Footnotes* Combined figures for HandiHaler® and Respimat®

** Respimat® delivers a metered dose of medication in a mist at the push of a button requiring just a slow deep breath from a patient

Spiolto® Respimat® (tiotropium/olodaterol) is Boehringer Ingelheim’s new advance in COPD maintenance therapy.

The clinical course of COPD and the TOviTO® clinical trial programme

Spiolto® Respimat® provides significant improvements in lung function, breathlessness, quality of life and reduction of rescue medication use over Spiriva® Respimat®, right from the initial stages when patients need maintenance therapy.1

Spiolto® is administered via Respimat®, which actively** delivers a unique mist, meaning the patient just needs to take a slow deep breath.2-8

In COPD, decreasing lung function causes breathlessness and leads to a downward spiral of reduced physical activity, worsening symptoms and further inactivity.9 Decreasing exercise capacity reduces quality of life and increases the risk of disability and death.10

The >15,000 patient TOviTO® Phase III clinical trial programme has been designed to evaluate the effect of Spiolto® Respimat® on many of these important elements in the clinical course of COPD.

Spiolto® Respimat®

enhanced by Striverdi® (olodaterol) which was specifically designed to complement the efficacy of Spiriva®

Spiolto® Respimat® fact sheet

built on tiotropium, the active ingredient in Spiriva® HandiHaler® and Spiriva® Respimat® - the world’s most prescribed COPD maintenance treatment with over 40 million patient-years* of real life experience across all COPD severities

Spiolto® Respimat® fact sheet

Efficacy and safety results from TONADO® 1&2: the pivotal Phase III trials for Spiolto® Respimat®

Data from the pivotal Phase III TONADO® trials show Spiolto® Respimat® provides1*…

…consistent improvements in lung function over Spiriva® Respimat®

…a comparable safety profile to tiotropium or olodaterol alone

…significant improvements in quality of life over Spiriva® Respimat®

...significant improvements in breathlessness over Spiriva® Respimat®

Quality of life (measured using the St George‘s Respiratory Questionnaire, SGRQ)

Dsypnea (measured using transition dyspnea index, TDI)

…reduction in the use of rescue medication over Spiriva® Respimat®

night-time26%22%

day-time

Reductionin rescue

medication

TDI f

ocal

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)

Tiotropium/olodaterol 5/5 μg Tiotropium 5 μg Olodaterol 5 μg

48.7

SGRQ

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Tiotropium/olodaterol 5/5 μg Tiotropium 5 μg Olodaterol 5 μg

Responder rates (%)†Change from baseline

TDI f

ocal

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)

Tiotropium/olodaterol 5/5 μg Tiotropium 5 μg Olodaterol 5 μg⊕

Footnotes* After 24 weeks† Responder=a decrease in SGRQ total score at week 24 of ≥ 4.0 units from baseline

Adjusted mean FEV1 AUC0–3 response (i.e. change from baseline)

Adjusted mean trough FEV1 response (i.e. change from baseline)

00 6 12 18 24 30

60ml

90ml

120ml

150ml

180ml

210ml

240ml

270ml

300ml

330ml

110mlimprovement vs. tiotropium

128mlimprovement vs. olodaterol

Tiotropium/olodaterol 5/5 μgTiotropium 5 μgOlodaterol 5 μg

00 6 12 18 24 30

0ml

20ml

40ml

60ml

80ml

100ml

120ml

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60mlimprovement vs. tiotropium

85mlimprovement vs. olodaterol

Tiotropium/olodaterol 5/5 μgTiotropium 5 μgOlodaterol 5 μg

Spiolto® Respimat® fact sheet

The importance of immediate COPD management

Further data from TONADO®1&2

Footnotes ‡ Figure adapted from Tantucci C, Modina D. Int J Chron Obstruct Pulmon Dis 2012 § Improvement in trough FEV1 after 24 weeks of treatment ¶ Results are derived from a post-hoc subgroup analysis of patients by GOLD stages in the TONADO® 1&2 studies (combined dataset). The primary endpoints of the TONADO® studies were: FEV1 AUC0–3, trough FEV1 and SGRQ total score in patients with a history of moderate-to-very severe COPD (GOLD 2–GOLD 4). References1. Buhl R, Maltais F, Abrahams R, et al. Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD2-4). Eur Respir J 2015; 45(4):969-79. 2. Newman SP, Brown J, Steed KP, Reader SJ, Kladders H. Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: Comparison of Respimat® with conventional metered-dose inhalers with and without spacer devices. Chest 1998; 113: 957-963. 3. Pitcairn G, Reader S, Pavia D, Newman S. Deposition of corticosteroid aerosol in the human lung by Respimat® Soft Mist™ Inhaler compared to deposition by metered dose inhaler or by Turbuhaler® dry powder inhaler. J Aerosol Med 2005; 18(3): 264-272. 4. Peterson JB, Prisk GK, Darquenne C. Aerosol deposition in the human lung periphery is increased by reduced-density gas breathing. J Aerosol Med Pulm Drug Deliv. 2008; 21(2): 159–168. 5. Dalby R, Spallek M, Voshaar T. A review of the development of Respimat® Soft Mist™ Inhaler. Int J Pharm 2004; 283: 1-9. 6. Zierenberg B. Optimising the in vitro performance of the Respimat®. J Aerosol Med 1999; 12 (Suppl 1): S19-S24. 7. Dalby RN, Eicher J, Zierenberg B. Development of Respimat® SoftMist™ inhaler and its clinical utility in respiratory disorders. Med Devices (Auckl) 2011; 4: 145-155. 8. Anderson P. Use of Respimat® Soft Mist™ Inhaler in COPD patients. Int J Chron Obstruct Pulmon Dis. 2006:1(3) 251–259. 9. Reardon JZ, Lareau SC, ZuWallack R. Functional status and quality of life in chronic obstructive pulmonary disease. Am J Med 2006; 119 (10 Suppl 1): 32-7. 10. Casaburi R. Activity promotion: a paradigm shift for chronic obstructive pulmonary disease therapeutics. Am Thorac Soc 2011; 8(4):334-7. 11. Mapel DW, et al. Severity of COPD at initial spirometry-confirmed diagnosis: data from medical charts and administrative claims. Int J COPD 2011:6 573–581 12. Tantucci C, Modina D. Lung function decline in COPD. Int J Chron Obstruct Pulmon Dis 2012; 7:95-9. 13. Buhl R, Abrahams R, Grönke L, et al. Tiotropium Plus Olodaterol Fixed-Dose Combination Therapy Provides Lung Function Benefits when Compared with Tiotropium Alone, Irrespective of Prior Treatment with a Long-Acting Bronchodilator: Post Hoc Analyses Of Two 1-Year Studies. ATS 2015 congress Abstract 64799 14. Korn S, Buhl R, Grönke L, et al. Analysis of the Efficacy and Safety of the Fixed-Dose Combination of Tiotropium + Olodaterol in Patients with COPD by Initial Disease Severity. ATS 2015 congress Abstract 64575

ERS 2015 abstract information: 1. D. Singh, Tiotropium + olodaterol fixed-dose combination shows clinically meaningful improvements in quality of life versus placebo. Poster PA2958 presented at the European Respiratory Society International Congress, Amsterdam, Monday, 28 September 2015, 14:45-16:45. 2. K.M. Beeh, ENERGITO: efficacy and safety of once-daily combined tiotropium + olodaterol versus twice-daily combined fluticasone propionate + salmeterol. Poster PA4366 presented at the European Respiratory Society International Congress, Amsterdam, Tuesday, 29 September 2015; 12:50-14:40

A post-hoc analysis shows that Spiolto® Respimat® more than doubles the improvement in lung function§ compared to Spiriva® Respimat® in patients who had no prior long-acting bronchodilator (LABD) at baseline13 ¶

For more media information on Boehringer Ingelheim’s respiratory portfolio visit: newscentre.boehringer-ingelheim.com

Current data indicate that at GOLD stage 2, lung function decline is steeper than in more severe stages12

When the majority of patients first go to see their doctor, their disease has already progressed to stages when they need maintenance treatment

GOLD 1

GOLD 2

GOLD 3

GOLD 4

26%

5% 19%

50%

GOLD 1

GOLD 2

GOLD 3

GOLD 4

26%

5% 19%

50%

GOLD 1

GOLD 2

GOLD 3

GOLD 4

26%

5% 19%

50%

Annual rate of decline in FEV1 by level of airway

obstruction‡

30% have severe/very severe disease (GOLD stage 3/4)11

50% have moderate

COPD (GOLD stage 2)

Optimal management right from the start of maintenance therapy may give patients the best opportunity to manage their symptoms, stay active and avoid the downward spiral of COPD for as long as possible

106%improvement

Trou

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GOLD 2-4 (moderate to severe) LABD naive

Tiotropium/olodaterol 5/5 μgTiotropium 5 μg

Improvement in trough FEV1 after 24 weeks of treatment in patients with no prior long-acting

bronchodilator treatment