The document describes a phase III clinical trial investigating the efficacy and safety of nintedanib in treating progressive fibrosing interstitial lung disease (PF-ILD), as nintedanib has shown efficacy in treating idiopathic pulmonary fibrosis and may also be effective for other progressive fibrosing ILDs by inhibiting lung fibrosis; the double-blind, randomized, placebo-controlled trial will enroll approximately 600 patients with PF-ILD across various countries and evaluate whether nintedanib can reduce the decline in lung function compared to placebo at 52 weeks.

1. Progressive Fibrosing Interstitial
Lung Disease (PF-ILD)
SC-CRP-00379 /
DE/OFE-181203
Disclaimer:
Nintedanib is an investigational compound in progressive fibrosing interstitial lung diseases other
than IPF and is currently not approved for the treatment of progressive fibrosing interstitial lung
diseases other than IPF!
These slides are intended for education and scientific information only!

2. Interstitial lung disease (ILD)
• ILD encompasses >200 lung disorders
*Not an established clinical diagnosis.
1. ATS/ERS. Am J Respir Crit Care Med 2002;165:277-304.
2. Travis WD et al. Am J Respir Crit Care Med 2013;188:733-48.
Idiopathic Interstitial
Pneumonias (IIPs)1,2
Idiopathic Pulmonary
Fibrosis (IPF)
Idiopathic Non-Specific
Interstitial Pneumonia
(iNSIP)
Respiratory
Bronchiolitis- Interstitial
Lung Disease
Desquamative Interstitial
Pneumonia
Cryptogenic Organising
Pneumonia
Acute Interstitial
Pneumonia
Hypersensitivity
Pneumonitis (HP)
Autoimmune ILDs
Rheumatoid Arthritis
ILD (RA-ILD)
Sjögren’s Syndrome
ILD
Systemic Lupus
Erythematous ILD
Polymyositis and
Dermatomyositis ILD
Mixed Connective
Tissue Disease ILD
Systemic Sclerosis
ILD (SSc-ILD)
Other Connective
Tissue Disease ILDs
Sarcoidosis Other ILDs
ILD
Idiopathic Lymphoid
Interstitial Pneumonia
Idiopathic
Pleuroparenchymal
Fibroelastosis
Unclassifiable IIPs
Interstitial
Pneumonia with
Autoimmune
Features (IPAF)*
• Lymphangioleiomyomatosis (LAM)
• Langerhans Cell Histiocytosis (LCH)
• Drug-Associated ILD
• Other Exposure ILDs
• Vasculitis/Granulomatosis ILDs
• Other Rare ILDs

3. Types of ILD most likely to have a progressive fibrosing
phenotype
Idiopathic Interstitial
Pneumonias (IIPs)1,2
Idiopathic Pulmonary
Fibrosis (IPF)
Idiopathic Non-Specific
Interstitial Pneumonia
(iNSIP)
Respiratory
Bronchiolitis- Interstitial
Lung Disease
Desquamative Interstitial
Pneumonia
Cryptogenic Organising
Pneumonia
Acute Interstitial
Pneumonia
Hypersensitivity
Pneumonitis (HP)
Autoimmune ILDs
Rheumatoid Arthritis
ILD (RA-ILD)
Sjögren’s Syndrome
ILD
Systemic Lupus
Erythematous ILD
Polymyositis and
Dermatomyositis ILD
Mixed Connective
Tissue Disease ILD
Systemic Sclerosis
ILD (SSc-ILD)
Other Connective
Tissue Disease ILDs
Sarcoidosis† Other ILDs
ILD
Idiopathic Lymphoid
Interstitial Pneumonia
Idiopathic
Pleuroparenchymal
Fibroelastosis
Unclassifiable IIPs
Interstitial
Pneumonia with
Autoimmune
Features (IPAF)*
• Lymphangioleiomyomatosis (LAM)
• Langerhans Cell Histiocytosis (LCH)
• Drug-Associated ILD
• Other Exposure ILDs‡
• Vasculitis/Granulomatosis ILDs
• Other Rare ILDs
*Not an established clinical diagnosis. †Stage IV sarcoidosis only. ‡e.g. asbestosis, silicosis.

4. Progressive Fibrosing ILD (PF-ILD)
• Several patients with ILD develop a progressive fibrosing phenotype,
characterised by self-sustaining fibrosis and a deterioration in lung
function, with worsening of symptoms and quality of life
– The proposed terminology for this phenotype is progressive fibrosing ILD
(PF-ILD)

5. Phase III trial of nintedanib in
patients with PF-ILD
1199.247 (ClinicalTrials.gov NCT02999178; EudraCT 2015-003360-37)
Disclaimer:
Nintedanib is an investigational compound in progressive fibrosing interstitial lung diseases other
than IPF and is currently not approved for the treatment of progressive fibrosing interstitial lung
diseases other than IPF!
These slides are intended for education and scientific information only!
Flaherty KR, Brown KK, Wells AU, et al. Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial
of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Resp Res 2017;4:e000212. doi:10.1136/
bmjresp-2017-000212

6. Rationale for investigating nintedanib as a treatment for
PF-ILD
• Working hypothesis: in patients with PF-ILD, the response to lung
injury involves the development of fibrosis that becomes progressive,
self-sustaining and independent of the trigger
• PF-ILD is characterised by worsening respiratory symptoms, declining
lung function, resistance to immunomodulatory therapies and high
mortality
• Nintedanib inhibits fundamental processes in the pathogenesis of lung
fibrosis, irrespective of the trigger,1–4 and has proven efficacy and
safety in the treatment of IPF
• Based on the clinical and mechanistic parallels between IPF and other
types of PF-ILD, nintedanib may be effective in the treatment of PF-
ILD beyond IPF
1. Wollin L et al. J Pharmacol Exp Ther 2014;349:209-20. 2. Wollin L et al. Eur Respir J 2015;45:1434-45.
3. Huang J et al. Ann Rheum Dis 2016;75:883-90. 4. Redente EF et al. Am J Respir Crit Care Med 2016;193:A4170.

7. Design of trial of nintedanib in PF-ILD
R, randomisation.
*Visits to occur every 16 weeks until end of treatment. A follow-up visit will take place 4 weeks after discontinuation of trial medication.
Flaherty KR et.al., BMJ Open Resp Res 2017;4:e000212. doi:10.1136/ bmjresp-2017-000212

8. Key inclusion criteria
• Age ≥18 years
• Physician-diagnosed ILD with features of diffuse fibrosing lung disease of
>10% extent on HRCT, confirmed by central review
• Meeting ≥1 of these criteria for disease progression in the 24 months before
screening, despite treatment with (unapproved) medication used in clinical
practice to treat ILD:
– Relative decline in FVC ≥10% predicted
– Relative decline in FVC ≥5–<10% predicted and worsening respiratory symptoms
– Relative decline in FVC ≥5–<10% predicted and increasing extent of fibrotic
changes on chest imaging
– Worsening of respiratory symptoms and increasing extent of fibrotic changes on
chest imaging
• DLco ≥30 and <80% predicted
• FVC ≥45% predicted
Flaherty KR et.al., BMJ Open Resp Res 2017;4:e000212. doi:10.1136/ bmjresp-2017-000212

9. Primary and main secondary endpoints
Primary endpoint
• Annual rate of decline in FVC (mL/year) at week 52
– There will be two co-primary analysis populations: the first will comprise all
patients, the second will comprise patients with UIP-like fibrotic pattern
only on HRCT
Main secondary endpoints
• Change from baseline in K-BILD total score at week 52
• Time to first acute exacerbation of ILD or death over 52 weeks
• Time to death over 52 weeks
K-BILD, King’s Brief Interstitial Lung Disease Questionnaire.
Flaherty KR et.al., BMJ Open Resp Res 2017;4:e000212. doi:10.1136/ bmjresp-2017-000212

10. Participating countries and timelines
Estimated enrolment: 600
Study start date: January 2017
Estimated study completion date: November 2019
Participating countries: Argentina, Belgium,
Canada, Chile, China, France, Germany, Italy,
Japan, South Korea, Poland, Russia, Spain, UK,
USA
Flaherty KR et.al., BMJ Open Resp Res 2017;4:e000212. doi:10.1136/ bmjresp-2017-000212

11. Dr. Christian Geiß
MSL Respiratory Diseases // Boehringer Ingelheim
christiangeiss@boehringer-ingelheim.com
Boehringer Ingelheim Pharma GmbH & Co. KG
Binger Straße 173
55216 Ingelheim am Rhein
Mobil: +49 179 9104244
Telefon: +49 6132 77 83
Fax: +49 6132 72 83