients. We are looking forward to the result of this trial and to lanifibranor further development,;” said Dominique Godard, President of the French SSc Association.

Lanifibranor is a next generation panPPAR modulator designed as a moderately potent and well balanced PPAR α δ and y agonist. This unique profile was designed in order to obtain an optimal therapeutic margin with strong anti-fibrotic efficacy and tolerance. Preclinical data also demonstrate that lanifibranor has the potential to treat pulmonary arterial hypertension a condition often associated with SSc. Inventiva is also progressing a Phase IIb clinical study in NASH (non-alcoholic steatohepatitis) with lanifibranor.

About the Phase IIb FASST trial:

The Phase IIb FASST trial is a one-year randomized double-blind study designed to measure the effect of lanifibranor on the progression of SSc. Patients will receive either lanifibranor or placebo according to the study protocol, approved by the European Medicines Agency (EMA). The primary endpoint is change in the Modified Rodnan Skin Score (MRSS), which is a measure of disease progression accepted by both the FDA and the EMA. Inclusion criteria are based on a MRSS between 10 and 25, and diffuse systemic sclerosis diagnosed from less than 3 years. Patients are permitted to continue with their ongoing treatments, including immunosuppressive therapies. Lanifibranor has been granted orphan drug status for the treatment of systemic sclerosis by the EMA and the FDA. The orphan drug status provides certain advantages for the sponsor such as reduced procedure costs and commercial exclusivity.

About systemic sclerosis:

Systemic sclerosis is a rare and complex disease affecting the auto-immune system, the microvascular system and conjunctive tissues. This fibrotic disease mainly affects the skin, but also the lungs, the heart, the gastro-intestinal tract, and the kidneys. Due to the progressive failure of different organs, systemic sclerosis is a severe disease with a high mortality rate. Once patients are diagnosed with systemic sclerosis, generally between the ages of 40 and 50, the median survival period is of 11 years. Close to 170,000 people suffer from systemic sclerosis, with women outnumbering men by a ratio of more than five to one 1.

.The disease owes its original name of scleroderma, which derives from the Greek words skleros (hard) and derma (skin), to the skin condition it provokes. The disease causes severe physical and psycho-social consequences; the former may be fatal for patients whose vital organs are affected. Deeper study of this skin fibrosis has led to its classification into two sub- categories, respectively called limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis. The latter is more serious and is targeted in the FASST trial.

To date, only symptomatic drugs with limited therapeutic effects are available in order to attenuate the consequences of fibrosis progression. However, they do not prevent, delay or reverse the disease’s devastating process.

1 Journal of Rheumatology, 2013

Contacts

Inventiva
Frédéric Cren

Chief Executive Officer
info@inventivapharma.com
+33 3 80 44 75 00

Brunswick
Julien Trosdorf / Yannick Tetzlaff

Media relations
inventiva@brunswickgroup.com
+33 1 53 96 83 83

LifeSci Advisors
Monique Kosse

Investor relations
monique@lifesciadvisors.com

About Inventiva
Inventiva is a biopharmaceutical company specialized in the development of drugs interacting with nuclear receptors, transcription factors and epigenetic modulators. Inventiva’s research engine opens up novel breakthrough therapies against fibrotic diseases, cancers and orphan diseases with substantial unmet medical needs.

Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.

Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.

Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.

Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.

Important Notice
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development
plans, business and regulatory strategy, and anticipated future performance of Inventiva and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management”s beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva”s control.

There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.

Please refer to the “Document de référence” filed with the Autorité des Marchés Financiers on April 13, 2018 under n° R.18-013 for additional information in relation to such factors, risks and uncertainties.

Inventiva has no intention and is under no obligation to update or 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.

Inventiva’s IVA337 Given Generic Name “Lanifibranor” by the World Health Organization (WHO)

Inventiva’s IVA337 Given Generic Name “Lanifibranor” by the World Health Organization (WHO)

September 18, 2017

> Lanifibranor (formerly IVA337) is the first next generation panPPAR α δ and y to receive the fibranor suffix

> Lanifibranor is the Inventiva’s lead drug candidate currently in Phase IIb development for both systemic sclerosis (SSc) and non-alcoholic steatohepatitis (NASH)

Daix (France), September 18, 2017 at 05:45pm CEST – Inventiva, a biopharmaceutical company developing innovative breakthrough therapies, particularly for the treatment of fibrotic diseases, today announced that the World Health Organization (WHO) has granted it the international non-proprietary name (INN, or generic name) lanifibranor for IVA337, its leading drug candidate, currently is in Phase IIb development for both systemic sclerosis (SSc) and non-alcoholic steatohepatitis (NASH).

“We are very pleased that the INN division of the WHO has granted the suffix “fibranor“ to IVA337,” said Frédéric Cren, Chief Executive Officer and Co-Founder of Inventiva. “Lanifibranor’s anti-fibrotic activity ideally positions this drug candidate as a potential treatment of several fibrotic diseases, particularly systemic sclerosis and NASH. We look forward to continuing the clinical development of this drug candidate in these two indications with high unmet medical need.”

About Lanifibranor

Lanifibranor is a next generation panPPAR modulator designed as a moderately potent and well balanced PPAR α δ and y. This unique profile was conceived in order to obtain an optimal therapeutic margin with strong efficacy and tolerance. Lanifibranor is currently in Phase IIb development for both systemic sclerosis (SSc) and non-alcoholic steatohepatitis (NASH). Results from the SSc clinical trial are expected in the second half of 2018, while those of the NASH trial are due for early 2019.

Contacts

Inventiva
Frédéric Cren

Chief Executive Officer
info@inventivapharma.com
+33 3 80 44 75 00

Brunswick
Julien Trosdorf / Yannick Tetzlaff

Media relations
inventiva@brunswickgroup.com
+33 1 53 96 83 83

LifeSci Advisors
Monique Kosse

Investor relations
monique@lifesciadvisors.com

About Inventiva
Inventiva is a biopharmaceutical company specialized in the development of drugs interacting with nuclear receptors, transcription factors and epigenetic modulators. Inventiva’s research engine opens up novel breakthrough therapies against fibrotic diseases, cancers and orphan diseases with substantial unmet medical needs.

Lanifibranor, its lead product, is an anti-fibrotic treatment acting on the three alpha, gamma and delta PPARs (peroxisome proliferator-activated receptors), which play key roles in controlling the fibrotic process. Its anti-fibrotic action targets two initial indications with substantial unmet medical need: NASH, a severe and increasingly prevalent liver disease already affecting over 30 million people in the United States, and systemic sclerosis, a disease with a very high mortality rate and for which there is no approved treatment to date.

Inventiva is also developing a second clinical program with odiparcil (IVA 336) for the treatment of patients with mucopolysaccaridosis type VI (or Maroteaux-Lamy syndrome), a rare and severe gene disease affecting children. Odiparcil has also the potential to address other MPS types, characterized by the accumulation of chondroitin or dermatan sulfate (MPS I or Hurler/Sheie syndrome, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome and MPS VII or Sly syndrome). Inventiva is also developing a portfolio of early research projects in the field of oncology.

Inventiva benefits from partnerships with world-leading research entities such as the Institut Curie in the field of oncology. Two strategic partnerships have also been established with world-class major pharmaceutical companies AbbVie and Boehringer Ingelheim in the fields of autoimmune diseases (specifically in psoriasis) and fibrosis respectively. These partnerships provide milestone payments to Inventiva upon the achievement of pre-clinical, clinical, regulatory and commercial milestones, in addition to royalties on the products resulting from the partnerships.

Inventiva employs over 100 employees and owns R&D facilities near Dijon, acquired from the international pharmaceutical group Abbott. The Company owns, a proprietary chemical library of over 240,000 molecules as well as integrated biology, chemistry, ADME and pharmacology platforms.

Important Notice
This press release contains forward-looking statements, forecasts and estimates with respect to the clinical development
plans, business and regulatory strategy, and anticipated future performance of Inventiva and of the market in which it operates. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management”s beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva”s control.

There can be no guarantees with respect to pipeline product candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. Therefore, actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements.

Please refer to the “Document de référence” filed with the Autorité des Marchés Financiers on April 13, 2018 under n° R.18-013 for additional information in relation to such factors, risks and uncertainties.

Inventiva has no intention and is under no obligation to update or 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.

1