Clinical Studies

Inventiva Announces Poster Presentation on Its YAP/TEAD Inhibitor Program at the EORTC-NCI-AACR Symposium in Dublin

Inventiva Announces Poster Presentation on Its YAP/TEAD Inhibitor Program at the EORTC-NCI-AACR Symposium in
Dublin

Novembre 7, 2018

Recent results reveal potential of oral small molecules in pre-clinical development by Inventiva targeting the YAP/TEAD pathway as a potential therapy in the treatment of mesothelioma and non-small cell lung cancer

Daix (France), November 7, 2018 – Inventiva S.A. (“Inventiva” or the “Company”), a biopharmaceutical company developing innovative therapies in non-alcoholic steatohepatitis (NASH), systemic sclerosis (SSc), and mucopolysaccharidosis (MPS), today announced that it will be presenting a poster on its YAP/TEAD pre-clinical program at the upcoming EORTC-NCI-AACR Molecular Targets and Therapeutics Symposium being held on November 13-16, 2018 in Dublin, Ireland.

The poster to be presented, entitled “Discovery of promising anti-cancer drug combination using YAP-TEAD inhibitors with standard of care treatment in mesothelioma and NSCLC cells”, illustrates some of the recent data observed by Inventiva in pre-clinical studies, which suggest that the YAP/TEAD inhibitor molecules being investigated by the Company may have potential as a therapy in the treatment of mesothelioma, Non-Small Cell Lung Cancer (NSCLC) and other cancers.

Inventiva’s YAP/TEAD approach aims at disrupting the formation of the transcriptional complex formed by YAP and TEAD, which are believed to be key players in the oncogenic process as well as in fibrogenesis.

Inventiva has observed that its lead YAP/TEAD inhibitor molecules have prevented the formation of the YAP/TEAD transcriptional complex in vitro and are associated with a reduction of YAP/TEAD target genes expression and anti-proliferative effects in cancer cell lines where proliferation is under the control of the Hippo pathway. The Company has also observed in xenograft and patient-derived xenograft (PDX) mice models that its YAP/TEAD inhibitor molecules exhibited activity both as a stand-alone treatment or in combination with standard of care.

Based on these promising results, the Company plans to finalize the toxicological studies necessary to advance its YAP/TEAD program into Phase I/II clinical development in 2019.

“We have made significant progress in our understanding of the Hippo pathway, which offers exciting potential for the treatment of rare and prevalent cancers,” stated Pierre Broqua, Chief Scientific Officer and cofounder of Inventiva. “We have observed that our patented small molecules exhibited activity both as a stand-alone treatment and in combination with standard of care in pre-clinical models. In addition, molecules that inhibit the YAP/TEAD interaction have already shown a potential to overcome drug resistance and tumor escape mechanisms, which makes this pathway particularly interesting. Our program is advancing well and we are looking forward to see it progressing into Investigational New Drug (IND) enabling studies.”

The event details for the presentations are as follows:

Poster Title: “Discovery of promising anti-cancer drug combination using YAP-TEAD inhibitors with standard of care treatment in mesothelioma and NSCLC cells”
Session Title: Drug Resistance and Modifiers
Date: Tuesday, November 13th
Time: 10am to 2pm
Location: The Convention Centre, Spencer Dock, North Wall Quay, Dublin, Ireland

About the EORTC-NCI-AACR Symposium

Hosted by the European Organization for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR), the 30th edition of the EORTC-NCI-AACR Symposium in 2018 brings together academics, scientists and industry representatives to discuss the latest developments in drug development, target selection and the impact of new discoveries in molecular biology.

 

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 Last Visit by Last Patient in its Phase IIb SSc Trial and Second Positive DSMB Review in its Phase IIb NASH Trial with Lanifibranor

Inventiva Announces Last Visit by Last Patient in its Phase IIb SSc Trial and Second Positive DSMB Review in its Phase IIb NASH Trial with Lanifibranor

October 15, 2018

> Top-line results of the Phase IIb systemic sclerosis (SSc) trial are expected for early 2019

> Second NASH DSMB recommends to continue the trial with lanifibranor without changing the protocol

Daix (France), October 15, 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 last visit by the last patient in its Phase IIb FASST (For A Systemic Sclerosis Treatment) trial as well as the second positive review of the Data Safety Monitoring Board (DSMB) in its Phase IIb NATIVE (NASH Trial to Validate IVA337 Efficacy) trial, both conducted with lanifibranor.

The last visit of the last patient of the 12-month FAAST study took place on October 12 and data-base lock is planned for early January 2019. With this positive background, the Company confirmed that it expects to announce top-line results of the study in early 2019 as previously announced.

“SSc is a debilitating disease with no disease-modifying treatments approved so far where lanifibranor mechanism of action could prove beneficial for our patients. Given that all three DSMB meetings regarding the FASST trial recommended to pursue with the study without any modifications to the protocol, we are very eager to see the results of this study,” said Yannick Allanore, co-principal investigator of the FASST trial and professor of rheumatology at the Hôpital Cochin in Paris.

Professor Christopher Denton, co-principal investigator of the FASST trial and professor at the University College London, added: “The FASST trial is a long-term study in SSc patients that will evaluate clinical endpoints highly relevant to clinicians, patients and health authorities. Positive results in this study would therefore be very supportive to the development of lanifibranor as a treatment in this very severe disease.”

Additionally, the DSMB from the Company’s NATIVE trial in NASH patients held its second meeting. Out of the 101 patients randomized so far, the DSMB had access to the data of 95 patients of which 36 had completed the 6 month treatment period of the study. Based on its analysis, the DSMB recommended the study to continue without any modification of the protocol.

Pierre Broqua, CSO and cofounder of Inventiva, stated: “We are very satisfied with the progress of the FASST study and excited by the prospect of publishing the head-line results early next year. The results of the second DSMB meeting regarding our NATIVE study are also very encouraging and headline results are expected for the first half of 2020.”

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 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 Food and Drug 1

Administration (FDA) and EMA. Inclusion criteria are based on a MRSS between 10 and 25 points, and diffuse SSc 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 SSc by the EMA and the FDA (respectively in November 2014 and March 2015). 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 receive either lanifibranor or placebo. This trial also evaluates 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 inflammation and ballooning.

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 launches an independent working group to help increase NASH awareness and establish best practices for its treatment

Inventiva launches an independent working group to help increase NASH awareness and establish best practices for its treatment

September 24, 2018

Daix (France), September 24th, 2018 – Inventiva S.A. (“Inventiva” or the “Company”), a biopharmaceutical company developing innovative therapies in nonalcoholic steatohepatitis (NASH), systemic sclerosis (SSc) and mucopolysaccharidosis (MPS), announced today the creation of the panNASH?* initiative, a working group consisting of a committee of international independent experts that aims to increase the visibility and contribute to a better understanding of NASH, to share their expertise and to establish best practices for the treatment of the disease.

The initiative, which is supported by Inventiva, includes European and American medical experts in areas related to NASH such as hepatology, diabetes and cardiology, along with renowned scientific experts focused on promoting a better understanding of the physiopathological mechanisms involved in NASH (see the list of the founding members at the end of this press release);. Their aim will therefore be to play an active role in developing and disseminating their NASH expertise among the scientific community, patients and other key stakeholders within the healthcare system.

In particular, the experts group intends to help develop and share new findings about NASH through publications, conferences and training sessions. It will particularly focus on the development of the disease, the identification of patients at risk, clinical markers and associated health risks, as well as the development of new treatments. Specifically, the committee will help to increase knowledge of pathological mechanisms ranging from metabolic disorders to fibrosis and comorbidities, with a focus on the modulating role played by PPARs (peroxisome proliferator-activated receptors, subtypes).

Frédéric Cren, Chairman, Chief Executive Officer and co-founder of Inventiva, stated: “This working group brings together recognized NASH experts with unique and complementary skills and represents a further commitment by Inventiva to become a key player in the development of a treatment for this disease. I am confident that the program will lead to a better understanding of NASH by the various stakeholders. The group’s work will play a key role in establishing best practices for the treatment of NASH, a serious disease for which there is not yet any approved treatment, but which is one of society’s most widespread metabolic diseases, with 30 million patients already affected in the USA alone.”

The first meeting of the panNASH(TM) initiative took place in Geneva on September 22, 2018 following the NAFLD Summit 2018 ;organized by European Association for the Study of the Liver (EASL).

Committee members

Specialist field

Country

Name

Affiliation

Hepatology

Belgium

Pr. Sven Francque

Antwerp University Hospital

Hepatology

Germany

Pr. Frank Tacke

University Hospital Aachen

Hepatology

Switzerland

Pr. Jean-François Dufour

University Clinic Bern

Hepatology

US

Pr. Manal Abdelmalek

Duke University

Hepatology

US

Pr. Gyongyi Szabo

University of Massachusetts

Diabetology

Germany

Pr. Michael Roden

Heinrich Heine University

Diabetology

US

Pr. Kenneth Cusi

University of Florida

Cardiology

UK

Pr. Christopher Byrne

University of Southampton

Cardiology

US

Pr. Frank Sacks

Harvard T.H. Chan School of Public Health

*panNASH is an initiative coordinated by Terra Firma

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 to Present the Latest Findings in its RORγ program at the 256th National Meeting of the American Chemical Society

Inventiva to Present the Latest Findings in its RORγ program at the 256th National Meeting of the American Chemical Society

August 01, 2018

Daix (France), August 1st, 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 Dominique Potin, Inventiva’s Principal Scientist of Medicinal Chemistry, will give a presentation on the Company’s ROR? program, entitled “Discovery of novel quinoline sulfonamide derivatives as potent, selective and orally active ROR;? inverse agonists;”, at the 256th National Meeting of the American Chemical Society being held on August 19-23, 2018 at the Boston Convention & Exhibition Center (BCEC) in Boston, Massachusetts.

Dr. Potin will present results from a high throughput screening of Inventiva’s library of 248,000 compounds using a GAL4 transactivation assay, which has led to the discovery of a new series of quinoline sulfonamides as potent orally inverse ROR? inhibitors. Dr. Potin will discuss the synthesis, structure activity relationship (SAR) and biological activity of these derivatives.

Inventiva and AbbVie, a global, research and development-based biopharmaceutical company, have entered into an agreement to discover and develop available ROR? inverse agonists which has led to the development of several orally available inverse ROR? inhibitors, showing activity in vivo both in a target engagement model and disease models. The most advanced compound, ABBV-157, has demonstrated a good safety profile during GLP- tox studies and has been selected to enter into Phase I clinical studies. Under the terms of the agreement, Inventiva is eligible for development and sales milestones as well as royalties on sales.

Dr. Potin commented: “Targeting the IL-17 pathway has become a very attractive approach for the treatment of immuno-inflammatory diseases in recent years. IL-17 antibodies such as secukinumab have validated the interest of blocking IL-17 secretion for such therapy. The nuclear receptor ROR?t is a critical element in the regulation of IL-17. It does indeed play a key role in the differentiation and development of Th17 cells that secrete IL-17A and other pro-inflammatory cytokines, like IL-17F and IL-22. Small molecule ROR?t inhibitors could be useful for the treatment of various diseases such as psoriasis or inflammatory bowel disease.”;

The details of the presentation are as follows:

Presentation Title: “Discovery of novel quinoline sulfonamide derivatives as potent, selective and orally active RORy inverse agonists”
Speaker: Dr. Dominique Potin, Principal Scientist of Medicinal Chemistry, Inventiva
Session Title:General Oral Session
Date:August 19, 2018
Time: 09:30 am (Eastern Time)
Location: MEDI 10, room 210A, Boston Convention & Exhibition Center (BCEC)

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.

FDA Approval of an Investigator Initiated IND Application to Conduct Phase II Study of Lanifibranor in Type 2 Diabetic Patients with Non-Alcoholic Fatty Liver Disease

FDA Approval of an Investigator Initiated IND Application to Conduct Phase II Study of Lanifibranor in Type 2 Diabetic Patients with Non-Alcoholic Fatty Liver Disease

June 20, 2018

> Study to enroll first patient in the third quarter 2018 with topline results expected early 2020

> FDA approval is a positive signal for SSc and NASH IND applications

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 U.S. Food and Drug Administration (FDA) has accepted the investigator initiated Investigational New Drug (IND) application providing clearance to proceed with the Phase II study of lanifibranor in type 2 diabetic patients with nonalcoholic fatty liver disease (NAFLD). This FDA approval is also a positive signal for the planned Company IND applications in SSc and NASH.

The trial to be conducted by Dr. Kenneth Cusi, Chief of the Division of Endocrinology, Diabetes & Metabolism in the Department of Medicine at the University of Florida, Gainesville, is expected to enroll 64 patients treated for a 24-week period with a single daily dose of lanifibranor (800 mg/day) or placebo and 10 subjects in a healthy, non-obese control group. The study’s overall objective is to measure the metabolic improvements induced by lanifibranor, and its effect on steatosis in type 2 diabetic patients with NAFLD. Additionally, this study will detect lanifibranor’s impact on fibrosis using the most recent imaging and biomarker technology. Its main endpoints are a decrease of liver steatosis assessed by state-of-the-art imaging, including H-MRS (Proton Magnetic Resonance Spectroscopy), a decrease of insulin resistance (glucose clamp, HBA1c), a decrease in de novo lipogenesis, and safety. The first patient is expected to be enrolled in the third quarter of 2018 and topline results are expected beginning of 2020.

“With its unique pan-PPAR profile, lanifibranor has shown very good safety features, relevant efficacy data in NASH preclinical models as well as positive metabolic effects in a Phase IIa study in diabetic patients,” Dr. Cusi said. “We anticipate the results of this study to translate well to diabetic patients with NAFLD or NASH and look forward to demonstrating that lanifibranor could become a very valuable drug for these patients.”

Jean-Louis Abitbol, MD, MSC, Chief Medical Officer of Inventiva, added: “We are delighted that the FDA has allowed Dr Cusi and his team to proceed with this exciting metabolic and imaging study and we very much look forward to the enrollement of US patients as these results will provide additional supporting data for our regulatory filings with US and European regulators.”

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.