Product Update - Ultibro® Breezhaler®

Vectura Group plc

New findings confirm Ultibro® Breezhaler® consistently more effective than Seretide®* in reducing COPD flare-ups across different patient groups

· Ultibro® Breezhaler® reduced rate of all COPD exacerbations across different patient sub-groups vs Seretide® in new analyses from FLAME study

· Analyses show that Ultibro® Breezhaler® lowered patients' need for rescue medication and had improved benefit-risk profile compared to Seretide®, with less evidence of systemic effects

· Sub-group analyses of FLAME and a retrospective large-scale study showing potential relationship between inhaled corticosteroid use and pneumonia are being shared at ERS 2016

Chippenham, UK - 5 September 2016: Vectura Group plc (LSE: VEC) ("Vectura"), an industry-leading inhaled airways disease focused business, confirms the announcement by our alliance partner Novartis that new analyses from the head-to-head FLAME study confirmed that Ultibro® Breezhaler® is a more effective option for patients at risk of chronic obstructive pulmonary disease (COPD) flare-ups (exacerbations) than Seretide®, across different patient sub-groups1-10. These findings are being presented at the 2016 European Respiratory Society (ERS) International Congress this week in London, UK.

In the new analyses, once-daily Ultibro® Breezhaler® 110/50 mcg demonstrated consistent reductions in the rate of all exacerbations (mild, moderate and severe)1, regardless of age, smoking status, exacerbation history, disease severity2, eosinophil levels (a type of white blood cells)3 and previous inhaled corticosteroid (ICS) use4,5, versus twice-daily Seretide® 50/500 mcg. Specifically, among patients with the severest forms of COPD**, Ultibro® Breezhaler® significantly reduced the rate of exacerbations and improved their health status versus the commonly used ICS/LABA*** combination6. In addition, patients using Ultibro® Breezhaler® needed less rescue medication during the day7.

New analyses presented at ERS 2016 also showed that, compared to Seretide®, Ultibro® Breezhaler® was associated with fewer systemic effects, namely impairment of adrenal function8, which regulates the natural production of hormones. Ultibro® Breezhaler® use has previously shown to be associated with significantly fewer cases of pneumonia than the ICS/LABA combination11.

Adding evidence to the need to reduce the risks of chronic ICS therapy, results of a large retrospective observational study involving >87,000 participants (with and without COPD) from Sweden are also being shared at ERS 201612. The ARCTIC study found that COPD patients were at greater risk of pneumonia than those without the disease, but that this risk was even higher for those taking an ICS (whether at a low or high dose)12. Even people without COPD that took an ICS increased their risk of pneumonia, further demonstrating their interrelationship12.

Novartis is presenting over 35 abstracts from across its broad respiratory portfolio at ERS 2016.

James Ward-Lilley, Vectura's CEO, commented:

"These new findings further demonstrate the superior efficacy of Ultibro® Breezhaler® versus Seretide® across a range of patient sub-groups and support its use as a steroid-free treatment option for COPD patients at risk of exacerbations. This, combined with the existing efficacy and safety profile of Ultibro® Breezhaler® further confirms our confidence in its outlook"

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Enquiries

About FLAME

FLAME is a randomized, double-blind, double-dummy, parallel-group, non-inferiority, active-controlled 52-week study involving 3,362 COPD patients and conducted at 356 sites across 43 countries11.

Results published in the New England Journal of Medicine11 confirmed that Ultibro® Breezhaler® (indacaterol/glycopyrronium bromide) 110/50 mcg met its primary endpoint (non-inferiority) and furthermore demonstrated superiority to Seretide® (salmeterol/fluticasone [SFC]) 50/500 mcg on the rate of all COPD exacerbations (mild/moderate/severe) over one year of treatment in COPD patients with a history of at least one exacerbation in the previous year. Against further secondary endpoints, Ultibro® Breezhaler® was also superior compared to SFC in reducing or improving the following11:

- Rate and time to first moderate or severe COPD exacerbation

- Time to first COPD exacerbation (mild/moderate/severe)

- Time to first severe COPD exacerbation

- Lung function (trough FEV1)

- Health-related quality of life (St. George's Respiratory Questionnaire)

FLAME is part of the IGNITE Phase III clinical trial program exploring Ultibro® Breezhaler® for the treatment of COPD.

About Ultibro® Breezhaler®

Ultibro® Breezhaler® (indacaterol/glycopyrronium bromide) 110/50 mcg is a once-daily LABA***/LAMA**** dual bronchodilator approved in the European Union (EU) as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD13. Clinical trials have shown that it offers statistically significant improvements in bronchodilation compared to treatments widely used as current standards of care, including SFC 50/500 mcg14-16 and open-label tiotropium (18 mcg). Ultibro® Breezhaler® is currently approved for use in over 90 countries worldwide, including countries within the EU and Latin America, Japan, Canada, Switzerland and Australia.

Glycopyrronium bromide and certain use and formulation intellectual property were exclusively licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei.

About COPD

Chronic obstructive pulmonary disease (COPD) affects an estimated 210 million people worldwide18 and is the third leading cause of death19. It is progressive (usually gets worse over time), and can be a life-threatening disease18,20. COPD makes it difficult to breathe, with symptoms that have a destructive impact on patients' function (i.e. activity limitation, decreased mobility) and quality of life18,20.

Exacerbations (disease flare-ups) are a sudden worsening of COPD symptoms that can be frightening for patients, causing distress, anxiety and the deterioration of quality of life21. COPD exacerbations are also associated with significant healthcare resource burden and costs22, particularly due to the frequent need for hospitalisation. Consequently, the prevention of exacerbations is an important goal in COPD management to improve long-term health status and conserve healthcare resources23.

About Vectura

Vectura, a FTSE250 company listed on the London Stock Exchange (LSE: VEC), is an industry-leading inhaled airways disease focused business with proprietary formulation and devices across DPI, pMDI and smart nebulisation platforms. With our extensive range of technologies, capabilities and collaborations, we believe we can become a leader in the development of inhalation products, increasing our ability to help patients suffering from respiratory diseases. In June 2016 Vectura completed a merger with Skyepharma PLC.

Vectura has seven inhaled, four non-inhaled and ten oral products marketed by partners with growing global royalty streams, and a portfolio of drugs in clinical development, a number of which have licence agreements with several global pharmaceutical and biotechnology companies including Hikma, Novartis, Sandoz, Mundipharma, Kyorin, Baxter, GSK, UCB, Ablynx, Grifols, Chiesi, Almirall, Janssen, and Tianjin KingYork.

For further information, please visit Vectura's website at www.vectura.com.

Notes

* Seretide® Accuhaler®/Diskus® are registered trademarks of the GlaxoSmithKline group of companies

** GOLD Group D

*** a long-acting beta2-adrenergic agonist

**** a long-acting muscarinic antagonist

References

1. Wedzicha J, Vogelmeier CF, Ayers T et al. Once-daily indacaterol/glycopyrronium (IND/GLY) reduces all exacerbations compared with twice-daily salmeterol/fluticasone (SFC) in COPD patients with ≥1 exacerbation in the previous year: the FLAME study. [ERS 2016 abstract 852871; Session 183; Date: September 4, 2016 Time: 12:50-14:40].

2. Wedzicha J, Chapman KR, FowlerTaylor A et al. Indacaterol/glycopyrronium (IND/GLY) reduces exacerbations compared with salmeterol/fluticasone (SFC) in various subgroups from the FLAME study. [ERS 2016 abstract 852899; Session 183; Date: September 4, 2016 Time: 12:50-14:40].

3. Chapman KR, Vogelmeier CF, FowlerTaylor A et al. Effect of indacaterol/glycopyrronium (IND/GLY) vs salmeterol/fluticasone (SFC) on moderate or severe COPD exacerbations and lung function based on baseline blood eosinophil counts: Results from the FLAME study. [ERS 2016 abstract 853471; Session 123; Date: September 4, 2016 Time: 08:30-10:30].

4. Patalano F, Wedzicha J, Vestbo J et al. Indacaterol/glycopyrronium (IND/GLY) reduces exacerbation and improves lung function versus salmeterol/fluticasone (SFC) in patients with and without prior ICS use: the FLAME study. [ERS 2016 abstract 852689; Session 183; Date: September 4, 2016 Time: 12:50-14:40].

5. Wedzicha J, Mezzi K, Timothy RA et al. Indacaterol/glycopyrronium (IND/GLY) reduces the risk of exacerbations versus salmeterol/fluticasone (SFC) in moderate-to-very severe COPD patients irrespective of prior ICS/LABA/LAMA therapy: the FLAME study. [ERS 2016 abstract; Session 695; Date: September 7, 2016 Time: 09:30].

6. Larbig M, Vogelmeier CF, Roche N et al. Efficacy of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) on exacerbations and health status in GOLD Group D COPD patients: the FLAME study. [ERS 2016 abstract 852867; Session 183; Date: September 4, 2016 Time: 12:50-14:40].

7. Fogel R, Chapman KR, Vogelmeier CF, et al. Once-daily indacaterol/glycopyrronium (IND/GLY) reduces use of rescue medication versus twice-daily salmeterol/fluticasone (SFC) in patients with moderate-to-very severe COPD: results from the FLAME study. [ERS 2016 abstract 852907; Session 183; Date: September 4, 2016 Time: 12:50-14:40].

8. Olsson P, Vogelmeier CF, Chapman KR et al. Effect of indacaterol/glycopyrronium versus salmeterol/fluticasone on hypothalamic pituitary-adrenal axis function in moderate-to very severe COPD patients: results from the FLAME study. [ERS 2016 abstract 853124; Session 183; Date: September 4, 2016 Time: 12:50-14:40].

9. Olsson P, Roche N, Vestbo J, et al. Cardiovascular (CV) safety of indacaterol/glycopyrronium (IND/GLY) compared with salmeterol/fluticasone combination (SFC) in moderate-to-very severe COPD patients with prior exacerbations: The FLAME study. [ERS 2016 abstract 853013; Session 123; Date: September 4, 2016 Time: 08:30-10:30].

10. Chapman KR, Roche N, Ayers T et al. Indacaterol/glycopyrronium (IND/GLY) is superior to salmeterol/fluticasone (SFC) in improving health status of patients with moderate-to-very severe COPD: Results from the FLAME study. [ERS 2016 abstract 852898; Session 183; Date: September 4, 2016 Time: 12:50-14:40].

11. Wedzicha JA, Banerji D, Chapman KR, et al. Indacaterol/Glycopyrronium Versus Salmeterol/Fluticasone for COPD Exacerbations. New England Journal of Medicine. 2016. Available at: www.nejm.org/doi/full/10.1056/NEJMoa1516385 [Accessed 29 July 2016].

12. Janson C, Johansson G, Ställberge B, et al. ICS and risk of pneumonia in Swedish COPD patients: The ARCTIC study. [ERS 2016 abstract; Session 593; Date: September 6, 2016 Time: 12:50-14:40]

13. Ultibro Breezhaler EU Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002679/WC500151255.pdf [Accessed 29 July 2016].

14. Vogelmeier C, et al. Once-daily QVA149 provides clinically meaningful improvements in lung function and clinical outcomes versus placebo, indacaterol, glycopyrronium, tiotropium and salmeterol/fluticasone in patients with COPD. [ATS abstract 40759; Session C45; Date: May 21, 2013 Time: 8:15 -10:45].

15. Vogelmeier C, et al. Once-daily QVA149 provides clinically meaningful improvements in lung function and clinical outcomes. [ERS 2013 abstract 851178; Session 82; Date: September 8, 2013 Time: 12:50-14:40].

16. Banerji D, et al. Dual bronchodilation with once-daily QVA149 improves dyspnea and health status and reduces symptoms and rescue medication use in patients with COPD: the IGNITE trials. [ERS 2013 abstract 851388; Session 346; Date: September 10, 2013 Time: 8:30-10:30].

17. Pavkov R, Mueller S, Fiebich K, et al. Characteristics of a capsule based dry powder inhaler for the delivery of indacaterol. CMRO. 2010;26; 11:2527-2533.

18. Global Alliance Against Chronic Respiratory Diseases (GARD). Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach. Available at: http://www.who.int/gard/publications/GARD_Manual/en/ [Accessed 29 July 2016].

19. World Health Organization: The top 10 causes of death fact sheet No 310. Available at: http://www.who.int/mediacentre/factsheets/fs310/en/ [Accessed 29 July 2016].

20. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated 2016. Available at: http://goldcopd.org/ [Accessed 29 July 2016].

21. Adams R, Chavannes N, Jones K, et al. Exacerbations of chronic obstructive pulmonary disease-a patients' perspective. Prim Care Respir J. 2006;15:2:102-109.

22. Toy EL, Gallagher K, Stanley E, et al. The economic impact of exacerbations of chronic obstructive pulmonary disease and exacerbation definition: a review. COPD. 2010;7:214-28.

23. Anzueto A. Impact of exacerbations on COPD. European Respiratory Review. 2010;19:116:113-118.

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Forward-looking statements

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