Data at ERS further demonstrates efficacy of once-daily Ultibro Breezhaler (QVA149) and Seebri Breezhaler (glycopyrronium bromide)

1 Data at ERS further demonstrates efficacy of once-daily Ultibro® Breezhaler® (QVA149) and Seebri® Breezhaler® (glycopyrronium bromide)  New analyses in the IGNITE clinical trial program showed that QVA149 provided superior, rapid and sustained improvements in lung function and significantly reduced shortness of breath versus comparator therapies1,2  BLAZE study also demonstrated significant improvements in shortness of breath with QVA149 compared to tiotropium 18 mcg in patients with moderate-to-severe COPD3  SPARK study showed similar rates of reduction in exacerbations with once-daily Seebri® Breezhaler® (glycopyrronium bromide) and open-label tiotropium 18 mcg in patients with severe-to-very severe COPD4,5 Tokyo, Japan – 9 September 2013: Sosei Group Corporation (“Sosei”; TSE Mothers Index: 4565) highlights that further data from the Novartis once-daily chronic obstructive pulmonary disease (COPD) clinical trial programs were presented by Novartis at the European Respiratory Society (ERS) Congress. The new analyses of data for once-daily Ultibro ® Breezhaler® (investigational QVA149 - indacaterol 85 mcg/glycopyrronium 43 mcg del ivered dose, equivalent to 110 mcg/50 mcg metered dose per capsule), showed signi ficant improvements in lung function, shortness of breath and health-related quality of life for chronic obstructive pulmonary disease (COPD) patients versus all comparators1,2. First results from a pooled analysis of 4,891 COPD patients in the IGNITE clinical trial program (SHINE, ILLUMINATE and SPARK st udies) showed that QVA149 provided superior, rapid and sustained improvements in lung function, and significantly reduced shortness of breath, compared to placebo, once-daily indacaterol maleate 150 mcg, glycopyrronium 50 mcg, open-label (OL) tiotropium 18 mcg and twice-daily salmeterol/fluticasone fixed dose combination (FDC SFC) 50 mcg/500 mcg 1,2. These improvements were maintained throughout the duration of the trials1,2. A new evaluation of patients with moderate-to-severe COPD from the BLAZE study showed that QVA149 provided significant improvements in patient-reported shortness of breath compared to tiotropium 18 mcg3. In addtition, clinical data for Seebri ® Breezhaler® (glycopyrronium bromide) presented at ERS included effi cacy and safety results from the SPARK study 4,5. At Week 64, once- daily glycopyrronium 50 mcg showed similar efficacy to OL tiotropium 18 mcg in 2 reducing the rate of exacerbations, improving lung function and health-related quality of life, and reducing rescue medication use in patients with severe-to-very severe COPD4. In analyses from the SPARK study, glycopyrronium 50 mcg (via Breezhaler ®) showed a safety profile in patients with severe-to-very severe COPD that was similar to OL tiotropium 18 mcg (via HandiHaler®)5. These results build upon the data previously presented from the glycopyrronium bromide Phase III GLOW trials and provide further evidence for Seebri ® Breezhaler® as a once- daily LAMA option for COPD patients. -Ends- Enquiries: Sosei Group Corporation Tokyo Office London Office Milica STOJKOVIC, Investor Relations Kathryn LYDON, PA to CEO & Corporate Communication +81-(0)3-5210-3399 +44-(0)20-7691-0983 [email protected] [email protected] About QVA149 Investigational QVA149 is a Fixed-Dose Combination (FDC) of two bronchodilators, Onbrez® Breezhaler ® (indacaterol maleate), a long-acting beta 2-adrenergic agonist (LABA) and Seebri ® Breezhaler ® (glycopyrronium bromide), a long-acting muscarinic antagonist (LAMA). Both are currently used by healthcare professionals as individual therapies to treat COPD. QVA149 received a positive opinion for approval from the European Medicine Agency’s (EMA) Committee for the Human use of Medicinal Products (CHMP) in July 2013 as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. QVA149 also gained endorsement for approval in August from the Drug Committee of MHLW (Ministry of Health, Labour and Welfare) for the treatment of COPD in Japan. About the IGNITE clinical trial program In the Phase III IGNITE clinical trial program, QVA149 is being investigated for the treatment of COPD patients as an inhaled, once-daily, FDC of indacaterol maleate and glycopyrronium bromide. IGNITE is 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 8-20. The first eight studies (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK, BLAZE, AR ISE, BEACON) completed in 2012. The studies are designed to investigate the efficacy, safety and tolerability, lung function, exercise endurance, exacerbations, shortness of breath and quality of life in patients treated with QVA149. Results from the Phase III IGNITE trials 8-18 demonstrated statistically significant improvements in bronchodilation with QV A149 versus comparator treatments widely used as current standards of care 21. Data showed that QVA149 significantly improved 3 bronchodilation compared to OL tiotropium 18 mcg, SFC 50 mcg/500 mcg, indacaterol maleate 150 mcg, glycopyrronium 50 mcg an d placebo providing a rapid onset within five minutes, and sustained bronchodilation during a 24 hour period which was maintained for up to 26 weeks 22. In the IGNITE Phase III trial program, QVA149 also showed symptomatic improvements versus placebo in COPD patients 8,9,11,21. These symptomatic improvements included shortness of breath, exercise tolerance, rescue medication use and health-related quality of life8,9,11,21. 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, SFC 50 mcg/500 mcg) in the incidence of adverse and serious adverse events8,9,10,11,22. *Total refers to all 11 IGNITE studies. About Seebri® Breezhaler® Once-daily Seebri® Breezhaler® (glycopyrronium bromide) is a novel inhaled long-acting muscarinic antagonist (LAMA; also referred to as a long-acting anticholinergic) indicated as a maintenance bronchodilator treatment to re lieve symptoms in adult patients with COPD23. Glycopyrronium bromide was exclusively licensed to Novartis in April 2005 by Sosei and its co-development partner Vectura. Phase III data from the GLOW 1, 2 and 3 studies demonstrated that glycopyrronium 50 mcg delivered rapid and significant sustained improvements in lung function (measured by mean FEV 1) from Day 1 compared with placebo and sustained this for 24 hours over 52 weeks, and significantly improved exercise endurance versus placebo 24-26. Seebri ® Breezhaler ® is approved in the EU/EEA, Japan, Switzerland, Canada, Australia and a number of other countries. All Novartis inhaled COPD portfolio pr oducts 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 limitation 27. The Breezhaler ® device allows patients to hear, feel and see that they have taken the full dose correctly23. Seebri®, Ultibro® and Breezhaler® are registered trademarks of Novartis. 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 life 7,28. It affects an estimated 210 million people worldwide and is projected to be the third leading cause of death by 2020 6. 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 retirement and reductions in workforce participation29. 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. 4 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. Vogelmeier C et al. Once-daily QVA149 provides clinically meaningful improvements in lung function and clinical outcomes. [ERS abstract 851178; Session 82; Date: September 8, 2013 Time: 12:50-14:40]. 2. 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 abstract 851388; Session 346; Date: September 10 2013 Time: 8:30-10:30]. 3. Mahler D et al. Once-daily QVA149 demonstrates superior improvements in patient-reported dyspnea compared to tiotropium in patients with moderate-to-severe COPD: the BLAZE study. [ERS abstract 851284; Session 369; Date: September 10 2013 Time: 10:45-12:45]. 4. Wedzicha JA et al. Once-daily glycopyrronium improves lung function and reduces exacerbations in severe-to-very severe COPD patients: the SPARK study. [ERS abstract 851270; Session 41; Date: September 8, 2013 Time: 8:30- 10:30]. 5. Decramer M et al. Safety of once-daily glycopyrronium in patients with severe-to-very severe COPD: the SPARK study. [ERS abstract 851279; Session 346; Date September 10, 2013 Time: 8:30-10:30]. 6. Global Alliance Against Chronic Respiratory Diseases (G ARD). Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach. Available at: http://www.who.int/gard/publications/GARD%20Book%202007.pdf. [Accessed 3 September 2013]. 7. 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 3 September 2013]. 8. 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 Respir Med 2013 http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(13)70052-3/abstract [Accessed 3 September 2013]. 9. Beeh et al. QVA149 once daily improves exercise tolerance and lung function in patients with COPD: the BRIGHT study. [BTS Winter Meeting 2012, Poster presentation P191; Date: 6 December; Time: 16:00-17:30]. 10. 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. 11. Bateman ED et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. European Respiratory Journal http://erj.ersjournals.com/content/early/2013/05/30/09031936.00200212.full.pdf. [Accessed 3 September 2013]. 12. Dahl et al. 2012. QVA administered once daily provides significant improvements in lung function over 1 year in patients with COPD: The ENLIGHTEN study. Volume abstract 853405. 13. 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]. 14. 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 3 September 2013]. 15. 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] Available at: www.clinicaltrials.gov/ct2/show/NCT01529632?term=BEACON&rank=6. [Accessed 3 September 2013]. 5 16. 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 3 September 2013]. 17. 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. [Online]. Available at: www.clinicaltrials.gov/ct2/show/NCT01709903?id=01709903&rank=1. [Accessed 3 September 2013]. 18. ClinicalTrial.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 3 September 2013]. 19. FDA Access Data, n.d. Spiriva Medical Review Part 2. [Online] Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-395_Spiriva.cfm. [Accessed 3 September 2013]. 20. FDA Access Data, 2003. Advair Medical Review. [Online] Available at: www.accessdata.fda.gov/drugsatfda_docs/nda/2003/021077_S003_ADVAIR_DISKUS.pdf. [Accessed 3 September 2013]. 21. 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]. 22. Welte T et al. QVA149 once daily is safe and well tolerated in patients with COPD: the SHINE study. [ATS abstract 41616; Session A43; Date: May 19, 2013, 8:15-16.30]. 23. 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/WC5001337 69.pdf. [Accessed 3 September 2013]. 24. 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. 25. 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. 26. 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. 27. 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. 28. Joshi M et al. Symptom burden in chronic obstructive pulmonary disease and cancer. Obstructive, occupational and environmental diseases. 2012;18(2). 29. 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.

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