ASCO 2011 Final Results From PRIME: Randomized Phase 3 Study of Panitumumab (pmab) With FOLFOX4 for 1st ‑ line Metastatic Colorectal Cancer (mCRC) Jean Yves Douillard, 1 Salvatore Siena, 2 James Cassidy, 3 Josep Tabernero, 4 Ronald Burkes, 5 Mario E. Barugel, 6 Yves Humblet, 7 David Cunningham, 8 Feng Xu, 9 Kartik Krishnan 9 1 Centre René Gauducheau, Nantes, France; 2 Ospedale Niguarda Ca’ Granda, Milan, Italy; 3 The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom; 4 Vall d'Hebrón University Hospital, Barcelona, Spain; 5 Mount Sinai Hospital, Toronto, Canada; 6 Hospital de Gastroenterología, Buenos Aires, Argentina; 7 Centre du Cancer de l'Université Catholique de Louvain, Brussels, Belgium; 8 The Royal Marsden NHS Foundation Trust, London, United Kingdom; 9 Amgen Inc., Thousand Oaks, California;

ASCO 2011 Disclosures Compensation from Amgen for:Compensation from Amgen for: –Steering Committee chairperson –Advisory Board participation –Symposia presentations

ASCO 2011 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 tumor status 1Panitumumab, 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 tumor status 1 PRIME ( ) was an open-label, randomized, global, phase 3 trial prospectively investigating panitumumab with FOLFOX4 vs FOLFOX4 alone as 1st-line treatment (tx) for mCRC among patients with WT KRAS tumors PRIME ( ) was an open-label, randomized, global, phase 3 trial prospectively investigating panitumumab with FOLFOX4 vs FOLFOX4 alone as 1st-line treatment (tx) for mCRC among patients with WT KRAS tumors The results from the primary analysis of this study showed that panitumumab + FOLFOX4 was generally tolerable and significantly improved progression-free survival (PFS) in patients with WT KRAS mCRC vs FOLFOX4 alone 3The results from the primary analysis of this study showed that panitumumab + FOLFOX4 was generally tolerable and significantly improved progression-free survival (PFS) in patients with WT KRAS mCRC vs FOLFOX4 alone 3 This prespecified final descriptive analysis of PFS and overall survival (OS) was planned for approximately 30 months after the last patient was enrolledThis prespecified final descriptive analysis of PFS and overall survival (OS) was planned for approximately 30 months after the last patient was enrolled 1 Amgen Europe B.V. Vectibix ® Summary of Product Characteristics; Vectibix ® Prescribing Information, Amgen Inc. Thousand Oaks, CA; Douillard JY, et al. J Clin Oncol. 2010; 28:

ASCO 2011 Study Objective and Endpoints Primary Objective:Primary Objective: –To assess the effect of panitumumab on PFS by tumor KRAS status* Primary Endpoint:Primary Endpoint: –PFS (by blinded central radiology review) Other Endpoints:Other Endpoints: –OS –Objective response rate (ORR) –Time to progression (TTP) –Duration of response (DOR) –Patient reported outcomes –Safety *KRAS status was determined by blinded, independent, central testing

ASCO 2011 Key Eligibility Criteria Metastatic adenocarcinoma of the colon or rectumMetastatic adenocarcinoma of the colon or rectum No prior tx for mCRCNo prior tx for mCRC –Adjuvant 5-FU-based therapy was allowed if disease recurrence occurred > 6 months after completion –Prior oxaliplatin was not allowed No prior EGFR inhibitor therapyNo prior EGFR inhibitor therapy Measurable diseaseMeasurable disease Paraffin-embedded tumor tissue available for central biomarker testingParaffin-embedded tumor tissue available for central biomarker testing –EGFR expression and KRAS status were not required at entry ECOG performance status 0 - 2ECOG performance status Adequate hematologic, renal, and hepatic functionAdequate hematologic, renal, and hepatic function Signed informed consentSigned informed consent

ASCO 2011 Statistical Considerations Primary Analysis The primary PFS and OS analysis are complete and were previously reported 1The primary PFS and OS analysis are complete and were previously reported 1 Final Analysis The final OS analysis was planned for up to ~ 30 months after the last patient was randomizedThe final OS analysis was planned for up to ~ 30 months after the last patient was randomized This occurred subsequent to the primary analysesThis occurred subsequent to the primary analyses No formal hypothesis testing of efficacy or safety endpoints were plannedNo formal hypothesis testing of efficacy or safety endpoints were planned Descriptive estimates of key comparative efficacy and safety analyses were to be updated to assess the overall relative treatment profileDescriptive estimates of key comparative efficacy and safety analyses were to be updated to assess the overall relative treatment profile 1 Douillard JY, et al. J Clin Oncol. 2010; 28:

ASCO 2011 Demographics and Disease Characteristics Final Analysis WT KRAS MT KRAS Panitumumab + FOLFOX4 (n = 325) FOLFOX4 (n = 331) Panitumumab + FOLFOX4 (n = 221) FOLFOX4 (n = 219) Sex – Men, % Age – years, median (min, max) 62 (27, 85) 61 (24, 82) 63 (33, 83) 61 (27, 82) Race – White, % ECOG performance status, % Region, % Western EU, Canada, Australia Primary Diagnosis, % Colon cancer Colon cancer Rectal cancer Rectal cancer Prior adjuvant, % Sites of metastatic disease, % Liver only Liver + other sites Median follow-up time, months

ASCO 2011 PFS by KRAS Mutation Status Final Analysis Events n (%) Median (95% CI) months Panitumumab + FOLFOX4 270 / 325 (83) 10.0 (9.3 – 11.4) FOLFOX4 280 / 331 (85) 8.6 (7.5 – 9.5) HR = 0.80 (95% CI: 0.67 – 0.95) Log-rank p-value = 0.01 Events n (%) Median (95% CI) months Panitumumab + FOLFOX4 204 / 221 (92) 7.4 (6.9 – 8.1) FOLFOX4 196 / 219 (89) 9.2 (8.1 – 9.9) HR = 1.27 (95% CI: 1.04 – 1.55) Log-rank p-value = 0.02 WT KRAS MT KRAS

ASCO 2011 On-Treatment* PFS by KRAS Mutation Status Final Analysis Events n (%) Median (95% CI) months Panitumumab + FOLFOX4 212 / 325 (65) 9.9 (9.2 – 11.3) FOLFOX4 234 / 331 (71) 8.0 (7.5 – 9.4) HR = 0.77 (95% CI: 0.63 – 0.92) Treatment effect p-value = Events n (%) Median (95% CI) months Panitumumab + FOLFOX4 157 / 221 (71) 7.3 (6.3 – 7.9) FOLFOX4 155 / 219 (71) 8.9 (7.6 – 9.4) HR = 1.32 (95% CI: 1.05 – 1.65) Treatment effect p-value = WT KRAS MT KRAS *From randomization to the date of first disease progression or death within 60 days after the last evaluable tumor assessment or randomization, whichever was later

ASCO 2011 OS by KRAS Mutation Status Final Analysis Events n (%) Median (95% CI) months Panitumumab+ FOLFOX4 214 / 325 (66) 23.9 ( ) FOLFOX4 231 / 331 (70) 19.7 ( ) HR = 0.88 (95% CI: 0.73 – 1.06) Log-rank p-value = 0.17 Events n (%) Median (95% CI) months Panitumumab+ FOLFOX4 179 / 221 (81) 15.5 ( ) FOLFOX4 177 / 219 (81) 19.2 ( ) HR = 1.17 (95% CI: 0.95 – 1.45) Log-rank p-value = 0.15 WT KRAS MT KRAS

ASCO 2011 Post Protocol Treatment WT KRAS MT KRAS Panitumumab + FOLFOX4 (n = 325) FOLFOX4 (n = 331) Panitumumab + FOLFOX4 (n = 221) FOLFOX4 (n = 219) Patients receiving anti- EGFR therapy after treatment phase - n (%) 42 (13) 84 (25) 15 (7) 36 (16) Time from randomization to subsequent anti-EGFR therapy - Median (months) Patients receiving IRI, OX, or 5-FU CT after treatment phase - n (%) 191 (59) 214 (65) 133 (60) 153 (70) Time from randomization to subsequent IRI, OX, or 5-FU CT - Median (months) IRI: irinotecan; OX: oxaliplatin; 5-FU: fluoropyrimidine; CT: chemotherapy

ASCO 2011 Objective Response by KRAS Status (Central Review) WT KRAS MT KRAS Panitumumab + FOLFOX4 (n = 317) a FOLFOX4 (n = 324) a Panitumumab + FOLFOX4 (n = 215) a FOLFOX4 (n = 211) a Objective response rate, % (95% CI) 57 (51 – 63) 48 (42 – 53) 40 (33 – 47) 41 (34 – 48) Odds ratio (95% CI) b 1.47 (1.07 – 2.04) p = (0.65 – 1.47) p = 0.92 Complete response, % <1<100 Partial response, % Stable disease, % Progressive disease, % a Included only patients with baseline measurable disease per central review b Adjusted for geographic region and ECOG performance status score All responses were required to be confirmed at least 28 days after the response criteria were first met

ASCO 2011 WT KRAS: Primary Vs Final Analysis Primary Analysis Final Analysis Panitumumab + FOLFOX4 (n = 325) FOLFOX4 (n = 331) Panitumumab + FOLFOX4 (n = 325) FOLFOX4 (n = 331) Median PFS (m) PFS Hazard Ratio (95% CI) 0.80 ( ) p = ( ) p = 0.01 Median OS (m) OS Hazard Ratio (95% CI) 0.83 ( ) p = ( ) p = 0.17 Objective response rate (ORR) 55%48%57%48% ORR p-value p = 0.07 p = 0.02 Subsequent EGFR use 8%18%13%25%

ASCO 2011 Final Analysis Panitumumab + FOLFOX4 (n = 325) FOLFOX4 (n = 331) Objective response rate 1 57%48% Patients with liver-only metastases at baseline – n (%) 61 (19) 57 (17) Patients with complete liver resection – n (% [95% CI]) 17 (28% [ ]) 10 (18% [ ]) Complete Resection Rate for Patients With WT KRAS Tumors and Liver-only Disease 1 Included only patients with baseline measurable disease per central review

ASCO 2011 Events n (%) Median months Liver complete resection 3 / 27 (11) Not Reached (NA) No liver complete resection 54 / 91 (59) 23.6 ( ) OS Following Complete Resection for Patients With Liver-Only Metastases and WT KRAS mCRC

ASCO 2011 Grade 3/4 Adverse Events of Interest Final Analysis 1 MedDRA = Medical Dictionary for Regulatory Activities; 2 No grade 4 infusion reactions WT KRAS MT KRAS Adverse Event by MedDRA 1 – % Panitumumab + FOLFOX4 (n = 322) FOLFOX4 (n = 327) Panitumumab + FOLFOX4 (n = 217) FOLFOX4 (n = 218) Patients with any event Neutropenia Skin toxicity Diarrhea Neurologic toxicity Hypokalemia10594 Fatigue10375 Mucositis9<163 Hypomagnesemia7<16<1 Paronychia 3020 Pulmonary embolism 3234 Febrile neutropenia 2233 Investigator-reported infusion reaction (panitumumab) 2 <1-0- Fatal adverse events - % 5683

ASCO 2011 PFS, OS, and Objective Response by Worst Grade Skin Toxicity in Patients With WT KRAS Tumors Receiving Panitumumab* * Landmark analysis among patients with a PFS time ≥ 28 days Events n (%) Median (95% CI) months Grade / 250 (83) 11.3 (9.9 – 13.2) Grade / 64 (86) 6.1 (5.3 – 9.2) HR (Gr 2-4: 0-1) = 0.56 (95% CI: 0.41 – 0.76) Log-rank p-value = Skin Toxicity Worst Grade 0-1 (n = 61) Skin Toxicity Worst Grade 2-4 (n = 246) Objective response rate, % (95% CI) 41 (29 – 54) 63 (57 – 69) Odds Ratio (95% CI) 2.55 (1.36, 4.80) p-value p = HR (Gr : 0 - 1) = 0.53 (95% CI: ) p-value = Events n (%) Median (95% CI) months Grade / 250 (63) 27.7 (23.8 – 30.8) Grade / 64 (78) 11.5 (9.1 – 20.2) PFSOS Median (Q1, Q3) time to worst grade 2 or greater skin toxicity was 53 (13, 118) daysMedian (Q1, Q3) time to worst grade 2 or greater skin toxicity was 53 (13, 118) days

ASCO 2011 Conclusions In the final analysis of PRIME, panitumumab plus FOLFOX4 vs FOLFOX4 in patients with WT KRAS mCRC showed:In the final analysis of PRIME, panitumumab plus FOLFOX4 vs FOLFOX4 in patients with WT KRAS mCRC showed: –Statistically significant improvement in PFS –Trend toward improved OS –Statistically significant improvement in response rate A quarter of patients with WT KRAS enrolled in the FOLFOX4 “alone” arm received subsequent anti-EGFR therapy after the protocol treatment phase was complete but before the final efficacy analyses, likely affecting OS resultsA quarter of patients with WT KRAS enrolled in the FOLFOX4 “alone” arm received subsequent anti-EGFR therapy after the protocol treatment phase was complete but before the final efficacy analyses, likely affecting OS results In patients with MT KRAS tumors, outcomes were inferior for panitumumab + FOLFOX4 vs FOLFOX4 aloneIn patients with MT KRAS tumors, outcomes were inferior for panitumumab + FOLFOX4 vs FOLFOX4 alone Adverse event rates were consistent with the primary analysis and as expected for an EGFR inhibitorAdverse event rates were consistent with the primary analysis and as expected for an EGFR inhibitor In patients receiving panitumumab with WT KRAS mCRC who develop grade 2–4 skin toxicity, PFS, OS, and objective response are improved vs patients with skin toxicity grade 0–1In patients receiving panitumumab with WT KRAS mCRC who develop grade 2–4 skin toxicity, PFS, OS, and objective response are improved vs patients with skin toxicity grade 0–1

ASCO 2011 Acknowledgements The authors wish to thank:The authors wish to thank: –The patients and their families that participated in this trial –The investigators and their study staff worldwide for their participation in the conduct and reporting of this study –The study team at Amgen