1. CR-1 Actions Ongoing Clinical Development Judith S. Ochs, MD

2. CR-2 Immediate Actions Agreed With FDA ●Communicate rapidly and extensively Enable informed physician decision making Reduce the numbers of patients receiving IRESSA ® for the first time Provide FDA with prescription data q 2 wk ●Maintain IRESSA ® availability ●Rapidly provide full data to FDA for review ●Communicate rapidly and extensively Enable informed physician decision making Reduce the numbers of patients receiving IRESSA ® for the first time Provide FDA with prescription data q 2 wk ●Maintain IRESSA ® availability ●Rapidly provide full data to FDA for review

3. CR-3 Communications—December 17, 2004 AstraZeneca actions ●Press release ●~ 141,000 Dear Doctor Letters (DDL) ●Sales force distribution of DDL ●DDL posted to Web sites ●Patient advocate groups notified ●Clinical trial investigators, NCI notified ●Promotional activity suspended External actions ●ASCO e-mail from FDA ●Information posted on FDA Web site AstraZeneca actions ●Press release ●~ 141,000 Dear Doctor Letters (DDL) ●Sales force distribution of DDL ●DDL posted to Web sites ●Patient advocate groups notified ●Clinical trial investigators, NCI notified ●Promotional activity suspended External actions ●ASCO e-mail from FDA ●Information posted on FDA Web site

4. CR-4 Further Communications ●Presentation at ODAC ●Communications to healthcare professionals Journal placement of DDL AACR, WCLC abstracts Manuscript in preparation ●Presentation at ODAC ●Communications to healthcare professionals Journal placement of DDL AACR, WCLC abstracts Manuscript in preparation

5. CR-5

6. CR-6 Feb/March Journal Placement ●American Journal Oncology Reviews ●Clinical Lung Cancer ●Clinical Advances in Hematology & Oncology ●Hematology/Oncology Today ●JAMA Oncology Subscriber ●Journal of Clinical Oncology ●New England Journal Oncology Subscriber ●Oncology ●Oncology Times ●The Oncologist ●American Journal Oncology Reviews ●Clinical Lung Cancer ●Clinical Advances in Hematology & Oncology ●Hematology/Oncology Today ●JAMA Oncology Subscriber ●Journal of Clinical Oncology ●New England Journal Oncology Subscriber ●Oncology ●Oncology Times ●The Oncologist

7. CR-7 Impact on IRESSA ® Usage ●Total and new prescriptions for IRESSA ® have significantly decreased Total prescriptions are 49% lower New prescriptions are 58% lower ●Market research 78% clinical oncologists aware of DDL content 86% modifying treatment practice ●Total and new prescriptions for IRESSA ® have significantly decreased Total prescriptions are 49% lower New prescriptions are 58% lower ●Market research 78% clinical oncologists aware of DDL content 86% modifying treatment practice

8. CR-8 Clinical Implications and Next Steps

9. CR-9 Pertinent Questions to Ask ●Why did this result occur? How does this result compare to other data on IRESSA ® in NSCLC? The play of chance? Dose selection strategy? Trial population and geography? ●What biologic data may be available to better understand the outcomes? ●What other relevant clinical data are expected? ●Why did this result occur? How does this result compare to other data on IRESSA ® in NSCLC? The play of chance? Dose selection strategy? Trial population and geography? ●What biologic data may be available to better understand the outcomes? ●What other relevant clinical data are expected?

10. CR-10 Adenocarcinoma All patients Female PS 0,1 1 prior chemo Refractory Never smoked Non-adenocarcinoma Ever smoked Intolerant 2 prior chemos PS 2,3 Male Hazard ratio and 95% CI Favors IRESSA ® Favors placebo 11.4 7.7 14.0 8.3 7.4 7.8 17.2 4.6 5.2 7.2 8.0 6.6 4.9 Response rate, % Trial 709Phase II Survival Consistency of Outcome Between Trial 709 and Phase II Data (1) 13.8 10.2 20.7 10.4 26.8 5.3 7.1 10.5 9.8 4.4 NA 9.3

11. CR-11 Prior docetaxel All patients Asian ethnicity Time since Dx: >12 mo Time since Dx: <6 mo <65 yr No prior docetaxel ≥65 yr Time since Dx: 6-12 mo Non-Asian ethnicity Hazard ratio and 95% CI Favors IRESSA ® Favors placebo Prior chemo response: PD/NE Prior chemo response: CR/PR Prior chemo response: SD 10.3 7.7 12.0 9.3 6.8 7.1 6.7 8.7 6.9 6.5 7.0 8.9 8.0 Survival Consistency of Outcome Between Trial 709 and Phase II Data (2) 11.1 10.2 27.5 12.4 10.0 10.7 6.0 10.4 NA 5.3 NA Response rate, % Trial 709Phase II 8.0 NA

12. CR-12 The Play of Chance? ●Is the overall outcome in Trial 709 inconsistent with that seen in erlotinib study (BR21)? BR21 Trial 709 Survival Response rate, % Favors active agentFavors placebo 9 8

13. CR-13 Dose Selection Strategy ●Doses up to 1000 mg explored in extensive Phase I program ●250 mg and 500 mg compared in randomized Phase II trials in 416 patients No difference in survival Increased toxicity at 500 mg ●No data to suggest doses above 500 mg would achieve better outcomes but cannot be ruled out completely ●Doses up to 1000 mg explored in extensive Phase I program ●250 mg and 500 mg compared in randomized Phase II trials in 416 patients No difference in survival Increased toxicity at 500 mg ●No data to suggest doses above 500 mg would achieve better outcomes but cannot be ruled out completely

14. CR-14 Methodologic: Areas to Explore ●Highly refractory population? ●Cultural or environmental differences between regions? Smoking exposure ●Highly refractory population? ●Cultural or environmental differences between regions? Smoking exposure

15. CR-15 What Does This Mean? ●IRESSA ® is an active and well-tolerated agent ●Data consistent with Phase II and large clinical experience ●Variability in outcome, with significant survival increase in Never smokers Asian patients ●Biomarker studies from Trial 709 may help in further interpretation of results ●IRESSA ® is an active and well-tolerated agent ●Data consistent with Phase II and large clinical experience ●Variability in outcome, with significant survival increase in Never smokers Asian patients ●Biomarker studies from Trial 709 may help in further interpretation of results

16. CR-16 Biomarkers of Interest in NSCLC ●EGFR expression Exploratory analyses from Phase II IDEAL studies Relationship with survival shown for erlotinib ●EGFR activating mutations Described in dramatic responders to IRESSA ® ●Other exploratory biomarkers EGFR gene copy number HER-family dimerization patterns ●EGFR expression Exploratory analyses from Phase II IDEAL studies Relationship with survival shown for erlotinib ●EGFR activating mutations Described in dramatic responders to IRESSA ® ●Other exploratory biomarkers EGFR gene copy number HER-family dimerization patterns

17. Relationship Between EGFR Expression and Survival for Erlotinib BR21 A positive EGFR expression status was defined as having at least 10% of cells staining for EGFR in contrast to the 1% cut-off specified in the DAKO EGFR pharmDx™ kit instructions. The use of the pharmDx kit has not been validated for use in Non-Small Cell Lung Cancer. TARCEVA prolonged survival in the EGFR positive subgroup (N = 127; HR = 0.65; 95% CI = 0.43 - 0.97) (figure 3) and the subgroup whose EGFR status was unmeasured (N = 493; HR = 0.76; 95% CI = 0.61 - 0.93) (figure 5), but did not appear to have an effect on survival in the EGFR negative subgroup (N = 111; HR = 1.01; 95% CI = 0.65 - 1.57) (figure 4). However, the confidence intervals for the EGFR positive, negative and unmeasured subgroups are wide and overlap, so that a survival benefit due to TARCEVA in the EGFR negative subgroup cannot be excluded. CR-17

18. CR-18 Mutation of the EGFR Tyrosine Kinase in Human Non-Small Cell Lung Carcinoma ●Mutation appears almost exclusively in NSCLC ●Mutation is activating, in ATP-binding site ●Mutation more frequent in Females Adenocarcinomas Never smokers ●Frequency of mutation approx. 12% in Caucasian, 26% in Asian population ●Incomplete association of mutation with response in IDEAL studies (6/14 PR in mutation+) Paez J, Janne, PA, Lee JC, et al. Science. April 29 2004; Lynch TJ, Bell DW, Sordella et al. N Engl J Med. April 30 2004.

19. CR-19 Biologic Correlations Summary of Currently Available Data ●EGFR expression appears to be associated with increased survival in BR21 ●EGFR mutations appear to explain some, but not all, of the responses to IRESSA ® ●Outcomes in trial 709 comparing IRESSA ® to placebo will be explored in terms of EGFR expression, activating mutation and other biomarkers Data available in June 2005 Results may provide further insight into clinical outcomes ●Prospective studies needed ●EGFR expression appears to be associated with increased survival in BR21 ●EGFR mutations appear to explain some, but not all, of the responses to IRESSA ® ●Outcomes in trial 709 comparing IRESSA ® to placebo will be explored in terms of EGFR expression, activating mutation and other biomarkers Data available in June 2005 Results may provide further insight into clinical outcomes ●Prospective studies needed

20. CR-20 Prospective Studies to Investigate Predictive Markers and Outcome in NSCLC ●IRESSA ® vs. doublet chemotherapy Mandatory tissue collection to evaluate further utility of defined biomarkers ●Targeted study population Mutation+ Never smokers ●Specific studies in Asian population(s) ●IRESSA ® vs. doublet chemotherapy Mandatory tissue collection to evaluate further utility of defined biomarkers ●Targeted study population Mutation+ Never smokers ●Specific studies in Asian population(s)

21. CR-21 Further Studies in Advanced NSCLC ●Trial 721—IRESSA ® vs. docetaxel Post-approval commitment (n = 1440) Interim analysis: ~ May-June with 380 deaths ●IRESSA ® vs. docetaxel Japan post-approval commitment (n = 484) ●Phase II Trial 503: IRESSA ® vs. docetaxel Supportive of Trial 721 and dose ●Trial 721—IRESSA ® vs. docetaxel Post-approval commitment (n = 1440) Interim analysis: ~ May-June with 380 deaths ●IRESSA ® vs. docetaxel Japan post-approval commitment (n = 484) ●Phase II Trial 503: IRESSA ® vs. docetaxel Supportive of Trial 721 and dose

22. CR-22 Trial 503—IRESSA ® 250 mg Daily vs. Docetaxel 75 mg/m 2 IRESSA ® Docetaxel Median (mo)7.57.1 HR = 0.96 (0.61, 1.52), P =.87 N = 141, 55% mortality Time, mo 02468101214 ——IRESSA ® ------Docetaxel Patients surviving (%) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0

23. CR-23 Clinical Summary ●Well-tolerated agents like IRESSA ® are an accepted addition to the therapeutic armamentarium ●Clinical and translational data are pointing the way to most appropriate use ●AstraZeneca remains committed to IRESSA ® and other biologically targeted agents ●Well-tolerated agents like IRESSA ® are an accepted addition to the therapeutic armamentarium ●Clinical and translational data are pointing the way to most appropriate use ●AstraZeneca remains committed to IRESSA ® and other biologically targeted agents