IDEAL 1 and IDEAL 2

BR.21 Study Design R Stratified by: Centre Erlotinib* 150mg/day PS, 0/1 vs 2/3 Response to prior Rx (CR/PR:SD:PD) Prior regimens, (1 vs 2) Prior platinum, (Yes vs no) Erlotinib* 150mg/day R *2:1 Randomization Placebo “150 mg” daily BR 21 Shepherd et al. N Engl J Med. 2005;353:123-132. 2

BR.21 Progression-Free Survival ___ Erlotinib, _____ Placebo 2.2 mos 1.8 mos *HR 0.61, p <0.0001 *Adjusted for stratification factors (except centre) AND EGFR status BR 21 Months Shepherd et al. N Engl J Med. 2005;353:123-132.

Survival time (months) BR.21: Overall Survival 1.00 0.75 0.50 0.25 HR=0.70 (95% CI, 0.58-0.85); P < 0.001* *HR and P-value adjusted for stratification factors at randomization plus HER1/EGFR status. Survival distribution function 31% 42.5% improvement in median survival Pre-specified analyses in the statistical analysis plan for study BR.21 included stratifications on the basis of performance status, prior therapy (including platinum therapy), responsiveness to prior therapy, and HER1/EGFR status. Treatment of NSCLC patients with erlotinib resulted in a statistically significant improvement in the primary endpoint of overall survival versus placebo. In a univariate analysis of all patients, the hazard ratio was 0.72 (ie, patients treated with erlotinib had a 28% better chance of survival compared with placebo) Patients treated with erlotinib (median survival=6.7 months) survived 30% longer than placebo-treated patients (median survival=4.7 months). One-year survival rates were increased 48% by treatment with erlotinib. Erlotinib is the only HER1/EGFR inhibitor proven to prolong the survival of patients with advanced, refractory NSCLC. Erlotinib Placebo 21% 0 5 10 15 20 25 30 Survival time (months) Shepherd et al. N Engl J Med. 2005;353:123-132. 4 4

IPASS Study Design R Primary endpoint: PFS Gefitinib 250mg/day Chemonaïve advanced NSCLC Adenocarcinoma Non-smoker or light smoker N = 1217 R Paclitaxel (200 mg/m2, IV, d1) plus carboplatin (AUC=5 or 6 mg/min) repeated every 3 weeks up to 6 cycles Primary endpoint: PFS Secondary endpoints: ORR, OS, QoL and safety Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. Mok TS, et al. N Engl J Med. 2009 Sep 3;361(10):947-57. 5

IPASS: PFS and OS by Known EGFR Mutation Status 1.0 1.0 Gefitinib EGFR M+ Gefitinib EGFR M- C / P EGFR M+ C / P EGFR M- 4 8 16 24 12 20 0.8 0.8 Mutation + 0.6 0.6 Probability of survival 0.4 0.4 Probability of progression-free survival 0.2 0.2 Mutation - 0.0 0.0 4 8 12 16 20 24 28 32 36 IPASS 40 44 48 Time from randomisation (months) Time from randomisation (months) 52 Patients at risk excludes censored patients and those who have experienced an event Yang CH et al. ESMO 2010 6 6 6

INTEREST Study Design Endpoints Patients IRESSA 250 mg/day Age ≥18 years Life expectancy ≥8 weeks Progressive or recurrent disease following CT Considered candidates for further CT with docetaxel 1 or 2 CT regimens (≥1 platinum) PS 0-2 Primary Overall survival (co-primary analysesa of non-inferiority in all patients and superiority in patients with high EGFR gene copy number) Secondary Progression-free survival Objective response rate Quality of life Disease-related symptoms Safety and tolerability Exploratory Biomarkers IRESSA 250 mg/day 1:1 randomization Docetaxel 74 mg.m2 every 3 weeks INTEREST was an international, multicenter, randomized, open-label, parallel-group, Phase III study of IRESSA (gefitinib) versus docetaxel in patients with locally advanced or metastatic recurrent NSCLC who were pre-treated with platinum-based chemotherapy. Eligible patients were at least 18 years of age with NSCLC that had progressed or recurred following one or two prior therapies (at least one platinum based) and with a performance status of 0 to 2 and a life expectancy of >8 weeks. Patients were randomized to receive either IRESSA (250 mg/day orally) or docetaxel (1-hour 75 mg/m2 infusion every 3 weeks). The primary endpoint was overall survival using co-primary analyses of non-inferiority in all patients and superiority in patients with high epidermal growth factor receptor (EGFR) gene copy number. Secondary endpoints compared progression-free survival, objective response rate, quality of life, disease-related symptoms and safety and tolerability for IRESSA and docetaxel. Exploratory endpoints included the efficacy outcomes in biomarker subgroups defined by EGFR expression by immunohistochemistry (IHC), EGFR mutation and K-RAS mutation status. aModified Hochberg procedure applied to control for multiple testing CT: chemotherapy; PS: performance status Kim ES, et al. Lancet. 2008 Nov 22;372(9652):1809-18. 7 7

INTEREST: Gefitinib vs. Docetaxel in NSCLC After Chemotherapy Gefitinib demonstrated non-inferior survival compared with docetaxel OS in overall study population OS in patients with high EGFR gene copy number 1.0 0.8 HR (96% CI) = 1.020 (0.905, 1.150) HR (95% CI) = 1.09 (0.78, 1.51) P = 0.6199 0.6 Probability of survival Gefitinib Docetaxel 0.4 0.2 Pre-treated NSCLC INTEREST STUDY (D791GC00001) INTEREST was a Phase III, randomized, open-label, parallel-group, international, multicentre trial comparing IRESSA to docetaxel in 1466 patients with locally advanced or metastatic NSCLC who had previously received platinum-based chemotherapy and were eligible for further chemotherapy. Pre-planned exploratory subgroup analysis of 44 EGFR mutation positive patients provides supportive evidence for the approved indication. For patients with EGFR mutations, IRESSA was superior to docetaxel in terms of PFS (HR 0.16, 95% CI 0.05 to 0.49, p=0.0012) and ORR (42.1% vs 21.1%, p=0.00361). Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. 0.0 20 36 40 20 40 Months Months Kim ES, et al. Lancet. 2008 Nov 22;372(9652):1809-18. 8

SATURN Study Design R Erlotinib 150mg/day Placebo Run-in Period: Patients with advanced NSCLC Treatment with four cycles of platinum-doublet chemo N = 1949 Erlotinib 150mg/day Eligibility: No progressive disease N = 889 R Placebo Primary endpoint: PFS in all patients; PFS in patients with EGFR IHC- positive tumours Secondary endpoints: OS in ITT and EGFR-positive tumours, PFS in EGFR-negative tumours, time to progression, tumour response, QoL Cappuzzo F, et al. Lancet Oncol. 2010 Jun;11(6):521-9.

SATURN: Erlotinib vs. Placebo in NSCLC After Chemotherapy PFS OS 1.0 0.8 0.6 0.4 0.2 1.0 0.8 0.6 0.4 0.2 Erlotinib (n=437) Placebo (n=447) Erlotinib (n=438) Placebo (n=451) HR=0.71 (0.62–0.82) Log-rank p<0.0001 HR=0.81 (0.70–0.95) Log-rank p=0.0088 Probability Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczésna A, Juhász E, Esteban E, Molinier O, Brugger W, Melezínek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010 Jun;11(6):521-9. 0 8 16 24 32 40 48 56 64 72 80 88 96 0 8 16 24 32 40 48 56 64 72 80 88 96 Time (weeks) Time (weeks) Cappuzzo F, et al. Lancet Oncol. 2010 Jun;11(6):521-9. 10

SATURN: EGFR Activating Mutations PFS1 OS2 1.0 0.8 0.6 0.4 0.2 1.0 0.8 0.6 0.4 0.2 HR=0.10 (0.04–0.25) Log-rank p<0.0001 HR=0.83 (0.34–2.02) Log-rank p=0.6810 Probability Erlotinib (n=22) Placebo (n=27) Erlotinib (n=22) Placebo (n=27) Significantly improved PFS with erlotinib vs. placebo in patients with EGFR MUT +ve disease OS data not yet mature (N.B. 67% of patients with EGFR MUT +ve disease in placebo arm received a second-line EGFR TKI) Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczésna A, Juhász E, Esteban E, Molinier O, Brugger W, Melezínek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010 Jun;11(6):521-9. Brugger, et al. J Thorac Oncol 2009;4 (Suppl. 1):S348–9 (Abs. B9.1) 0 8 16 24 32 40 48 56 64 72 80 88 96 0 3 6 9 12 15 18 21 24 27 30 33 36 Time (weeks) Time (months) 1. Cappuzzo F, et al. Lancet Oncol. 2010 Jun;11(6):521-9. 2. Brugger, et al. J Thorac Oncol 2009;4 (Suppl. 1):S348–9 (Abs. B9.1) 11 11 11

PFS: Overall Population Dacomitinib versus Erlotinib Phase ll Overall population 100 90 80 70 60 50 40 30 20 10 PF299804 (n=94) Median: 12.4 weeks (95% CI: 8.3–16.1) Erlotinib (n=94) Median: 8.3 weeks (95% CI: 8.0–11.4) Progression-free survival probability (%) Dacomitinib Phase 2 Unstratified analysis: Hazard ratio = 0.681 (95% CI: 0.490–0.945) Log-rank P-value = 0.019 0 5 10 15 20 25 30 35 40 45 50 55 60 Time (weeks) CI = confidence interval Post-baseline tumor assessments were initiated at week 8 and conducted every 4 weeks thereafter. Boyer et al ASCO 2010. Abstract LBA7523.

AFATINIB: PRECLINICAL ACTIVITY Drug IC50 (nM) WT L858R Exon 19 Del L858R/T790M Afatinib1 60 0.7 0.5 50 Erlotinib2 110 40 3.8 >4,000 Gefitinib3, 4 157 10-63 PF-8045 29-63 7 2-4 119 Afatinib 1. Oncogene 2008;27:4702-4711. 2.Cancer Res 2006;66:8163-71. 3. Science 2004;304:1497. 4. JNCI 2005;97:1185-94. 5. Cancer Res 2007; 67:11924-32.

PFS by independent review Afatinib Statistically significant across almost all subgroups