1. Clinicopathologic Features of EML4-ALK Mutant Lung Cancer Shaw AT et al. ASCO 2009; Abstract 11021. (Poster)

2. Source: Shaw AT et al. ASCO 2009; Abstract 11021. Introduction EML4-ALK (anaplastic lymphoma kinase) is a novel fusion oncogene in NSCLC –The fusion results from a small inversion within chromosome 2p, leading to expression of a constitutively activated, chimeric tyrosine kinase Multiple EML4-ALK variants exist but one is specific to NSCLC –Mostly in adenocarcinoma –Non-overlapping with EGFR mutated The clinical and pathologic features of patients with EML4-ALK mutant NSCLC has not been definitively established and their clinical outcome is unknown Current study objectives: –Define the clinicopathologic features, treatment response and survival of patients with EML4-ALK mutated NSCLC

3. Fusion of EML4 with ALK in NSCLC Source: Shaw AT et al. ASCO 2009; Abstract 11021. The EML4-ALK fusion oncogene represents one of the newest molecular targets in NSCLC. First described in 2007, the fusion results from a small inversion within chromosome 2p, leading to expression of a chimeric tyrosine kinase in which the N-terminal half of EML4 is fused to the intracellular kinase domain of ALK

4. Patients and Methods Source: Shaw AT et al. ASCO 2009; Abstract 11021. Patients Thoracic Oncology Clinic Biopsy-proven NSCLC Selection Criteria (≥ 2 of the following) Never or light smoking history Adenocarcinoma histology Female gender Asian ethnicity Genetic Mutation Testing EGFR EML4-ALK (by FISH, confirmed by IHC) N = 141 screened

5. Demographic Features of Patients by EML4-ALK and EGFR Mutation Status Source: Shaw AT et al. ASCO 2009; Abstract 11021. Characteristic ALK+ (n = 19) EGFR+ (n = 31) Wild Type/Wild Type † (n = 91) Mutant*13%*22%*65%* Age (median)52 yrs66 yrs64 yrs Gender Male Female 58% 42% 26% 74% 32% 68% Smoking history Never smoker Light smoker Smoker 74% 26% 0% 68% 19% 13% 26% 16% 57% *No ALK mutant tumors were EFGR mutant — non-overlapping † ALK Wild Type/EGFR Wild Type The majority of tumors were adenocarcinomas, with ALK but not EGFR mutant tumors strongly associated with signet ring cell subtype

6. Clinical Outcome of Patients by EML4-ALK and EGFR Mutation Status Source: Shaw AT et al. ASCO 2009; Abstract 11021. ALK+ (n = 19) EGFR+ (n = 31) WT/WT † (n = 91) Chemotherapy (platinum-doublet) Response rate Time to progression 25% 9 mos 50% 10 mos 35% 8 mos EGFR TKI Response rate Time to progression 0% 5 mos 70% 16 mos 13% 6 mos Median survival20 mos32 mos16 mos † ALK Wild Type/EGFR Wild Type

7. EML4-ALK+ defines a new molecular subset of NSCLC, with distinct clinical and pathologic characteristics –13% of this select patient population –Non-overlapping with EGFR mutants –Mostly adenocarcinomas - signet-ring cell subtype –Younger age (Median 52 years old) –More likely to be male (58%) The frequency of EML4-ALK is high in light/never smokers without EGFR+ –Light/never smoking history (100%) These patients do not benefit from EGFR TKIs and should be treated with other standard agents or ALK targeted therapies –Resistant to EGFR TKIs (ORR = 0%) –Chemotherapy response rate and 1-year survival is similar to patients with wild-type tumors –Novel ALK and MET kinase inhibitors may offer promising treatment options for patients with ALK mutant NSCLC (See Kwak et al, ASCO 2009) Source: Shaw AT et al. ASCO 2009; Abstract 11021. Summary and Conclusions

8. Clinical Activity Observed in a Phase I Dose-Escalation Trial of an Oral MET and ALK Inhibitor, PF-02341066 Kwak EL et al. ASCO 2009; Abstract 3509. (Oral Presentation)

9. Tumor Response to PF-02341066 in 19 Pretreated Patients with NSCLC and ALK Fusion Mutations Source: Kwak EL et al. ASCO 2009; Abstract 3509. PF-02341066, a selective ATP competitive oral inhibitor of MET and ALK kinases Overall response rate: 53% Disease control rate at 8 weeks: 79%