MPS

Inventiva Announces Poster Presentation on a Promising Biomarker for MPS VI at the 15th International Symposium on MPS and Related Diseases

Inventiva Announces Poster Presentation on a Promising Biomarker for MPS VI at the 15th International Symposium on MPS and Related Diseases

July 26, 2018

Study to be presented demonstrates a robust quantitative method for measuring component GAG levels in leukocytes, enabling the identification of a reliable biomarker for MPS VI

Daix (France), July 26, 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 a poster presentation entitled “Intracellular GAG Level in Leukocytes is a Promising Pharmacodynamic Biomarker for MPS VI;” will be presented by Paul R. Harmatz, MD, UCSF Benioff Children’s Hospital Oakland, at the upcoming 15th International Symposium on MPS and Related Diseases being held on August 2-4, 2018 at the Sheraton San Diego Hotel & Marina, San Diego, California.

Dr. Harmatz noted: “Measuring intracellular glycosaminoglycan (GAG) levels in leukocytes may provide compelling surrogate markers, which could be used in clinical trials and for patient monitoring in MPS VI patients. MPS VI patients treated with enzyme replacement therapy (ERT) have high levels of chondroitin sulfate (CS) in leukocytes compared to age-matched healthy volunteers. Establishing a reliable biomarker in this patient population is important in the development of potential therapies such as odiparcil, an oral GAG clearance therapy from Inventiva, currently in clinical trials.”;

The details for the presentation are as follows:

Poster Title: “Intracellular GAG Level in Leukocytes is a Promising Pharmacodynamic Biomarker for MPS VI” (#024)
Speaker: Paul Harmatz, MD at the UCSF Benioff Children’s Hospital Oakland
Date: August 3, 2018
Time: 5:30 pm – 7:00 pm (PDT)
Location: Nautilus Room, Sheraton San Diego Hotel & Marina

About The Annual International Symposium on MPS and Related Diseases

The Annual International Symposium on MPS and Related Diseases, held this year in San Diego, California, provides an important opportunity for the MPS and related diseases community to share and exchange new information, to learn about new breakthroughs in science and medicine, and to develop relevant strategies. More information on the conference can be found at: www.mps2018.com

About odiparcil

Odiparcil is the first new treatment in development for MPS VI in over a decade. The current standard of care is enzyme replacement therapy (ERT), which requires weekly infusions. An orally available therapeutic such as odiparcil would greatly increase the quality of life of patients. More importantly, the data generated in MPS VI mice demonstrate that odiparcil could treat clinical manifestations linked to GAG accumulation in tissues and organs where current ERT is not effective. Odiparcil is well distributed in the body even in tissues that are poorly vascularized, such as cartilages, or protected by a barrier, such as the eye. Inventiva believes odiparcil could meaningfully improve the lives of MPS VI patients, and become the new standard of care. On December 30, 2017, the first patient was enrolled in the Phase IIa iMProveS (improve MPS treatment) trial of odiparcil in MPS VI patients. Results from this study are expected in H1 2019. Odiparcil has received orphan drug designation for MPS VI in the United States and Europe.

About MPS VI

MPS VI is a rare, pediatric, genetic, degenerative disease characterized by the abnormal functioning of the enzyme N-acetylgalactosamine 4-sulphatase (arylsulphatase B; ASB) leading to the accumulation of dermatan sulfate and chondroitin sulfate in the cells, tissues and organs. Patients suffer from short stature, corneal clouding, hearing loss, dysostosis multiplex, hepatosplenomegaly, cardiac valve disease and reduced pulmonary function. As with other MPS, the time of onset, rate of progression and extent of the disease may vary between the affected individuals. The life expectancy of MPS VI patients, if untreated, is approximately 20 years in patients with severe forms of the disease, or longer in patients with less severe forms. The prevalence of MPS VI is estimated to be 1 in 225,000 live births and varies between countries. There is no cure for MPS VI and current treatment options such as ERT or hematopoietic stem cell transplant (HSCT) leave the patients with high unmet medical needs.

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 outcomes of biomarker study measuring intracellular GAGs in leukocytes from MPS VI patients

Inventiva announces positive outcomes of biomarker study measuring intracellular GAGs in leukocytes from MPS VI patients

February 26, 2018

Data confirm highly promising biomarker for MPS VI and limited enzyme replacement therapy (ERT) efficacy in reducing leukoGAGs

Daix (France), February 26, 2018 – Inventiva, a biopharmaceutical company developing innovative therapies in nonalcoholic steatohepatitis (NASH), systemic sclerosis (SSc) and mucopolysaccharidosis (MPS), today announced the positive outcomes of a biomarker study to evaluate intracellular glycosaminoglycans (GAGs) levels in leukocytes as a disease activity biomarker in MPS VI. Conducted at UCSF Benioff Children’s Hospital in Oakland, California by Dr Paul R. Harmatz, and analyzed by the Greenwood Genetic Center Biochemical Genetics Laboratory in South Carolina, an international leader in the diagnosis of lysosomal storage disorders, this biomarker study has enabled the development of a new and robust quantification method of intracellular heparan sulfate (HS), chondroitin sulfate (CS) and dermatan sulfate (DS) in leukocytes (leukoGAG). These leukoGAGs may provide compelling surrogate markers to be used in clinical trials, and for patient monitoring. In addition, patients treated with galsulfase, the enzyme replacement therapy (ERT) approved for MPS VI patients, maintained a high level of leukoGAGs compared to age-matched healthy volunteers suggesting the possibility to further reduce this level with a new treatment such as odiparcil.

The study enrolled 12 subjects: six MPS VI patients, who have been treated with galsulfase for 10 ± 3.1 years (range 6-14 years), and six age-matched control subjects not affected with MPS. Urinary GAGs (uGAGs) and leukoGAGs were measured and the results show that all MPS VI patients receiving ERT have total uGAGs above the upper limit of normal (ULN) and leukoGAGs above control subjects values. In MPS VI patients receiving ERT, the most abundant GAG components are DS and CS in urine and CS in leucocytes. These two forms of GAGs are reduced in MPS VI patient cells treated with odiparcil. Finally, data on the arylsulfatase B activity (the deficient enzyme in MPS VI) in leukocytes, showed that one hour after completion of galsulfase infusion, enzyme activity is increased nearly eightfold but that the CS content in leucocytes remains more than 12-fold above basal level.

Dr. Paul R. Harmatz, the principal investigator of this study, said: “The high level of leukoGAG in patients receiving ERT is a clear signal of the limitations of this therapeutic strategy. Our ability to use a new and robust quantification method to measure intracellular HS/CS/DS will enrich our analysis of the Phase IIa iMProveS trial and are suggestive of the high medical need that can be addressed by odiparcil.”

About odiparcil

Odiparcil is the first new treatment in development for MPS VI in over a decade. The current standard of care is ERT, which requires weekly infusions. An orally available therapeutic such as odiparcil would greatly increase the quality of life of patients. More importantly, thanks to its optimal distribution in the body, odiparcil has shown efficacy in tissues and organs where current ERT is not effective. Inventiva believes odiparcil could meaningfully improve the lives of MPS VI patients, and become the new standard of care. On December 30th, 2017, the first patient was enrolled in the Phase IIa iMProveS (improve MPS treatment) trial of odiparcil in MPS VI patients. Results from this study are expected in 1H 2019. Odiparcil has received orphan drug designation for MPS VI in the United States and Europe in August 2017. Given its mechanism of action, odiparcil could address several forms of MPS where dermatan and/or chondroïtin sulfates GAGs accumulate: MPS I or Hurler/Scheie syndromes, MPS II or Hunter syndrome, MPS IVa or Morquio syndrome, MPS VI or Maroteaux-Lamy syndrome and MPS VII or Sly syndrome.

About MPS VI

MPS VI (Maroteaux-Lamy syndrome), is a rare, pediatric, genetic, degenerative disease characterized by the abnormal functioning of the enzyme N-acetylgalactosamine 4-sulphatase (arylsulphatase B; ASB) leading to the accumulation of chondroitin sulfate and dermatan sulfate in the cells, tissues and organs. Patients suffer from short stature, corneal clouding, hearing loss, dysostosis multiplex, hepatosplenomegaly, cardiac valve disease and reduced pulmonary function without intellectual deficit. As with other MPS, the time of onset, rate of progression and extent of the disease may vary between the affected individuals. The life expectancy of MPS VI patients, if untreated, is approximately 20 years in patients with severe forms of the disease, or longer in patients with less severe forms. The prevalence of MPS VI is estimated to be 1 in 225,000 live births and varies between countries. There is no cure for MPS VI and current treatment options such as ERT or hematopoietic stem cell transplant (HSCT) leave the patients with high unmet medical needs.

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 Enrollment of First Patient into Its Odiparcil Phase IIa Trial (iMProveS) for MPS VI

Inventiva Announces Enrollment of First Patient into Its Odiparcil Phase IIa Trial (iMProveS) for MPS VI

January 03, 2018

> Trial to enroll 24 patients at 2 clinical trial sites

> Results expected during the first semester of 2019

Daix (France), January 3, 2018 – Inventiva, a biopharmaceutical company developing innovative therapies, particularly to treat fibrosis, today announced the enrollment of the first patient in its Phase IIa iMProveS (improve MPS treatment) trial targeting mucopolysaccharidosis VI patients (MPS VI).

“Odiparcil is the first new treatment in development for MPS VI patients in over a decade and is a potentialsignificant step forward for patients,” said Jean-Louis Abitbol, M.D., M.Sc., Inventiva’s Chief Medical Officer and Head of Development, “Current enzyme replacement therapy requires weekly infusions, therefore an orally available therapeutic such as odiparcil would greatly increase the quality of life of patients. More importantly, thanks to its optimal distribution in the body, odiparcil has shown efficacy in tissues and organs where current enzyme replacement therapy is not effective. Overall we believe odiparcil could meaningfully improve the lives of these patients and become the standard of care in MPS VI.”

The iMProveS clinical study is a 26-week study designed to demonstrate the safety, tolerability, and efficacy of odiparcil in 18 adult MPS VI patients receiving enzyme replacement therapy (ERT). The study also has an open- label arm with 6 patients currently not on ERT. If positive, the Company plans to pursue a pivotal Phase III study of odiparcil in patients with MPS VI. Odiparcil has received orphan drug designation for MPS VI in the United States and Europe. Results from the Phase IIa study are expected during the first semester of 2019.

About MPS VI

MPS VI (Maroteaux-Lamy syndrome), is a rare, pediatric, genetic, degenerative disease characterized by the abnormal functioning of the enzyme N-acetylgalactosamine 4-sulphatase (arylsulphatase B; ASB) leading to the accumulation of dermatan sulfate and chondroitin sulfate in the cells, tissues and organs. Patients have coarse faces, short stature, corneal clouding, hearing loss, dysostosis multiplex, hepatosplenomegaly, cardiac valve disease and reduced pulmonary function without intellectual deficit. As with other MPS, the time of onset, rate of progression and extent of the disease may vary between the affected individuals. The life expectancy of MPS VI patients, if untreated, is approximately 20 years in patients with severe forms of the disease, or longer in patients with less severe forms. The prevalence of MPS VI is estimated to be 1 in 225,000 live births and varies between countries.

There is no cure for MPS VI and current treatment options such as enzyme replacement therapy (ERT) or hematopoietic stem cell transplant (HSCT) leave the patients with high unmet medical needs.

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 Odiparcil Awarded Orphan Drug Designation for the Treatment of MPS VI by the European Medicines Agency

Inventiva’s Odiparcil Awarded Orphan Drug Designation for the Treatment of MPS VI by the European Medicines Agency

August 29, 2017

> FDA Orphan Drug Designation received earlier this month

> EMA and FDA Orphan designations validate odiparcil potential to improve treatment options for MPS VI patients

> iMProveS phase IIa study in MPS VI patients on track to begin recruitment by year-end 2017

Daix (France), August 29, 2017 at 07:30am CEST – Inventiva, a biopharmaceutical company developing innovative therapies, particularly in fibrosis, today announced that the European Medicines Agency (EMA) has granted Orphan Drug Designation to odiparcil (formerly IVA336) for the treatment of MPS VI.

This decision could accelerate the availability of a much needed new treatment for MPS VI patients,;” said Christine Lavery, President of the UK MPS Society added Professor Chris Hendriksz, of FYMCA Medical Ltd. and University of Pretoria, South Africa.

We recently received U.S. orphan drug status and with this new EU designation we continue delivering on our regulatory strategy for odiparcil. Clearly the recent preclinical data we generated showing that odiparcil is active in organs where marketed enzyme replacement therapies have limited or no efficacy, has been instrumental in convincing regulators to grant these ODD designations. These designations confirm that regulatory agencies share our view that odiparcil could improve MPS VI current treatment options,” concluded Pierre Broqua, Chief Scientific Officer and Co-Founder of Inventiva.

MPS VI (Maroteaux-Lamy syndrome), is a rare pediatric genetic degenerative disease with a prevalence estimated to be 1 in 225,000 live births. There is no cure for MPS VI and current treatment options, such as enzyme replacement therapy (ERT) or hematopoietic stem cell transplant (HSCT), leave the patients with high unmet medical needs.

Odiparcil, an orally available therapy, is being developed as a potential therapy for MPS I, II, and VI patients. Inventiva is currently launching the Phase IIa iMProveS (improve MPS treatment) study, which is expected to enroll its first patient before year end. The iMProveS clinical study is a 26-week study designed to demonstrate the safety, tolerability, and efficacy of odiparcil in 24 adult MPS VI patients and will be conducted at two European clinical sites. If the results of this study are positive, the company plans to pursue a pivotal Phase III study of odiparcil in patients with MPS VI.

About Orphan Drug Designation

The EMA grants Orphan Drug Designation to support the development of medicines for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating and that affect no more than 5 in 10,000 individuals in the European Union. Orphan drug designation allows for companies to receive development incentives, such as protocol assistance, reduced fees for regulatory activities, and up to ten years of market exclusivity in the EU upon marketing approval for the designated indication.

About MPS VI

MPS VI (Maroteaux-Lamy syndrome), is a rare pediatric genetic degenerative diseases characterized by the abnormal functioning of the enzyme N-acetylgalactosamine 4-sulphatase (arylsulphatase B; ASB) leading to the accumulation of dermatan sulfate and chondroitin sulfate in the cells, tissues and organs. Patients have coarse faces, short stature, corneal clouding, hearing loss, dysostosis multiplex, hepatosplenomegaly, cardiac valve disease and reduced pulmonary function without intellectual deficit. As with other MPS, the time of onset, rate of progression and extent of the disease may vary between the affected individuals. The life expectancy of MPS VI patients, if untreated, is approximately 20 years in patients with severe forms of the disease, or longer in patients with less severe forms.

The prevalence of MPS VI is estimated to be 1 in 225,000 live births and varies between countries. There is no cure for MPS VI and current treatment options such as enzyme replacement therapy (ERT) or hematopoietic stem cell transplant (HSCT) leave the patients with high unmet medical needs.

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.

Odiparcil Awarded Orphan Drug Designation for the Treatment of MPS VI by the FDA

Odiparcil Awarded Orphan Drug Designation for the Treatment of MPS VI by the FDA

August 10, 2017

> Odiparcil therapeutic potential and significant benefit over existing therapeutic options confirmed

> With a high medical need still existing, odiparcil could significantly improve the treatment options for MPS VI patients

> First patient enrollment in a Phase IIa study expected by year-end 2017

Daix (France), August 10, 2017 at 5:45 pm CEST – Inventiva, a biopharmaceutical company developing innovative therapies, particularly in fibrosis, today announced that the FDA has granted Orphan Drug Designation to odiparcil (formerly IVA336) for the treatment of MPS VI.

MPS VI (Maroteaux-Lamy syndrome), is a rare pediatric genetic degenerative disease. The prevalence of MPS VI is estimated to be 1 in 225,000 live births. There is no cure for MPS VI and current treatment options such as enzyme replacement therapy (ERT) or hematopoietic stem cell transplant (HSCT) leave the patients with high unmet medical needs. “MPS are devastating diseases and odiparcil could become an important advance in providing optimal therapy for many patients struggling with lysosomal disorders,” said Professor Paul Harmatz (Children’s Hospital & Research Center of Oakland, Oakland, California).

“The FDA’s decision to award Orphan Drug Designation to odiparcil in the treatment of MPS VI patients is another important milestone as it confirms that odiparcil may bring a significant therapeutic benefit over existing approved medications”, added Pierre Broqua, Chief Scientific Officer and Co-Founder of Inventiva. “MPS VI remains a severe disease despite the availability of an enzyme replacement therapy, and this decision is a strong and encouraging signal from the FDA to move forward with our clinical program.”

Odiparcil, an orally available therapy, is being developed as a potential therapy for MPS I, II, and VI patients. Inventiva is currently launching the Phase IIa iMProveS (improve MPS treatment) study which is expected to enroll its first patient before year end. The iMProveS clinical study is a 26-week study designed to demonstrate the safety, tolerability, and efficacy of odiparcil in 24 adult MPS VI patients and will be conducted at two European clinical sites. If the results of this study are positive, the company plans to initiate a pivotal Phase III study in the US and in the EU with odiparcil in MPS VI patients.

About Orphan Drug Designation:

Orphan Drug Designation is granted by the FDA to novel therapeutics for diseases or conditions affecting fewer than 200,000 patients in the U.S. or greater than 200,000 patients if there is no reasonable expectation that the production cost of the drug will be covered by its sales. The designation allows the drug developer to be eligible for a seven-year period of

U.S. marketing exclusivity upon approval of the drug, as well as, in some cases, tax credits for clinical research costs, the ability to apply for annual grant funding, clinical trial design assistance, and the waiver of Prescription Drug User Fee Act (PDUFA) filing fees.

About MPS VI:

MPS VI (Maroteaux-Lamy syndrome), is a rare pediatric genetic degenerative diseases characterized by the abnormal functioning of the enzyme N-acetylgalactosamine 4-sulphatase (arylsulphatase B; ASB) leading to the accumulation of dermatan sulfate and chondroitin sulfate in the cells, tissues and organs. Patients have coarse faces, short stature, corneal clouding, hearing loss, dysostosis multiplex, hepatosplenomegaly, cardiac valve disease and reduced pulmonary function without intellectual deficit. As with other MPS, the time of onset, rate of progression and extent of the disease may vary between the affected individuals. The life expectancy of MPS VI patients, if untreated, is approximately 20 years for patients with severe forms of the disease and more for patients with less severe forms.

The prevalence of MPS VI is estimated to be 1 in 225,000 live births. It varies between countries. There is no cure for MPS VI and current treatment options such as enzyme replacement therapy (ERT) or hematopoietic stem cell transplant (HSCT) leave the patients with high unmet medical needs.

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 New Compelling Data on Odiparcil/IVA336 to be Presented at MPS Society National Conference

Inventiva Announces New Compelling Data on Odiparcil/IVA336 to be Presented at MPS Society National Conference

June 29, 2017

> Confirmation of potential to be the first orally available substrate reduction therapy for MPS VI patients

> Phase IIa iMProveS clinical study scheduled to begin before year end 2017

Daix (France), June 29, 2017 – 6:00pm CEST – Inventiva, a biopharmaceutical company developing innovative therapies, particularly to treat fibrosis, today announced that Professor Chris Hendriksz, of FYMCA Medical Ltd. and University of Pretoria, South Africa, will be presenting new preclinical data on Odiparcil (formerly IVA336) in a closed session at the MPS Society National Conference, which will be held July 7-9, 2017 in Coventry, UK.

The data, generated over a 6-month treatment with two doses of Odiparcil in a genetic mouse model for MPS VI, demonstrate that Odiparcil restored a normal corneal structure in the eye, which could lead to a complete rescue of the disease phenotype in the eye. Odiparcil also reduced GAG accumulation in the liver, kidney, spleen, heart, eye, and skin of diseased animals and produced a dose-dependent reduction of cartilage thickness in the trachea and femoral growth plate. Finally mobility was improved by Odiparcil in the diseased animals.

These results demonstrate that Odiparcil has the potential to be the first orally available substrate reduction therapy for MPS VI patients. “These breakthrough pre-clinical results support the potential of Odiparcil as a new and very promising approach to treating MPS patients,” said Professor Hendriksz. “MPS are devastating diseases, and there remains a significant unmet medical need despite the availability of enzyme replacement therapies, which unfortunately are not able to resolve the symptoms occurring in certain regions especially in the ophthalmological system, joints, cartilages, cardiac valves etc. Odiparcil could prove beneficial to MPS patients as a substrate reduction therapy as a stand-alone treatment or in adjunction to current treatments.”

We are very excited by the data, as well as the positive feedback received from patients’ associations and MPS key opinion leaders. We are looking forward to the upcoming iMProveS trial, which could confirm the therapeutic benefit of Odiparcil, leading potentially to ERT replacement,” added Pierre Broqua, Ph.D., Chief Scientific Officer and Co-Founder of Inventiva.

In addition to the Odiparcil data, Professor Hendriksz will also present the design of the planned Phase IIa iMProveS (improve MPS treatment) clinical study, which is expected to enroll its first patient before year end. The iMProveS clinical study will be a 26-week study designed to demonstrate the safety, tolerability, and efficacy of Odiparcil in 24 adult MPS VI patients and will be conducted at two European clinical sites. Eighteen patients receiving enzyme replacement treatment (ERT) will be randomized into 3 arms: two active dose levels of Odiparcil (250 mg and 500 mg, bid) or placebo. The study will also include an additional arm of six patients untreated by ERT who will receive 500 mg bid of Odiparcil. This study, if positive, will allow for enrollment of MPS VI patients into the pivotal Phase III trial.

For more information on the MPS Society National Conference, refer to http://www.mpssociety.org.uk/2017/01/11/programme-uk-mps-conference-announced/

About MPS VI:

MPS VI (Maroteaux-Lamy syndrome), is a rare pediatric genetic degenerative diseases characterized by the abnormal functioning of the enzyme N-acetylgalactosamine 4-sulphatase (arylsulphatase B; ASB) leading to the accumulation of dermatan sulfate and chondroitin sulfate in the cells, tissues and organs. Patients have coarse faces, short stature, corneal clouding, hearing loss, dysostosis multiplex, hepatosplenomegaly, cardiac valve disease and reduced pulmonary function without intellectual deficit. As with other MPS, the time of onset, rate of progression and extent of the disease may vary between the affected individuals. The life expectancy of MPS VI patients, if untreated, is approximately 20 years for patients with severe forms of the disease and more for patients with less severe forms.

The prevalence of MPS VI is estimated to be 1 in 225,000 live births. It varies between countries. There is no cure for MPS VI and current treatment options such as enzyme replacement therapy (ERT) or hematopoietic stem cell transplant (HSCT) leave the patients with high unmet medical needs.

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.