1 Sitemap Storyflow Title slideOverview slide13.6 months PFSSymptom controlQoL OS across 7 trials3 months OS > 12 month OS Summary slide

2 Sitemap Storyflow + sub pages Title slideOverview slide13.6 months PFSSymptom controlQoL OS across 7 trials3 months OS > 12 month OS Summary slide PFS comparison Subsequent therapyOS Forest Plot Del 19OS Forest Plot L858RPFS Forest Plot L858R

3 GIOTRIF ® (afatinib) as monotherapy is indicated for the treatment of Epidermal Growth Factor Receptor (EGFR) TKI- naïve adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation(s). * Secondary endpoint, primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (del19/L858R) vs chemotherapy (LUX-lung 3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). EGFR M+=epidermal growth factor receptor mutation positive; NSCLC=non-small cell lung cancer; OS=overall survival. 1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^). GIOTRIF ® - First targeted therapy to show significant first-line OS benefit in EGFR M+ NSCLC* 1

4 GIOTRIF ® – First approved irreversible ErbB Family Blocker 1 * vs pemetrexed/cisplatin in prespecified subgroup of patients with common mutations (del19/L858R); ** Secondary endpoint, primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (del19/L858R) vs chemotherapy (LUX-lung 3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). † vs pemetrexed/cisplatin. PFS=progression-free survival; QoL=quality of life. 1.Solca F et al. J Pharmacol Exp Ther. 2012;343(2): Sequist LV et al. J Clin Oncol. 2013;31(27): Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^). 4.Yang JC et al. J Clin Oncol. 2013;31(27): Clinically meaningful Symptom Improvement †4 Significant Overall Survival benefit ** 3 Significantly better QoL † months PFS (del19/L858R) * 2

5 GIOTRIF ® – First approved irreversible ErbB Family Blocker 1 Clinically meaningful Symptom Improvement vs. pemetrexed/cisplatin †4 Significant Overall Survival benefit vs. pemetrexed/cisplatin or gemcitabine/cisplatin ** 3 Significantly better QoL vs. pemetrexed/cisplatin † months PFS vs. pemetrexed/cisplatin (del19/L858R) * 2 * vs pemetrexed/cisplatin in prespecified subgroup of patients with common mutations (del19/L858R); ** Secondary endpoint, primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (del19/L858R) vs chemotherapy (LUX-lung 3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). † vs pemetrexed/cisplatin. PFS=progression-free survival; QoL=quality of life. 1.Solca F et al. J Pharmacol Exp Ther. 2012;343(2): Sequist LV et al. J Clin Oncol. 2013;31(27): Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^). 4.Yang JC et al. J Clin Oncol. 2013;31(27):

6 Del9/L858R mutations LUX-Lung 3 prespecified subgroup analysis GIOTRIF ® – Superior first-line PFS vs pemetrexed/cispatin in common mutations (del19/L858R) 1 PFS=progression-free survival. 1.Sequist LV et al. J Clin Oncol. 2013;31(27): PFS rate (%) Time (months) Hazard ratio 0.47 (95% CI, ) P<0.001 GIOTRIF ® (n=204) Pemetrexed/cisplatin (n=104) 13.6 months ~90% of patients in LUX-Lung 3 had common mutations (del19/L858R) 6.9 months

7 GIOTRIF ® – Longer PFS than reversible TKIs when indirectly compared The data presented above come from separate studies with different designs and therefore results cannot be directly compared. * Common EGFR mutations (Del19/L858R); † Prespecified subgroup analysis (89% of patients); ‡ Common and uncommon muatations; PFS=progression-free survival; TKI=tyrosine kinase inhibitor. 1.Sequist LV et al. J Clin Oncol. 2013;31(27): Rosell R et al. Lancet Oncol. 2012;13(3): Mok TS et al. New Engl J Med 2009;361: Median PFS (months) LUX-Lung 3 1 EURTAC 2 IPASS 3 Cisplatin + Pemetrexed ErlotinibCisplatin/ carboplatin + gemcitabine/ docetaxel GIOTRIF ® GefitinibCarboplatin + Paclitaxel 13.6* † 6.9* † 5.2* 9.5 ‡ 6.3 ‡ 9.7* PFS in first-line phase III registration trials in NSCLC

8 GIOTRIF ® – Delayed time to deterioration of clinically relevant symptoms 1 TTD=time to deterioration. EORTC=European Organisation for Research and Treatment of Cancer. 1.Yang JC et al. J Clin Oncol. 2013;31(27): LUX-Lung 3: TTD of symptoms (EORTC QoL QLQ-C30 and QLQ LC-13) Cough Dyspnoea Pain Median TTD (months) p=0.007 p=0.015 p= months 4.2 months Median not reached GIOTRIF ® (n=230) Cis/Pem (n=115) >97% questionnaire completion

9 GIOTRIF ® – Significantly improved QoL vs pemetrexed/cisplatin 1 Qo=quality of life. EORTC=European Organisation for Research and Treatment of Cancer. 1. Yang JC et al. J Clin Oncol. 2013;31(27): Global health status/QoL Physical functioning Role functioning Cognitive functioning Emotional functioning Social functioning Favours GIOTRIF ® Favours pem/cisSignificant difference favouring GIOTRIF ® Differences in mean scores (95% confidence intervals) >97% questionnaire completion LUX-Lung 3: EORTC QLQ-C30 questionnaire scores longitudinal analysis

10 No first-line OS benefit demonstrated with reversible EGFR TKIs N/A=not applicable; NS=not significant; OS=overall survival; TKI=tyrosine kinase inhibitor. 1.TARCEVA ® (erlotinib) prescribing information, Fukuoka et al. J Clin Oncol. 2011;29: Wu et al. J Thorac Oncol. 2013;8:suppl 2 (P ) 4.Zhou et al. J Clin Oncol 30, 2012 (suppl; abstr 7520). 5.Inoue et al. Ann Oncol. 2013;24: Yoshioka H, et al. J Clin Oncol 32:5s, 2014 (suppl; abstr 8117). 7.Han et al. J Clin Oncol. 2012;30: Trial Reversible EGFR TKI Registration trial Hazard ratio Overall survival p value EURTAC 1 ErlotinibYes0.93NS IPASS 2 GefitinibYes1.0NS ENSURE 3 ErlotinibNoN/ANS OPTIMAL 4 ErlotinibNo1.04NS NEJ002 5 GefitinibNo0.89NS WJTOG GefitinibNo1.25NS FIRST-SIGNAL 7 GefitinibNo1.04NS First-line phase III trials with reversible EGFR TKIs

11 Del19/L858R mutations Post-hoc combined analysis (LUX-Lung 3 & 6) GIOTRIF ® – Significantly increased first-line OS vs chemotherapy* 1 * Secondary endpoint, primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (Del19/L858R) vs chemotherapy (LUX-lung 3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). ITT=intent to treat; OS=overall survival. 1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^). Estimated OS probability Time of overall survival (months) 27.3 months Hazard ratio 0.81 (95% CI, ) P= GIOTRIF ® (n=419) Chemotherapy (n=212) 24.3 months months median OS The proportion of patients who received subsequent therapies was balanced in both arms OS in ITT population (N=345) was and months for GIOTRIF ® vs pemetrexed/cisplatin, respectively (HR 0.88, 95% CI, ; P=0.3850)

12 GIOTRIF ® – balanced subsequent therapy validates OS outcome 1 TKI = tyrosine kinase inhibitor. 1. Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^). Subsequent therapy in LUX-Lung 3 and 6 The proportion of patients who received subsequent therapies was balanced in both arms Trial (% patients) with subsequent therapy GIOTRIF ® Pem/cis or gem/cis LUX-Lung 371% chemo75% EGFR TKI LUX-Lung 659% chemo56% EGFR TKI

13 Del19 mutations LUX-Lung 3 overall survival GIOTRIF ® – Pronounced OS benefit in del19 (exon 19) patients 1 Estimated OS probability Time of overall survival (months) months Hazard ratio 0.54 (95% CI, ) P= GIOTRIF ® (n=112) Pemetrexed/cisplatin (n=57) 21.1 months OS=overall survival. 1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^). Over 1 year extended survival with GIOTRIF ® vs pem/cis in del19 (exon 19) patients (P=0.0015) Over 1 year extended survival also demonstrated in LUX-Lung 6 >12 months increase median OS

14 GIOTRIF ® – First targeted therapy to offer del19 (exon 19) patients a significant OS benefit 1-6 OS=overall survival; HR=hazard ratio. 1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^). 2.Mok et al. N Engl J Med. 2009;361: Yang et al. Eur J of Cancer (suppl1;S633). 4.Rosell et al. Lancet Oncol. 2012;13: TARCEVA ® (erlotinib) prescribing information ~50% of patients in LUX-Lung 3 and 6 had del19 mutations Favours targeted therapyFavours chemotherapy 1/ GIOTRIF ® EURTAC 4,5 Erlotinib0.94 (0.57 – 1.54) IPASS 2,3 Gefitinib0.79 (0.54 – 1.15) LUX-Lung (0.44 – 0.94) LUX-Lung (0.36 – 0.79) HR (95% CI) OS in registration trials in del19 (exon 19) patients

15 No OS benefit yet demonstrated by targeted therapies in L858R (exon 21) patients 1-6 OS=overall survival; HR=hazard ratio. 1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^). 2.Mok et al. N Engl J Med. 2009;361: Fukuoka et al. J Clin Oncol. 2011;29: Yang et al. Eur J of Cancer (suppl1;S633). 5.Rosell et al. Lancet Oncol. 2012;13: TARCEVA ® (erlotinib) prescribing information ~40% of patients in LUX-Lung 3 and 6 had L858R mutations Favours targeted therapyFavours chemotherapy GIOTRIF ® EURTAC 5,6 Erlotinib IPASS 2-4 Gefitinib LUX-Lung 6 1 LUX-Lung 3 1 HR (95% CI) OS in registration trials in L858R (exon 21) patients 1.30 (0.80 – 2.11) 1.22 (0.81 – 1.83) 1.44 (0.90 – 2.30) 0.99 (0.56 – 1.76) 1/

GIOTRIF ® – Superior PFS vs chemotherapy in L858R (exon 21) patients OS=overall survival, HR=hazard ratio. 1.Sequist LV et al. J Clin Oncol. 2013;31(27): Wu YL et al. Lancet Oncol. 2014;15(2): Mok et al. N Engl J Med. 2009;361: Fukuoka et al. J Clin Oncol. 2011;29: Rosell et al. Lancet Oncol. 2012;13: Favours targeted therapyFavours chemotherapy GIOTRIF ® EURTAC 5 Investigator review Erlotinib IPASS 3,4 Investigator review Gefitinib LUX-Lung 6 2 Independent review LUX-Lung 3 1 Investigator review HR (95% CI) PFS in registration trials in L858R (exon 21) patients 0.60 (0.39 – 0.93) 0.32 ( 0.19 – 0.52) 0.55 (0.35 – 0.87) 0.55 ( 0.29 – 1.02) 1/

17 Clinically meaningful Symptom Improvement †4 Significant Overall Survival benefit ** 3 Significantly better QoL † months PFS (del19/L858R) * 2 GIOTRIF ® – Longer, better life for your patients* 1,2 * vs pemetrexed/cisplatin in prespecified subgroup of patients with common mutations (del19/L858R); ** Secondary endpoint, primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (del19/L858R) vs chemotherapy (LUX-lung 3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). † vs pemetrexed/cisplatin. PFS=progression-free survival; QoL=quality of life. 1.Solca F et al. J Pharmacol Exp Ther. 2012;343(2): Sequist LV et al. J Clin Oncol. 2013;31(27): Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^). 4.Yang JC et al. J Clin Oncol. 2013;31(27):

18 Back-up

19 Majority of patients in LUX-Lung 3 had del19 (exon 19) mutations Del19 (exon 19) and L858R (exon 21) mutations represent approximately 90% of EGFR mutations in NSCLC — Del19 mutations consist of in-frame deletions of amino acids — L858R mutations are exon 21 point mutations 1. Sequist LV et al. J Clin Oncol. 2013;31(27):

20 All EGFR mutations LUX-Lung 3 PFS by independent review GIOTRIF ® - superior first-line PFS vs pemetrexed/cisplatin 1 PFS=progression-free survival. 1. Sequist LV et al. J Clin Oncol. 2013;31(27): PFS rate (%) months Hazard ratio 0.58 (95% CI, ) P<0.001 GIOTRIF ® (n=230) Pemetrexed/cisplatin (n=115) 6.9 months Time (months) At the time of primary analysis, a total of 45 (20%) patients treated with GIOTRIF® and 3 (3%) patients treated with chemotherapy were known to be alive and progression-free and are censored in the above graph. The primary PFS analysis was conducted after a total of 221 PFS events; it included 152 patients (66.1%) in the GIOTRIF ® arm

21 All EGFR mutations LUX-Lung 6 PFS by independent review GIOTRIF ® - superior first-line PFS vs gemcitabine/cisplatin 1 PFS=progression-free survival. 1.Wu YL et al. Lancet Oncol. 2014;15(2): PFS rate (%) months Hazard ratio 0.28 (95% CI, ) P< GIOTRIF ® (n=242) Pemetrexed/cisplatin (n=122) 5.6 months Time (months)

22 GIOTRIF ® – Delayed time to deterioration of clinically relevant symptoms 1 TTD=time to deterioration. EORTC=European Organisation for Research and Treatment of Cancer. 1. Yang JC et al. J Clin Oncol. 2013;31(27): GIOTRIF ® n=230 Pem/cis n=5 Median TTD (months) Not reached 8.0 Hazard ratio % CI, P=0.007 GIOTRIF ® n=230 Pem/cis n=115 Median TTD (months) Hazard ratio % CI, P=0.015 GIOTRIF ® n=230 Pem/cis n=115 Median TTD (months) Hazard ratio % CI, P=0.19 Cough: significantly delayed TTDDyspnoea: significantly delayed TTDPain: trend to longer TTD LUX-Lung 3: TTD of symptoms (EORTC QoL QLQ-C30 and QLQ LC-13)

23 Del19 mutations Prespecified LUX-Lung 3 analysis Prespecified LUX-Lung 3 analysis, del19: Over 2.5 years OS with 1 year improvement over pem/cis 1 Estimated OS probability Time of overall survival (months) months Hazard ratio 0.54 (95% CI, ) P= GIOTRIF ® (n=112) Pemetrexed/cisplatin (n=57) 21.1 months OS=overall survival. Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).

24 L858R mutations Prespecified LUX-Lung 3 analysis Prespecified LUX-Lung 3 analysis, L858R: Over 2 years OS 1 Estimated OS probability Time of overall survival (months) Hazard ratio 1.30* (95% CI, ) P= GIOTRIF ® (n=91) Pemetrexed/cisplatin (n=47) 40.3 months 27.6 *HR=1.02 (0.62, 1.69), when adjusted for baseline imbalances OS=overall survival. Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).

25 Del19 mutations Prespecified LUX-Lung 6 analysis Prespecified LUX-Lung 6 analysis, del19: Over 2.5 years OS with 1 year improvement over pem/cis 1 Estimated OS probability Time of overall survival (months) months Hazard ratio 0.64 (95% CI, ) P= GIOTRIF ® (n=124) Pemetrexed/cisplatin (n=62) 18.4 months OS=overall survival. 1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).

26 L858R mutations Prespecified LUX-Lung 6 analysis Prespecified LUX-Lung 6 analysis, L858R: Over 1.5 years OS 1 Estimated OS probability Time of overall survival (months) Hazard ratio 1.22 (95% CI, ) P= GIOTRIF ® (n=92) Pemetrexed/cisplatin (n=46) OS=overall survival. 1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^) months 19.6

27 Over 2.5 years OS with 1 year improvement over chemotherapy** GIOTRIF ® approved for use in these patients NCCN recommended (cat 1) Del19 (exon 19) GIOTRIF ® Approved for use in these patients NCCN recommended (cat 1) L858R (exon 21) Superior PFS* Significant improvements in symptoms and QoL* GIOTRIF ® continues to be a treatment option for L858R patients GIOTRIF ® should be the standard of care for del19 patients How do these results impact current practice? * vs chemotherapy (LUX-Lung 3 pemetrexed/cisplatin, LUX-Lung 6 gemcitabine/cisplatin) ** Secondary endpoint, primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (del19/L858R) vs chemotherapy (LUX-lung 3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). OS=overall survival; PFS=progression-free survival; QoL=quality of life; NCCN=National Comprehensive Cancer Network Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^). National Comprehensive Cancer Network Guidelines Version All EGFR mutations