1 LUX-Lung 3 clinical trial ECOG=Eastern Cooperative Oncology Group. Sequist LV et al. J Clin Oncol. 2013;31(27): Treatment-naïve Advanced NSCLC stage IIIB/IV adenocarcinoma EGFR M+ ECOG 0 or 1 Afatinib 40 mg oral once daily n=230 Pemetrexed/cisplatin 75 mg/m 2 / 500 mg/m 2 IV d1, q3w up to 6 cycles n=115 Median follow-up: For PFS: 16.4 months For OS: 41 months 2:1 randomisation LUX-Lung 3 is a multi-national, prospective, randomised, phase III trial of afatinib vs cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations

2 LUX-Lung 3 study endpoints Progression-free survival (PFS) by independent review EORTC=European Organisation for Research and Treatment of Cancer. Sequist LV et al. J Clin Oncol. 2013;31(27): Overall survival (OS) Objective response rate Disease control rate Duration of response Patient-reported outcomes, including symptom control and health-related quality of life as measured through EORTC questionnaires Primary endpoint Secondary endpoints included

3 Patient demographics and characteristics were well balanced between the 2 treatment arms * By American Joint Committee on Cancer, sixth edition. Sequist LV et al. J Clin Oncol. 2013;31(27): Afatinib (n=230) Pem/cis (n=115) Sex, n (%) Male83 (36.1)38 (33.0) Female147 (63.9)77 (67.0) Age, years, median (range) 61.5 (28-86)61.0 (31-83) Race, n (%) White61 (26.5)30 (26.1) Eastern Asian165 (71.7)83 (72.2) Other4 (1.7)2 (1.7) Smoking status, n (%) Never155 (67.4)81 (70.4) Former70 (30.4)32 (27.8) Current5 (2.2)2 (1.7) ECOG PS, n (%) 092 (40.0)41 (35.7) 1138 (60.0)73 (63.5) (0.9) Adenocarcinoma stage*, n (%) IIIB (with pleural effusion)20 (8.7)17 (14.8) IV210 (91.3)98 (85.2) EGFR mutation, n (%) Exon 19 deletion113 (49.1)57 (49.6) L858R91 (39.6)47 (40.9) Other26 (11.3)11 (9.6)

LUX-LUNG 3 Efficacy

Del9/L858R mutations 5 Afatinib significantly increased first-line PFS vs pemetrexed/cisplatin in common mutations (del19/L858R) ITT=intent to treat; PFS=progression-free survival. Sequist LV et al. J Clin Oncol. 2013;31(27): % reduction in relative risk of death or tumour progression in patients with common mutations (HR 0.47; P<0.001) In ITT population, median PFS was 11.1 and 6.9 months for afatinib and pemetrexed/ cisplatin, respectively (HR: 0.58; 95% CI, ; P<0.001) Progression-free survival (primary endpoint) LUX-Lung 3 preplanned subgroup analysis PFS rate (%) Time (months) Hazard ratio 0.47 (95% CI, ) P<0.001 Afatinib (n=204) Pemetrexed/cisplatin (n=104) 6.9 months 13.6

Del19 mutations 6 Afatinib achieved over 1 year extended OS vs pemetrexed/cisplatin in subgroup of del19 patients Hazard ratio 0.54 (95% CI, ) P= Afatinib (n=112) Pemetrexed/cisplatin (n=57) ITT=intent to treat; OS=overall survival. Yang JC et al. Lancet Oncol. 2015;16(2): % reduction in relative risk of death in del19 patients (HR 0.54; P=0.0015) OS in ITT population (N=345) was 28.2 and 28.2 months for afatinib vs pemetrexed/cisplatin, respectively (HR 0.88; P=0.39) Overall survival (secondary endpoint) LUX-Lung 3 preplanned subgroup analysis Estimated OS probability Time of overall survival (months) months >12 months increase median OS 33.3 months >12 months increase median OS 46% reduction in relative risk of death

LUX-LUNG 3 Patient-reported outcomes

8 Afatinib significantly improved dyspnoea and some pain symptoms compared with pemetrexed/cisplatin * Improvement=a linear transformation was applied to standardise the raw score to a range from 0 to 100. A 10-point change is accepted as the threshold for being clinically meaningful 2 1.Yang JC et al. J Clin Oncol. 2013;31(27): Osoba D et al. J Clin Oncol. 1998;16(1): ) P=0.244 P=0.010 P<0.001 P=0.051 P=0.018 P=0.010 P=0.170 Patients with improvement in symptoms (EORTC scores improved by ≥10 points) 1 * >97% questionnaire completion >97% questionnaire completion

9 Afatinib delayed time to worsening of clinically relevant symptoms vs pemetrexed/cisplatin TTD=time to deterioration, the time from randomisation to first appearance of a score ≥10 points lower than the baseline score. EORTC=European Organisation for Research and Treatment of Cancer. 1.Yang JC et al. J Clin Oncol. 2013;31(27): Wu YL et al. Annals of Oncology (2014) 25 (suppl_4): iv426-iv /annonc/mdu349. Cough Dyspnoea Pain Median TTD (months) P=0.006 P=0.013 P= months 4.2 months 27.0 months Afatinib (n=230) Pem/cis (n=115) Median TTD of symptoms (EORTC QoL QLQ-C30 and QLQ LC-13) 1,2 >97% questionnaire completion >97% questionnaire completion

10 Afatinib significantly improved quality of life (QoL) vs pemetrexed/cisplatin Yang JC et al. J Clin Oncol. 2013;31(27): EORTC QLQ-C30 questionnaire scores Favours afatinib Favours pem/cis Significant difference favouring afatinib Differences in mean scores (95% confidence intervals) Global health status/QoL Physical functioning Role functioning Cognitive functioning Emotional functioning Social functioning >97% questionnaire completion >97% questionnaire completion

LUX-LUNG 3 Adverse events 11

12 The most common AEs with afatinib were diarrhoea, stomatitis, rash, acne, and paronychia ‒The most common adverse events with afatinib were generally manageable through supportive care Treatment-related discontinuation due to any AE was low (8% vs 12% for pemetrexed/cisplatin) ‒Discontinuation due to diarrhoea and rash/acne with afatinib was 1.3% and 0%, respectively Manageable adverse event profile in LUX-Lung 3 AE=adverse event. Sequist LV et al. J Clin Oncol. 2013;31(27):

13 Manageable adverse event profile in LUX-Lung 3 Sequist LV et al. J Clin Oncol. 2013;31(27): Events are included if reported in more than 10% of patients in either of the treatment groups and if there was at least 10% difference between the groups. Events are listed according to the incidence in the afatinib group. † Group term. ‡ Numbers are based on the AEs reported by the investigator and not derived from the laboratory data. Afatinib (n=229)Pem/cis (n=111) All grades (%)≥ grade 3 (%)All grades (%)≥ grade 3 (%) Diarrhoea218 (95.2)33 (14.4)17 (15.3)0 (0.0) Rash/acne † 204 (89.1)37 (16.2)7 (6.3)0 (0.0) Stomatitis/mucositis † 165 (72.1)20 (8.7)17(15.3)1 (0.9) Paronychia130 (56.8)26 (11.4)0 (0.0) Dry skin67 (29.3)1 (0.4)2 (1.8)0 (0.0) Decreased appetite47 (20.5)7 (3.1)59 (53.2)3 (2.7) Pruritis43 (18.8)1 (0.4)1 (0.9)0 (0.0) Nausea41 (17.9)2 (0.9)73 (65.8)4 (3.6) Fatigue † 40(17.5)3 (1.3)52 (46.8)14 (12.6) Vomiting39 (17.0)7 (3.1)47 (42.3)3 (2.7) Epistaxis30 (13.1)0 (0.0)1 (0.9) Cheilitis28 (12.2)0 (0.0)1 (0.9)0 (0.0) Anaemia ‡ 7 (3.1)1 (0.4)31 (27.9)7 (6.3) Constipation6 (2.6)0 (0.0)21 (18.9)0 (0.0) Leukopenia ‡ 4 (1.7)1 (0.4)21 (18.9)9 (8.1) Neutropenia ‡ 2 (0.9)1 (0.4)35 (31.5)20 (18.0)