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* The indication accepted by the EU regulatory authorities is for Spiriva® Respimat® as an add-on maintenance bronchodilator treatment in adult patients with asthma who are currently treated with the maintenance combination of inhaled corticosteroids (≥800 µg budesonide/day or equivalent) and long-acting ß

2 agonists and who experienced one

or more severe exacerbations in the previous year † at least inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) therapy± Severe asthma exacerbations were predefined in the clinical trial protocol as all asthma exacerbations that required

treatment with systemic (including oral) corticosteroids for at least 3 days, or, in case of ongoing and pre-existing systemic corticosteroid therapy, that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days

• In August 2014, a new indication for Spiriva® (tiotropium) Respimat®* in asthma was accepted by regulatory authorities in the EU

• Spiriva® Respimat®* is indicated as an add-on maintenance bronchodilator treatment in adult patients with asthma who are currently treated with the maintenance combination of inhaled corticosteroids (≥800µg budesonide/day or equivalent) and long-acting beta2-agonist and who experienced one or more severe exacerbations in the previous year

• Spiriva® (tiotropium) is an inhaled long-acting, anticholinergic bronchodilator. There are currently no other long-acting anticholinergic bronchodilators indicated for the treatment of asthma

About Spiriva® (tiotropium) Respimat®* in asthma

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4 key facts:

New asthma indication in the EU*

Significantly improves asthma symptoms (patients were 68% more likely to improve asthma control)

Significantly reduces risk of severe asthma exacerbations± by 21% - for patients with symptoms on current standard treatment†

Delivered via the Respimat® inhaler: allowing gentle inhalation2-4 that makes it easy for patients to take their therapy

2014

IMPROVES

ASTHMASYMPTOMS

REDUCES

THE RISK OF EXACERBATIONS

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• Pivotal, Phase III study results from the PrimoTinA-asthma® large-scale, Phase III clinical trials which investigated adults with asthma who continued to have symptoms despite taking at least ICS/LABA therapy, demonstrated that the addition of Spiriva® Respimat®:

• Significantly improved asthma symptoms

– patients were 68% more likely to improve asthma control5

• Reduced the risk of patients having a severe asthma exacerbation by a fifth (21%)1

– reducing the number of patients who experienced a severe asthma exacerbation1

• Reduced the risk of a patients’ asthma worsening by nearly one third (31%)1

• Delayed the time to patients’ first severe asthma exacerbation and first episode of asthma worsening1

• The safety of Spiriva® Respimat® has been shown to be balanced as compared to placebo1

• Spiriva® is delivered by the Respimat® Soft Mist™ Inhaler (SMI). Respimat® is the only inhaler delivering a slow-moving Soft Mist™ allowing gentle inhalation – making it easy for patients with asthma to take their therapy2-4

Kerstjens et al. NEJM 2012;367:1198-1207.HR, hazard ratio; ICS, inhaled corticosteroid; LABA, long-acting ß

2-agonist; OR, odds ratio Patients on at least ICS+LABA

Significant reduction in time to first severe asthma exacerbation - pooledPhase III

Patients at riskPlacebo Respimat®

Tiotropium Respimat®

Add-on to ICS+LABA

50

40

30

20

10

0

0 25 50 75 100 125 150 175 200 225 250 275 300 325

454 435 412 388 379 367 356 339 332 319 303 290 282 272

453 430 409 401 389 378 363 353 348 339 331 319 308 298

Time (days)

Pati

en

ts w

ith

at

least

on

e s

eve

re

ast

hm

a e

xace

rbati

on

(%

)

Tiotropium Respimat® n=122 (26.9%), Placebo Respimat® n=149 (32.8%)

Tiotropium Respimat®: 282 days; Placebo Respimat®: 226 days (25th percentile)

Number needed to treat: 15

Placebo Respimat®

Tiotropium Respimat®

HR=0.79; Risk reduction of 21% (P=0.03)

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Designed to evaluate efficacy and safety of Spiriva® Respimat® in asthma added on to at least ICS therapy

Consists of 18 studies

UniTinA-asthma® clinical trial programme

• UniTinA-asthma®: a comprehensive Phase II and III clinical trial programme designed to evaluate the efficacy and safety of Spiriva® Respimat® in patients with asthma

• Includes 18 clinical studies investigating Spiriva® Respimat® added to usual care in adults, adolescents and children (age 1+) with asthma across asthma severities

Involved more than 6,000 patients

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3 key facts:

18

SAFETY

EFFICACYx1000

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Almost one in two patients with asthma still experience asthma symptoms6-8

Symptomatic asthma patients have ~x6 greater chance of having an asthma attack in the next few weeks than those with minimal to no daytime symptoms9

About asthma and the unmet need for innovative treatments in asthma

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• The goal of asthma therapy is to achieve and maintain clinical control, which includes improving lung function, and reducing symptoms and exacerbation risk

• The current standard treatment for asthma includes inhaled corticosteroids (ICS), which treat the underlying inflammation. Long-acting beta2-agonists (LABA) bronchodilators may be prescribed in addition to ICS to prevent or relieve symptoms

• Despite current treatment options, almost one in two patients with asthma still experience asthma symptoms and may experience frightening and life-threatening asthma exacerbations6-8

• People suffering from asthma experience recurrent episodes of wheezing, breathlessness, chest tightness and coughing. These episodes may be punctuated by periods of more severe and sustained deterioration of symptoms, termed an asthma exacerbation10

• Asthma can, and does, still kill and many of these deaths may be preventable

• According to the GINA guidelines an estimated 300 million people worldwide have asthma10 – ~30 million people in Europe have asthma11

Words people with asthma use to describe how they feel

3 key facts:

EMBARRASSED

IN THE SHADOWOF ASTHMA

ANXIETY

UNCERTAIN

BLAMED

FEAR

~x 6

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References

1. Kerstjens HAM, Engel M, Dahl R et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 2012; 367 (13): 1198-1207

2. Dhand R. Aerosol plumes: slow and steady wins the race. J Aerosol Med 2005; 18 (3): 261-263

3. Hochrainer D, Hölz H, Kreher C, et al. Comparison of aerosol velocity and spray duration of Respimat® Soft Mist™ inhaler and pressurized metered dose inhalers. J Aerosol Med 2005; 18 (3): 273-282

4. Kardos P, Golisch W, Wolf K. New Soft MistTM Inhaler is effective and easy to use in patients with asthma and COPD. Eur Respir J 2005; 26 (Suppl 49): 338s

5. Boehringer Ingelheim. Data on file

6. Bateman ED, Boushey HA, Bousquet J, et al; GOAL Investigators Group. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004; 170 (8): 836-44

7. Partridge MR, Dal Negro RW, Olivieri D, et al. Understanding patients with asthma and COPD: insights from a European study. Prim Care Respir J 2011; 20 (3): 315-323

8. Demoly P, Paggiaro P, Plaza V, et al. Prevalence of asthma control among adults in France, Germany, Italy, Spain and the UK. Eur Respir Rev 2009; 18: (112): 105–112

9. Bateman ED, Reddel HK, Eriksson G, et al. Overall asthma control: the relationship between current control and future risk. J Allergy Clin Immunol. 2010; 125(3): 600-8

10. Global Initiative for Asthma (GINA). Pocket Guide for Asthma Management and Prevention. Available at: http://www.ginasthma.org/documents/1/Pocket-Guide-for-Asthma-Management-and-Prevention [last accessed 01/07/14]

11. European Respiratory Society (ERS). European Lung White Book. Available at: http://www.erswhitebook.org/chapters/adult-asthma/ [last accessed 30/07/14]