Boehringer Ingelheim and Inventiva collaborate to develop potential new treatments for idiopathic pulmonary fibrosis

May 31, 2016

> New collaboration to harness the therapeutic potential of a promising novel target for the treatment of Idiopathic Pulmonary Fibrosis (IPF)

> Total deal value up to €170 million, plus tiered sales royalties

Ingelheim, Germany and Daix, France, 31 May, 2016 – Boehringer Ingelheim and Inventiva, a French biopharmaceutical company specialized in the development of innovative therapies for fibrosis, oncology and orphan diseases, announced today, a new multi-year research and drug discovery collaboration and licensing agreement.

Under the terms of the agreement, the Inventiva and Boehringer Ingelheim research teams will jointly validate a new therapeutic concept with the aim of discovering new medicines for the treatment of Idiopathic Pulmonary Fibrosis (IPF) and other fibrotic diseases. The partnership will combine Inventiva’s deep knowhow and proprietary technologies in the field of transcriptional regulation and fibrosis with Boehringer Ingelheim’s capabilities in drug discovery and clinical development of new therapeutic agents.

The new collaboration is an example of Boehringer Ingelheim’s increasing focus on external innovation and builds on the company’s track record in IPF drug development. Boehringer Ingelheim has successfully developed nintedanib (OFEV®), a small molecule tyrosine kinase inhibitor, approved and marketed globally for the treatment of IPF in adults and will be responsible for clinical development and commercialization of potential drug candidates from the collaboration.

IPF is a debilitating and fatal lung disease with high mortality, affecting as many as 3 million people worldwide. It is characterized by chronic scaring and remodeling of the lung and progressive decline in lung function. IPF is the most common interstitial lung disease encountered worldwide and poses a major public health threat, as 70% to 80% of patients die within only 5 years from the diagnosis. To date, the cause of IPF is unidentified and despite recent progress treatment options for patients are still limited.

“We are very proud to enter into this collaboration with Boehringer Ingelheim, a company well- reputed for its excellent research and development skills in the field of fibrosis, and particularly Idiopathic Pulmonary Fibrosis,” commented Inventiva’s co-founder and CSO Pierre Broqua. We plan, alongside developing our own pipeline, on pursuing our strategy of establishing collaborative research partnerships with the world’s biggest pharmaceutical companies. This new partnership further testifies to Inventiva’s expertise and contributes to strengthening our position as a leading and innovative actor in the field of fibrosis.”

“We are enthusiastic about this partnership and look forward to collaborating with Inventiva’s team to develop a potential new breakthrough therapy for the treatment of Idiopathic Pulmonary Fibrosis,” concluded Clive R. Wood, Ph.D., Senior Corporate Vice President Discovery Research at Boehringer Ingelheim. “We are impressed by Inventiva’s research and drug discovery competencies and deep knowledge of the field. We firmly believe that joining forces with Inventiva will enable us to foster translation of an aspirational new therapeutic concept into eagerly awaited new therapies for patients.”

Inventiva will receive an upfront payment and is eligible to receive research funding, potential research, development, regulatory and commercial milestone payments of up to €170 million and tiered royalties on net sales of the products resulting from the partnership. Full financial details remain undisclosed.

About idiopathic pulmonary fibrosis

IPF is a debilitating and fatal lung disease with high mortality,14 affecting as many as 3 million people worldwide. 15,16 Progression of IPF is variable and unpredictable, and over time the lung function of an IPF patient gradually and irreversibly declines.14 

IPF causes permanent scarring or fibrosis of the lung, difficulty breathing and decreases the amount of oxygen the lungs can supply to major organs of the body.17 This is because over time, as the tissue thickens and stiffens with scarring, the lungs lose their ability to take in and transfer oxygen into the bloodstream.17 As a result, individuals with IPF experience shortness of breath, a non- productive cough and often have difficulty participating in everyday physical activities.18

About OFEV® (nintedanib)

OFEV®, a small molecule tyrosine kinase inhibitor developed by Boehringer Ingelheim researchers, is indicated in adults for the treatment of IPF.In 2015 OFEV® was included in the updated international treatment guidelines for IPF.2

OFEV® slows disease progression with approximately 50% reduction in the decline of lung function across a broad range of IPF patient types.1,3-9 This includes patients with early disease (minimal lung function impairment FVC >90% predicted),limited radiographic scarring (no honeycombing) on high resolution computed tomography (HRCT)and those with emphysema. Side effects with OFEV® can be effectively managed in most patients with diarrhea being the most frequently reported side effect.3

OFEV® targets growth factor receptors, which have been shown to be involved in the mechanisms by which pulmonary fibrosis occurs.1,10 Most importantly OFEV® inhibits platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR).10-12 It is believed that OFEV® reduces disease progression in IPF and slows the decline in lung function by blocking the signaling pathways that are involved in fibrotic processes.11-13

About Boehringer Ingelheim

Boehringer Ingelheim is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally through 145 affiliates and a total of some 47,500 employees. The focus of the family-owned company, founded in 1885, is on researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects through, for example, the initiative “Making MoreHealth” while also caring for employees. Respect, equal opportunity and reconciling career and family form the foundation of mutual cooperation. The company also focuses on environmental protection and sustainability in everything it does.

In 2015, Boehringer Ingelheim achieved net sales of about 14.8 billion euros. R&D expenditure corresponds to 20.3 per cent of net sales.

For more information please visit www.boehringer-ingelheim.com

  1. OFEV® Summary of Product Characteristics. Boehringer Ingelheim International GmbH. January 2016.
  2. Raghu G, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guidelines: Treatment of Idiopathic Pulmonary Fibrosis: Executive Summary. American Journal of Respiratory and Critical Care Medicine Volume 192 (2)238 – 248, July 2015.
  3. Richeldi L, du Bois RM, Raghu G, et al. for the INPULSIS® Trial Investigators. Efficacy and
    safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;380(22):2071-2082
  4. Cottin V, Taniguchi H, Richeldi L, et al. Effect of baseline emphysema on reduction in FVC decline with nintedanib in the INPULSIS® trials. Abstract presented at the 18th International Colloquium on Lung and Airway Fibrosis; Mont Tremblant, Canada, September 20-24, 2014. Available at: http://iclaf.com/conference/index.php/2014/ICLAF/paper/view/151. Accessed May 2016.
  5. Raghu G, Wells A, Nicholson AG, et al. Consistent effect of nintedanib on decline in FVC in patients across subgroups based on HRCT diagnostic criteria: results from the INPULSIS®trials in IPF. Poster presented at the 110th American Thoracic Society Conference; Denver, Colorado, May 15–20, 2015.
  6. Kolb M, Richeldi L, Kimura T, Stowasser S, Hallmann C, du Bois RM. Effect of baseline FVC on decline in lung function with nintedanib in patients with IPF: results from the INPULSIS® trials. Poster presented at the 110th American Thoracic Society Conference; Denver, Colorado, May 15–20, 2015.
  7. Costabel U, Inoue Y, Richeldi L, et al. Efficacy of nintedanib in idiopathic pulmonary fibrosis across pre-specified subgroups in INPULSIS®. AM J Respir Crit Care Med. 2015: doi:
  8. 1164/rccm.201503-05620C.
  9. Keating GM. Nintedanib: A Review of Its Use in Patients with Idiopathic Pulmonary Fibrosis. Drugs. 2015 Jul;75(10):1131-40. doi: 10.1007/s40265-015-0418-6.
  10. Hilberg F, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774-4782.
  11. Richeldi L., et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011 Sep 22;365(12):1079-87. doi: 10.1056/NEJMoa1103690.
  12. Selman M, et al. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med. 2001;134:136-51.
  13. Wollin L, et al. Antifibrotic and Anti-inflammatory Activity of the Tyrosine Kinase Inhibitor Nintedanib in Experimental Models of Lung Fibrosis. J Pharmacol Exp Ther. 2014;349:209–220.
  14. Ley B., et al. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 Feb 15;183(4):431-40. doi: 10.1164/rccm.201006-0894CI. Epub 2010 Oct 8.
  15. Nalysnyk L., et al. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev. 2012;21(126):355-361.
  16. Data on file. Boehringer Ingelheim. Worldwide prevalence 2016.
  17. NHLBI, NIH. What Is Idiopathic Pulmonary Fibrosis? Accessed at:www.nhlbi.nih.gov/health/health-topics/topics/ipf/ Accessed May 2016.
  18. Pulmonary Fibrosis Foundation. Symptoms. Available at: http://www.pulmonaryfibrosis.org/life-with-pf/about-pf. Accessed May 2016.

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
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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.

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