1. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Randomized, open-label, phase 3 study of panitumumab (pmab) with FOLFIRI vs FOLFIRI alone as 2nd ‑ line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC): Efficacy by skin toxicity (ST) Timothy Price, 1 Alberto Sobrero, 2 Gregory Wilson, 3 Eric Van Cutsem, 4 Birute Aleknaviciene, 5 Alberto Zaniboni, 6 Jörg Thomas Hartmann, 7 Ying Tian, 8 Jennifer Gansert, 8 Marc Peeters 9 1 Queen Elizabeth Hospital, Woodville, Australia; 2 Ospedale San Martino, Genova, Italy; 3 Christie Hospital, Manchester, United Kingdom; 4 University Hospital Gasthuisberg, Leuven, Belgium; 5 Vilniaus Universiteto Onkologijos Institutas, Vilnius, Lithuania; 6 Casa di Cura Poliambulanza, Brescia, Italy; 7 Universitätsklinikum Kiel, Kiel, Germany; 8 Amgen Inc., Thousand Oaks, California, USA; 9 University Hospital Ghent, Ghent, Belgium

2. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Introduction Panitumumab, a fully human monoclonal antibody targeting the EGFR, is approved for use as monotherapy for chemorefractory mCRC 1,2 in patients with wild-type (WT) KRAS tumors 2Panitumumab, a fully human monoclonal antibody targeting the EGFR, is approved for use as monotherapy for chemorefractory mCRC 1,2 in patients with wild-type (WT) KRAS tumors 2 Study 20050181 is an open-label, randomized, global, phase 3 trial investigating the addition of panitumumab to FOLFIRI chemotherapy as 2 nd ‑ line treatment (tx) for patients with mCRC by KRAS mutational status Study 20050181 is an open-label, randomized, global, phase 3 trial investigating the addition of panitumumab to FOLFIRI chemotherapy as 2 nd ‑ line treatment (tx) for patients with mCRC by KRAS mutational status –Originally designed to compare the tx effect in the all randomized population, the study was amended to focus on hypothesis testing in the WT KRAS subset Primary findings were previously presented 3Primary findings were previously presented 3 Skin-related toxicities are the most common adverse events associated with EGFR inhibitorsSkin-related toxicities are the most common adverse events associated with EGFR inhibitors The occurrence of grade 2 or higher skin toxicity (ST) has been associated with efficacy in the monotherapy setting 4The occurrence of grade 2 or higher skin toxicity (ST) has been associated with efficacy in the monotherapy setting 4 Here we present the results from the primary analysis and efficacy and patient- reported outcome (PRO) results by ST severityHere we present the results from the primary analysis and efficacy and patient- reported outcome (PRO) results by ST severity

3. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Study Schema and Stratification Tx Arm 1: Panitumumab 6.0 mg/kg Q2W + FOLFIRI Q2W ENROLLMENTENROLLMENTENROLLMENTENROLLMENT ENDENDOFOFTREATMENTTREATMENTENDENDOFOFTREATMENTTREATMENT LONGLONGTERMTERMFOLLOWFOLLOWUPUPLONGLONGTERMTERMFOLLOWFOLLOWUPUP PRO assessments every 4 weeks Disease assessments every 8 weeks Tx Arm 2: FOLFIRI Q2W Study 20050181 Countries United States RussiaJapan FranceBelgium The Netherlands GermanySwitzerlandAustriaItaly Czech Republic SlovakiaPolandLithuania Australia Enrollment Target: 1100 patients Randomization stratification: ECOG score: 0-1 vs. 2 ECOG score: 0-1 vs. 2 Prior oxaliplatin exposure for mCRC Prior oxaliplatin exposure for mCRC Prior bevacizumab exposure for mCRC Prior bevacizumab exposure for mCRC SCREENINGSCREENINGSCREENINGSCREENING UkraineRomaniaBulgaria United Kingdom IrelandPortugalSpainNorwaySwedenFinland

4. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Objectives and Endpoints for Primary Analysis Primary objectives:Primary objectives: –To assess the effect of panitumumab on progression-free survival (PFS) and overall survival (OS) by KRAS mutational status* Co-Primary endpoints (independently tested):Co-Primary endpoints (independently tested): –PFS (by blinded central radiology review) –OS Other key endpoints:Other key endpoints: –Objective response rate (ORR) –Time to progression (TTP) –Duration of response (DOR) –Safety –PRO *KRAS status was determined by blinded, independent central testing

5. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE To evaluate efficacy by worst grade ST (0-1 vs 2-4) according to tumor KRAS status in panitumumab-treated patientsTo evaluate efficacy by worst grade ST (0-1 vs 2-4) according to tumor KRAS status in panitumumab-treated patients PFSPFS OSOS ORRORR –To minimize lead-time bias and under-reporting of ST because of early tx discontinuation, a landmark approach was used that limits the analysis to patients with a PFS time of at least 28 days (when >50% of patients had worst grade ST severity) To evaluate PRO by worst grade ST (0-1 vs 2-4) in patients with WT or mutant (MT) KRAS tumorsTo evaluate PRO by worst grade ST (0-1 vs 2-4) in patients with WT or mutant (MT) KRAS tumors –EQ-5D health state index (HSI) –EQ-5D overall health rating (OHR) Analyses by ST were ad hoc and not pre-specifiedAnalyses by ST were ad hoc and not pre-specified Objectives for Efficacy and PRO Analyses by ST

6. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Key Eligibility Criteria Metastatic adenocarcinoma of the colon or rectumMetastatic adenocarcinoma of the colon or rectum Documented disease progression ≤ 6 months after only 1 prior fluoropyrimidine-based therapy for mCRCDocumented disease progression ≤ 6 months after only 1 prior fluoropyrimidine-based therapy for mCRC No prior EGFR inhibitor therapyNo prior EGFR inhibitor therapy No prior irinotecanNo prior irinotecan Measurable diseaseMeasurable disease Paraffin-embedded tumor tissue available for central biomarker testingParaffin-embedded tumor tissue available for central biomarker testing ECOG performance status of 0 – 2ECOG performance status of 0 – 2 Adequate hematologic, renal, and hepatic functionAdequate hematologic, renal, and hepatic function Signed informed consentSigned informed consent

7. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Statistical Considerations for Efficacy and PRO Analyses by ST ST was defined as any tx emergent adverse event indicative of a skin disorder and represents a composite category of adverse event terms including but not limited to rash, dermatitis acneiform, pruritus, dry skin, skin fissures, and erythemaST was defined as any tx emergent adverse event indicative of a skin disorder and represents a composite category of adverse event terms including but not limited to rash, dermatitis acneiform, pruritus, dry skin, skin fissures, and erythema Retrospective ad-hoc analyses were performed to determine the effect of ST on efficacy and quality-of-life endpointsRetrospective ad-hoc analyses were performed to determine the effect of ST on efficacy and quality-of-life endpoints –PFS (central review) and OS A stratified Cox proportional hazards model was used to examine the relationship between worst grade ST severity (grade 2 - 4 : grade 0 - 1) and time to eventA stratified Cox proportional hazards model was used to examine the relationship between worst grade ST severity (grade 2 - 4 : grade 0 - 1) and time to event –ORR (central review) The ORR by worst grade ST and the common odds ratio for ORR between worst grade ST (grade 2 - 4 : grade 0 - 1) stratified by randomization factors was providedThe ORR by worst grade ST and the common odds ratio for ORR between worst grade ST (grade 2 - 4 : grade 0 - 1) stratified by randomization factors was provided –PRO The primary analyses of the PRO endpoints were performed with the PRO data collected every 4 weeks from baseline to the discontinuation of second-line txThe primary analyses of the PRO endpoints were performed with the PRO data collected every 4 weeks from baseline to the discontinuation of second-line tx A linear mixed model was applied to analyze the changes from baseline PRO score with unstructured covariance and fixed covariates of worst skin toxicity, baseline PRO, study stratification variables (ECOG and prior oxaliplatin or prior bevacizumab) and a random patient effectA linear mixed model was applied to analyze the changes from baseline PRO score with unstructured covariance and fixed covariates of worst skin toxicity, baseline PRO, study stratification variables (ECOG and prior oxaliplatin or prior bevacizumab) and a random patient effect In all PRO assessments, a higher score indicates a better health statusIn all PRO assessments, a higher score indicates a better health status

8. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Results: KRAS Ascertainment Panitumumab + FOLFIRI FOLFIRITotal Patients randomized - n 5915951186 Patients included in KRAS analysis - n (%) 541 (92) 542 (91) 1083 (91) WT KRAS, % WT KRAS, %565455 MT KRAS, % MT KRAS, %444645 KRAS tumor status was determined using the DxS kit (Manchester, UK) that detects the 7 most common KRAS mutations in codons 12 and 13

9. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Demographics and Disease Characteristics for Primary Analysis WT KRAS a (n = 597) MT KRAS a (n = 486) Panitumumab + FOLFIRI (n = 303) FOLFIRI (n = 294) Panitumumab + FOLFIRI (n = 238) FOLFIRI (n = 248) Sex – men - n (%) 188 (62) 191 (65) 133 (56) 148 (60) Age – years, median (min, max) 60 (28, 84) 61 (29, 86) 61 (29, 83) 64 (29, 86) Race, white – n (%) 294 (97) 278 (95) 226 (95) 238 (96) ECOG performance status – n (%) 0-1 288 (95) 273 (93) 224 (94) 233 (94) 2 15 (5) 21 (7) b 14 (6) 15 (6) Primary tumor type – n (%) Colon cancer 187 (62) 189 (64) 156 (66) 164 (66) Rectal cancer 116 (38) 105 (36) 82 (34) 84 (34) Sites of metastatic disease: Liver only 51 (12) 59 (20) 37 (16) 35 (14) Liver + other 220 (73) 189 (64) 166 (70) 172 (69) Other only 47 (16) 44 (15) 34 (14) 39 (16) Missing or unknown 0 (0) 2 (<1) 1 (<1) 2 (<1) Prior oxaliplatin therapy 204 (67) 191 (65) 164 (69) 169 (68) Prior bevacizumab therapy 55 (18) 60 (20) 45 (19) 43 (17) a Demographics and disease characteristics were similarly distributed between treatment arms in the WT/MT KRAS Analysis Sets b Included 1 patient with ECOG 3

10. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE PFS by KRAS Mutation Status (Central Review) HR = 0.73 (95% CI: 0.59, 0.90) Log-rank p-value = 0.004 Events n (%) Median (95% CI) months Panitumumab + FOLFIRI 178/ 303 (59) 5.9 (5.5 - 6.7) FOLFIRI 203/ 294 (69) 3.9 (3.7 - 5.3) WT KRAS MT KRAS HR = 0.85 (95% CI: 0.68, 1.06) Log-rank p-value = 0.14 Events n (%) Median (95% CI) months Panitumumab + FOLFIRI 162/ 238 (68) 5.0 (3.8 - 5.6) FOLFIRI 161/ 248 (65) 4.9 (3.6 - 5.6)

11. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE OS by KRAS Mutation Status WT KRAS MT KRAS HR = 0.94 (95% CI: 0.76, 1.15) Log-rank p-value = 0.55 HR = 0.85 (95% CI: 0.70, 1.04) Log-rank p-value = 0.12 Events n (%) Median (95% CI) months Panitumumab + FOLFIRI 200/ 303 (66) 14.5 (13.0 - 16.0) FOLFIRI 207/ 294 (70) 12.5 (11.2 - 14.2) Events n (%) Median (95% CI) months Panitumumab + FOLFIRI 181/ 238 (76) 11.8 (10.4 - 13.3) FOLFIRI 193/ 248 (78) 11.1 (10.3 - 12.4)

12. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Objective Response by KRAS Status (Central Review) WT KRAS MT KRAS Panitumumab + FOLFIRI (n = 297) FOLFIRI (n = 285) Panitumumab + FOLFIRI (n = 232) FOLFIRI (n = 237) Objective response rate, % (95% CI) 1,2 35 (30 – 41) 10 (7 – 14) 13 (9 – 18) 14 (10 – 19) Complete response 0000 Partial response 35101314 Stable disease 39555549 Progressive disease 18262227 1 For WT KRAS subset: p < 0.001(descriptive); exact test of odds ratio stratified by randomization factors 2 For MT KRAS subset: p = 1.0 (descriptive); exact test of odds ratio stratified by randomization factors All responses were confirmed no earlier than 28 days after the response criteria were first met

13. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Grade 3/4 Adverse Events of Interest Primary Analysis 1 MedDRA = Medical Dictionary for Regulatory Activities 2 There was one grade 5 adverse event of diarrhea in the WT KRAS panitumumab + FOLFIRI group 3 There were 2 grade 5 adverse events of pulmonary embolism in the MT KRAS FOLFIRI group 4 Included cases in which primary cause of death was reported to be disease progression; only 1 panitumumab-related fatal adverse event was reported: ileus WT KRAS (n = 596) MT KRAS (n = 483) Adverse Event by MedDRA 1 – % Panitumumab + FOLFIRI (n = 302) FOLFIRI (n = 294) Panitumumab + FOLFIRI (n = 237) FOLFIRI (n = 246) Patients with any event 73526450 Skin toxicity 372321 Neutropenia20231417 Diarrhea 2 1491411 Stomatitis8394 Pulmonary embolism 3 5232 Dehydration3232 Hypomagnesemia3<150 Paronychia3<130 Febrile neutropenia 2313 Infusion-related reaction (panitumumab) <1-0- Fatal adverse events 4 - % 4675

14. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Distribution of Worst Grade ST Over the Treatment Period WT KRAS MT KRAS Worst Grade 0-1 a Worst Grade 2-4 Worst Grade 0-1 a Worst Grade 2-4 Patients - n (%) 90 (30) 212 (70) 75 (32) 162 (68) Time to worst grade – median (days) 1334.51128 a Time to worst grade only included patients with worst grade 1

15. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Duration of Panitumumab Exposure WT KRAS MT KRAS Worst Grade 0-1 Worst Grade 2-4 Worst Grade 0-1 Worst Grade 2-4 Duration of panitumumab treatment – median (weeks) 12.92510.622.7

16. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Demographics and Disease Characteristics by Worst ST Grade WT KRAS Panitumumab + FOLFIRI MT KRAS Panitumumab + FOLFIRI Worst ST Grade 0 - 1 (n = 90) Worst ST Grade 2 - 4 (n = 212) Worst ST Grade 0 - 1 (n = 75) Worst ST Grade 2 - 4 (n = 162) Sex – men - n (%) 49 (54) 138 (65) 38 (51) 95 (59) Age – years, median (min, max) 62.5 (29, 82) 59 (28, 84) 60 (29, 83) 61 (31, 81) Race, white – n (%) 88 (98) 205 (97) 72 (96) 153 (94) ECOG performance status – n (%) 0 - 1 85 (94) 203 (96) 65 (87) 158 (98) 2 5 (6) 9 (4) 10 (13) 4 (2) Primary tumor type – n (%) Colon cancer 58 (64) 128 (60) 45 (60) 110 (68) Rectal cancer 32 (36) 84 (40) 30 (40) 52 (32) Sites of metastatic disease: Liver only 12 (13) 39 (18) 10 (13) 27 (17) Liver + other 66 (73) 139 (66) 60 (80) 106 (65) Other only 12 (13) 34 (16) 5 (7) 28 (17)

17. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE PFS (Central Assessment) by ST Severity KRAS Safety Set, Panitumumab* WT KRAS MT KRAS HR (Gr 2-4:0-1) = 0.460 (95% CI: 0.340, 0.623) Log-rank p-value <0.0001 HR (Gr 2-4:0-1) = 0.592 (95% CI: 0.447, 0.786) Log-rank p-value = 0.0003 Events n (%) Median (95% CI) months Grade 2-4 172 / 208 (83) 7.4 (6.1 – 8.3) Grade 0-1 74 / 84 (88) 4.5 (3.7 – 6.3) Events n (%) Median (95% CI) months Grade 2-4 152 / 160 (95) 6.0 (5.5 – 7.4) Grade 0-1 68 / 70 (97) 2.8 (2.0 – 3.7) *Landmark analysis among patients with a PFS time ≥ 28 days

18. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE OS by ST Severity KRAS Safety Set, Panitumumab* WT KRAS MT KRAS HR (Gr 2-4:0-1) = 0.408 (95% CI: 0.294, 0.564) Log-rank p-value <0.0001 HR (Gr 2-4:0-1) = 0.415 (95% CI: 0.302, 0.572) Log-rank p-value <0.0001 Events n (%) Median (95% CI) months Grade 2-4 130 / 208 (63) 16.5 (14.7 – 19.5) Grade 0-1 66 / 84 (79) 9.0 (6.7 – 12.2) Events n (%) Median (95% CI) months Grade 2-4 116 / 160 (73) 13.7 (12.5 – 15.0) Grade 0-1 61 / 70 (87) 7.3 (5.3 – 8.6) *Landmark analysis among patients with a PFS time ≥ 28 days

19. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE ORR (Central) by ST Severity KRAS Safety & Central Tumor Response Set* *Landmark analysis among patients with a PFS time ≥ 28 days a Association between severity and objective response rate over study period (ORR) (Odds ratio Grade 2-4 vs. 0-1, adjusted for stratification factors) p = 0.003 a Odds ratio (95% CI) = 2.46 (1.31, 4.61) p = 1.000 a Odds ratio (95% CI) = 1.03 (0.42, 2.72) Panitumumab

20. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Number of pts that Completed the EQ-5D HSI by KRAS and Worst ST (Panitumumab Arm Only) WT KRAS MT KRAS Number of pts at each timepoint - n ST Grade 0 – 1 ST Grade 2 – 4 ST Grade 0 – 1 ST Grade 2 – 4 Baseline7319556149 Week 4 6917455139 Week 8 5917447137 Week 12 4214434109 Week 16 3814427111 Week 20 291242087 Week 24 241131869 Week 28 20781350 Week 32 1875946 Week 36 1560330 Week 40 1045323 Overall compliance for the EQ-5D Health State Index was 65% for patients with WT KRAS and 66% for patients with MT KRAS Overall compliance for the EQ-5D Health State Index was 65% for patients with WT KRAS and 66% for patients with MT KRAS

21. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Number of pts that Completed the EQ-5D OHR by KRAS and Worst ST (Panitumumab Arm Only) WT KRAS MT KRAS Number of pts at each timepoint - n ST Grade 0 – 1 ST Grade 2 – 4 ST Grade 0 – 1 ST Grade 2 – 4 Baseline7219159150 Week 4 6717055137 Week 8 5917248138 Week 12 4314233109 Week 16 3814327112 Week 20 291222086 Week 24 241131870 Week 28 20771350 Week 32 1875945 Week 36 1559330 Week 40 1145222 Overall compliance for the EQ-5D Overall Health Rating was 64% for patients with WT KRAS and 65% for patients with MT KRAS Overall compliance for the EQ-5D Overall Health Rating was 64% for patients with WT KRAS and 65% for patients with MT KRAS

22. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Least Square Mean Difference in HSI Between ST Grade 0-1 vs 2-4 WT KRAS MT KRAS Overall Difference (Gr 0-1 minus 2-4) between two groups: - 0.035 (95% CI: - 0.088, 0.017) Vertical lines = 95% CI Overall Difference (Gr 0-1 minus 2-4) between two groups: 0.009 (95% CI: - 0.051, 0.069) Vertical lines = 95% CI

23. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Least Square Mean Difference in OHR Between ST Grade 0-1 vs 2-4 WT KRAS MT KRAS Overall Difference (Gr 0-1 minus 2-4) between two groups: - 0.676 (95% CI: - 4.555, 3.203) Vertical lines = 95% CI Overall Difference (Gr 0-1 minus 2-4) between two groups: 3.259 (95% CI: - 2.373, 8.892) Vertical lines = 95% CI

24. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE Conclusions This large, randomized trial prospectively analyzed by KRAS status as a predictive biomarker for EGFR treatment in 2 nd -line mCRCThis large, randomized trial prospectively analyzed by KRAS status as a predictive biomarker for EGFR treatment in 2 nd -line mCRC As previously reported, in patients with WT KRAS tumors, panitumumab significantly improved PFS when added to FOLFIRI (median 5.9 vs 3.9 mo; HR = 0.73, p = 0.004)As previously reported, in patients with WT KRAS tumors, panitumumab significantly improved PFS when added to FOLFIRI (median 5.9 vs 3.9 mo; HR = 0.73, p = 0.004) –A trend towards improved overall survival (but not statistically significant) was observed in patients with WT KRAS tumors with panitumumab + FOLFIRI (median 14.5 vs 12.5 mo; HR = 0.85, p = 0.12) –Response rate was improved in patients with WT KRAS tumors with panitumumab + FOLFIRI (35% vs 10%) –Panitumumab was tolerable when administered with FOLFIRI ST grade 2-4 was associated with longer PFS and OS vs ST grade 0-1, regardless of KRAS tumor statusST grade 2-4 was associated with longer PFS and OS vs ST grade 0-1, regardless of KRAS tumor status –This nonrandomized analysis may be confounded by duration of panitumumab exposure and time on study –A definitive conclusion cannot be reached with this exploratory analysis ST grade 2-4 was associated with increased ORR vs ST grade 0-1 only in pts with WT KRAS tumorsST grade 2-4 was associated with increased ORR vs ST grade 0-1 only in pts with WT KRAS tumors When panitumumab is administered in combination with FOLFIRI, there is no overall difference in PRO between pts with WT or MT KRAS experiencing ST grade 2-4 vs ST grade 0-1When panitumumab is administered in combination with FOLFIRI, there is no overall difference in PRO between pts with WT or MT KRAS experiencing ST grade 2-4 vs ST grade 0-1

25. ASCO 2010 CONFIDENTIAL DO NOT DISTRIBUTE References 1.Vectibix ® Prescribing Information, Amgen Inc. Thousand Oaks, CA; 2009 2.Amgen Europe B.V. Vectibix ® Summary of Product Characteristics. 2009 3.Peeters et al: Randomized phase 3 study of panitumumab with FOLFIRI vs FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC) Eur J Cancer Suppl 7:10, 2009 4.Van Cutsem E, et al: Open-Label Phase III Trial of Panitumumab Plus Best Supportive Care Compared With Best Supportive Care Alone in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer. J Clin Oncol 25:1658-1664, 2007