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Sosei Group Corporation (“Sosei”)(TOKYO:4565) confirms the information released today by Novartis announcing that the European Commission approved once-daily Ultibro^® Breezhaler^® (indacaterol 85 mcg / glycopyrronium 43 mcg) as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). Ultibro^® Breezhaler^® was developed under the name QVA149. The approval triggers a $10m milestone payment to Sosei.

Dual bronchodilation with QVA149 is expected to set a new standard of care in COPD by combining the proven efficacy and safety benefits of two established Novartis COPD treatments, the LABA*, Onbrez^® Breezhaler^® (indacaterol), and the LAMA**, Seebri^® Breezhaler^® (glycopyrronium bromide). Both these components are delivered through the Breezhaler^® inhalation device, as is QVA149, and are widely available in many countries around the world.

Last week, QVA149 was approved also in Japan and US submission is anticipated at the end of 2014.

The approval of QVA149 was based on the comprehensive IGNITE Phase III clinical trial program, one of the largest international trial programs in COPD comprising 11 studies in total with more than 10,000 patients from 52 countries^1-3,6-15. From the eight IGNITE studies which completed in 2012^{1-3, 6-10}, data showed that QVA149 significantly improved lung function versus several current standard treatments^1-3,6 and showed significant symptomatic improvements versus placebo in breathlessness, exercise tolerance, rescue medication use and health-related quality of life^1,2,6. QVA149 also demonstrated statistically significant symptomatic improvements in breathlessness, rescue medication use and health-related quality of life compared to open-label (OL) tiotropium 18 mcg¹. The rate of all COPD exacerbations (mild, moderate and severe) was significantly improved with QVA149 compared to glycopyrronium 50 mcg and OL tiotropium 18 mcg³.

In clinical studies, QVA149 demonstrated an acceptable safety profile with no meaningful differences between the treatment groups (placebo, indacaterol 150 mcg, glycopyrronium 50 mcg, OL tiotropium 18 mcg, salmeterol / fluticasone (SFC) 50 mcg / 500 mcg) in the incidence of adverse and serious adverse events^1-3,6. The safety profile was characterized by typical anticholinergic and beta-adrenergic effects related to the individual components of the combination^1-3,6-10.

Ultibro^®, Seebri^®, Onbrez^® and Breezhaler^® are registered trademarks of Novartis AG.

* a long-acting beta₂-adrenergic agonist, ** a long-acting muscarinic antagonist

About Ultibro^®

Ultibro^® Breezhaler^® (indacaterol / glycopyrronium) is an inhaled, once-daily, fixed-dose combination of the LAMA, glycopyrronium bromide and the LABA, indacaterol maleate and was developed under the name QVA149. QVA149 was investigated for the treatment of COPD in the Phase III IGNITE clinical trial program. IGNITE was one of the largest international clinical trial programs in COPD comprising 11 studies in total (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK, BLAZE, ARISE, BEACON, RADIATE, LANTERN, FLAME) with more than 10,000* patients across 52 countries^1-3,6-15. The first eight studies (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK, BLAZE, ARISE, BEACON) completed in 2012^1-3,6-10. The studies were designed to investigate efficacy (lung function, exercise endurance, exacerbations, shortness of breath and quality of life), safety and tolerability of patients treated with Ultibro^® Breezhaler^®1-3,6-13.

Results from the Phase III IGNITE trials have demonstrated statistically significant improvements in bronchodilation with QVA149 versus several treatments^1-3,6 widely used as current standards of care. Data showed that QVA149 significantly improved lung function compared to OL tiotropium 18 mcg, fixed dose combination SFC 50 mcg / 500 mcg, indacaterol maleate 150 mcg, glycopyrronium 50 mcg and placebo providing a rapid onset of action within five minutes, and sustained bronchodilation during a 24 hour period which was maintained for up to 26 weeks^2,6. In the IGNITE phase III trial program, QVA149 also showed symptomatic improvements versus placebo in COPD patients^1,2,6. These symptomatic improvements included breathlessness, exercise tolerance, rescue medication use and health-related quality of life^1,2,6. QVA149 also significantly improved the rate of all COPD exacerbations (mild, moderate and severe) compared to glycopyrronium 50 mcg and OL tiotropium 18 mcg³.

* Total refers to all 11 IGNITE studies.

About Seebri^® Breezhaler^®

Seebri^® Breezhaler^® (glycopyrronium bromide) is a once-daily inhaled long-acting muscarinic antagonist (LAMA; also referred to as a long-acting anticholinergic) indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD¹⁶. Glycopyrronium bromide was exclusively licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei. In Phase III studies (GLOW 1, 2 and 3), once-daily glycopyrronium 50 mcg demonstrated rapid improvements in lung function after first dose on Day 1 which were sustained for 24 hours and maintained over the 52 week study period compared with placebo^17-19. Glycopyrronium bromide 50 mcg also significantly improved shortness of breath, health-related quality of life, exacerbation risk, and exercise endurance versus placebo^17-19. Seebri^® Breezhaler^® is approved in the EU, Japan, Switzerland, Canada, Australia and a number of other countries.

All Novartis inhaled COPD portfolio products are being developed for delivery via a single-dose dry powder inhaler (SDDPI) called the Breezhaler^® device which has low air flow resistance, making it suitable for patients with airflow limitation²⁰. The Breezhaler^® device allows patients to hear, feel and see that they have taken the full dose correctly¹⁶.

About COPD

COPD is a progressive life-threatening disease that makes it hard to breathe, with symptoms that have a destructive impact on patients’ function and quality of life²¹. It affects an estimated 210 million people worldwide⁵ and is projected to be the third leading cause of death by 2020²¹. COPD is often considered to be a disease of later years, but estimates suggest that 50% of those with COPD are now less than 65 years old, resulting in increases in absenteeism, premature retirement²² and reductions in workforce participation^22,23.

About Sosei

Sosei is an international biopharmaceutical company anchored in Japan with a global reach. It practises a reduced risk business model by acquiring compounds from, and bringing compounds into, Japan through exploitation of its unique position within global markets.

For further information about Sosei, please visit www.sosei.com.

Forward-looking statements

This press release contains forward-looking statements, including statements about the discovery, development and commercialisation of products. Various risks may cause Sosei’s actual results to differ materially from those expressed or implied by the forward-looking statements, including: adverse results in clinical development programmes; failure to obtain patent protection for inventions; commercial limitations imposed by patents owned or controlled by third parties; dependence upon strategic alliance partners to develop and commercialise products and services; difficulties or delays in obtaining regulatory approvals to market products and services resulting from development efforts; the requirement for substantial funding to conduct research and development and to expand commercialisation activities; and product initiatives by competitors. As a result of these factors, prospective investors are cautioned not to rely on any forward-looking statements. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

References:

1. Bateman ED, Ferguson GT, Barnes N, et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. European Respiratory Journal [Published on May 30 2013]. doi: http://dx.doi.org/10.1183/09031936.00200212. [Accessed 12 September 2013].

2. Vogelmeier C et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol/fluticasone in patients with COPD (ILLUMINATE): a randomised, double-blind, parallel group study. Lancet Respiratory Medicine. 2013;1(1): 51-60.

3. Wedzicha JA et al. Analysis of Chronic Obstructive Pulmonary Disease Exacerbations with the Dual Bronchodilator QVA149 Compared with Glycopyrronium and Tiotropium (SPARK): a Randomized, Double-blind, Parallel-group Study. Lancet Respiratory Medicine 2013;1(3): 199-209.

4. European Federation of Allergy and Airways Diseases Patients Associations. Chronic Obstructive Pulmonary Disease. Available at: http://www.efanet.org/wp-content/uploads/2012/07/EFACOPDBook.pdf. [Accessed 18 September 2013].

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7. Dahl R et al. Safety and efficacy of dual bronchodilation with QVA149 in COPD patients: the ENLIGHTEN study. Respiratory Medicine Journal 2013;107:1558-1567.

8. Mahler D et al. Superior lung function with once-daily QVA149 translates into improvements in patient reported breathlessness compared with placebo and tiotropium in COPD patients: the BLAZE study. [ATS abstract 45308; Session C20; Date: May 21, 2013 Time: 8:15-10:45].

9. ClinicalTrials.gov, n.d. Long Term Safety and Tolerability of QVA149 Versus Tiotropium in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD) (ARISE). [Online] Available at: http://www.clinicaltrials.gov/ct2/show/NCT01285492?term=%28ARISE%29&rank=4. [Accessed 18 September 2013].

10. ClinicalTrials.gov, n.d. Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD) (BEACON). [Online]
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11. ClinicalTrials.gov, n.d. Comparison of Long-term Safety of the Combination Product QVA149A Against Placebo and Standard of Care Treatment in Chronic Obstructive Pulmonary Disease Patients With Moderate to Severe Airflow Limitation (RADIATE). [Online] Available at: www.clinicaltrials.gov/ct2/show/NCT01610037?term=GLISTEN&rank=1. [Accessed 18 September 2013].

12. ClinicalTrials.gov, n.d. A 26-week Treatment Randomized, Double-blind, Double Dummy, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of QVA149 (Indacaterol / Glycopyrronium Bromide) Compared to Fluticasone/Salmeterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease. (LANTERN) [Online]. Available at: www.clinicaltrials.gov/ct2/show/NCT01709903?id=01709903&rank=1. [Accessed 18 September 2013].

13. ClinicalTrials.gov, n.d. A 52-week Treatment, Multi-center, Randomized, Double-blind, Double Dummy, Parallel-group, Active Controlled Study to Compare the Effect of QVA149 (Indacaterol Maleate / Glycopyrronium Bromide) With Salmeterol/Futicasone on the Rate of Exacerbations in Subjects With Moderate to Very Severe COPD (FLAME). [Online] Available at: http://clinicaltrials.gov/ct2/show/NCT01782326?term=COPD+novartis+52&rank=2. [Accessed 18 September 2013].

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16. EMA. 2012. Seebri Breezhaler EU Summary of Product Characteristics. [Online] 17 October 2012. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002430/WC500133769.pdf. [Accessed 18 September 2013].

17. D’Urzo A et al. Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial. Respiratory Research 2011;12:156.

18. Kerwin E et al. Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: The GLOW2 study. Eur Resp J 2012;40(5):1106-1114.

19. Beeh K et al. Once-daily NVA237 improves exercise endurance from first dose in patients with COPD: the GLOW3 trial. Int J Chron Obstruct Pulmon Dis 2012;7:503-513.

20. Pavkov et al. Characteristics of a capsule based dry powder inhaler for the delivery of indacaterol. CMRO 2010; 26; 11:2527–2533. doi:10.1185/03007995.2010.518916.

21. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2013. http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html. [Accessed 18 September 2013].

22. Fletcher MJ et al. COPD Uncovered: An International survey on the impact of chronic obstructive pulmonary disease (COPD) on a working age population. BMC Public Health 2011;11:612.

23. daCosta M et al. The burden of chronic obstructive pulmonary disease among employed adults. Int J Chron Obstruct Pulmon Dis 2012;7:211-219. Published online 2012 March doi: 10.2147/COPD.S29280. [Accessed 18 September 2013].