Disclosures

1. A Randomized, Phase Ib/II Trial of Rilotumumab(AMG 102; ril) or Ganitumab (AMG 479; gan) With Panitumumab (pmab) vsPmab Alone in Patients With Wild-Type (WT) KRAS Metastatic Colorectal Cancer (mCRC): Primary and Biomarker Analyses Cathy Eng,1 Eric Van Cutsem,2Elzbieta Nowara,3 Anna Świeboda-Sadlej,4 Niall C. Tebbutt,5 Edith Mitchell,6 Irina Davidenko,7Kelly S. Oliner,8 Lisa Chen,8 Jing Huang,9 Ian McCaffery,8Elwyn Loh,9 Dominic Smethurst,10 Josep Tabernero11 1The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA; 2University Hospital Gasthuisberg, Leuven, Belgium; 3Instytut im. M. Sklodowskiej-Curie, Gliwice, Poland; 4Warszawski UniwersytetMedyczny, Warszawa, Poland; 5Austin Hospital, Heidelberg, VIC, Australia; 6Thomas Jefferson University, Philadelphia, PA; 7Krasnodar City Oncology Center, Krasnodar, Russia; 8Amgen Inc., Thousand Oaks, CA, USA; 9Amgen Inc., South San Francisco, CA, USA; 10Amgen Ltd., London, UK; 11Vall d'Hebron University Hospital, Barcelona, Spain

2. Disclosures • Cathy Eng: Research funding from Keryx, Daiichi, and Amgen Inc.; paid consultant for Genentech and Amgen Inc.

3. Introduction • Panitumumab, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFR), has demonstrated efficacy in patients with wild-type KRAS mCRC in clinical trials1-4 • Rilotumumab (AMG 102) and ganitumab (AMG 479) are investigational, fully human monoclonal antibodies against the hepatocyte growth factor (HGF; ligand for c-Met receptor) and the insulin‑like growth factor 1 receptor (IGF-1R), respectively • Preclinical studies indicate that there is complex interdependence between the HGF/c-Met and IGF-1R and EGFR pathways5-10 • Combinations of agents that block these receptors are being investigated for their potential to generate additive/synergistic anticancer effects 1. Van Cutsem E, et al. J ClinOncol. 2007;25:1658-1664. 2. Amado RG, et al. J ClinOncol. 2008;26:1626-1634. 3. Peeters M, et al. J ClinOncol. 2010;28:4706-4713. 4. Douillard JY, et al. J ClinOncol. 2010;28:4697-4705. 5. Lesko E, et al. Front Biosci. 2008;13:1271-1280. 6. Hynes NE, et al. Nat Rev Cancer. 2005;5:341-354. 7. Jo M, et al. J Biol Chem. 2000;275:8806-8811. 8. Ahmad T, et al. J Biol Chem. 2004;279:1713-1719. 9. Roudabush FL, et al. J Biol Chem. 2000;275:22583-22589. 10. Swantek JL, et al. Endocrinology. 1999;140:3163-3169.

4. Rilotumumab (AMG 102) and Ganitumab(AMG 479) Mechanisms of Action Rilotumumab ( ) Rilotumumab (AMG 102) targets HGF, inhibiting downstream c-Met signaling Ganitumab (AMG 479) targets IGF-1R, inhibiting downstream signaling through PI3K/AKT and MAPK pathways

5. Study Schema • Amgen Trial 20060447; ClinicalTrials.gov identifier NCT00788957 Part 1 (Phase 1b)a Part 2 (Phase 2)b Part 3 (Phase 2)c Panitumumab+ Rilotumumab(AMG 102) Q2W R A N D O M I Z E R A N D O M I Z E Panitumumab+ Rilotumumab(AMG 102) Q2W Rilotumumab (AMG 102) Q2W Panitumumab+ Ganitumab(AMG 479) Q2W Ganitumab (AMG 479) Q2W Panitumumab+ Placebo Q2Wd aPanitumumab 6 mg/kg Q2W; rilotumumab (AMG 102) 10 mg/kg Q2W with dose de-escalation to 5 mg/kg as necessary; primary endpoint was incidence of dose-limiting toxicities bPanitumumab 6 mg/kg Q2W; rilotumumab (AMG 102) dose based on phase 1b; ganitumab (AMG 479) 12 mg/kg Q2W; primary endpoint was ORR cRilotumumab 10 mg/kg Q2W; ganitumab (AMG 479) 12 mg/kg Q2W; primary endpoint was ORR dPatients in the placebo arm of Part 2 with progressive disease or intolerance to treatment were eligible to participate in Part 3 DLT, dose-limiting toxicity; ORR, objective response rate; Q2W, every 2 weeks • Tumor assessments were performed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0

6. Study Objectives Primary Objectives (Part 2) • To evaluate the efficacy as measured by the objective response rate (ORR) of rilotumumab (AMG 102) + panitumumab and ganitumab (AMG 479) + panitumumab vspanitumumab + placebo Other Key Objectives (Part 2) • Efficacy including progression-free survival (PFS) and overall survival (OS) • Safety • Pharmacokinetic analysis • Biomarker analysis

7. Key Eligibility Criteria • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 • Histologically or cytologically confirmed wild-type KRAS mCRC by local or central testing • Progression during or following prior treatment with irinotecan- and/or oxaliplatin-based chemotherapy for mCRC • Glycosylated hemoglobin < 8% • No prior treatment with EGFR, c-Met, or IGF-1R inhibitors

8. Statistical Considerations for Part 2 • Randomization was stratified by prior therapy (oxaliplatin or irinotecan vs both) • Bayesian analysis of ORR • This method compares the posterior distribution for the experimental arms to that of the control arm to determine an Odds Ratio • A prior distribution for panitumumabmonotherapy was derived from 4 previous trials (wild-type KRAS and ECOG 0/1) • The prior distributions for the combination arms were assumed to have the same mean as the panitumumab alone arm • The posterior distribution for each arm combines the prior distributions with observed ORRs from the study • It was prespecified that if there was ³ 90% probability that combination therapy was better than panitumumab alone as evaluated by objective tumor response, the combination was to be considered promising • If there was between 50% and 90% probability, the combination was to be considered indeterminate • If there was < 50% probability, the combination was to be considered not promising

9. Results for Part 2 • 142 patients enrolled from 37 sites in 11 countries • The enrollment period was June 9, 2009 through February 5, 2010 • The date for data cut-off for this analysis was July 23, 2010 • Median follow-up is 6.9 months; follow-up is ongoing

10. Part 2: Patient Demographics and Disease Characteristics at Baseline aOne patient with ECOG performance score of 2 was enrolled in error; data from this patient were included in all efficacy and safety analyses bTwo patients had not received first-line therapy for mCRC; both patients had received oxaliplatin-based chemotherapy for non-metastatic CRC in the adjuvant setting and progressed on therapy before entering the study

11. Primary Endpoint:Objective Response Rate aThe minimum assessment time must be at least 49 days from the first dosing date to be qualified as stable disease bDisease control rate = CR + PR + SD cOR is calculated based on ORR; an OR > 1 favors the combination arm over panitumumab alone NE, not estimable • Responses were required to be confirmed at least 4 weeks after response criteria were first met

12. Patient in Study 20060447 Baseline 1st Restaging

13. Progression-Free Survival Panitumumab ± Rilotumumab (AMG 102) (AMG 102) (AMG 102) Panitumumab ± Ganitumab (AMG 479) (AMG 479) (AMG 479)

14. Adverse Events (Any Grade in ³ 20% or Grade 3/4 in ³ 2 Patients) AE, adverse event • There were 9 grade 5 AEs; 1 occurred in the panitumumab alone arm and 4 occurred each in the combination arms • All except 1 were due to disease progression; 1 fatal AE was due to staphylococcal sepsis (panitumumab + ganitumab [AMG 479] arm) • None were reported to be related to investigational product

15. Biomarker Analysis of c-Met Expression in Patients Receiving Panitumumab ± Rilotumumab (AMG 102) • c-Met expression was measured by immunohistochemistry (IHC) on archival tumor samples • ~15% of the archival tumor samples were from metastatic lesions (12% liver, 3% lung) • Samples were scored for c-Met expression with a staining intensity between 0 and 3 • To determine the percentage of tumor cells expressing c-Met in a sample, tumor cells with a staining intensity of at least 1 were considered positive • High c-Met expression = Positive tumor cells > 50% • Low c-Met expression = Positive tumor cells £ 50% • 91 of 96 patients receiving panitumumab ± rilotumumab (AMG 102) had c-Met IHC results • For PFS, a Cox proportional hazards model was used • For objective response, a Logistic Regression model was used • Models are adjusted for randomization by prior therapy (oxaliplatin or irinotecanvs both)

16. Effect of Cytoplasmic c-Met IHC Stainingon Objective Response Rate # of Patients(# of Events) c-Met IHCParameter TreatmentGroup Low Expression HighExpression InteractionP-value OR (95% CI) P-value AMG 102 + Pmab26 (6) 21 (9) 2.501 (0.712-8.789) 0.153 0.916 Placebo + Pmab26 (4) 18 (6) 2.777 (0.648-11.903) 0.169 NA High = % Pos > 50%* Low = % Pos ≤ 50% AMG 102 + Pmab35 (8) 12 (7) 4.975 (1.194-20.729) 0.028 0.446 Placebo + Pmab32 (6) 12 (4) 2.187 (0.486-9.830) 0.308 NA High = Max SI ≥ 2+ Low = Max SI < 2+ 0.01 0.1 0 10 100 Favors LowExpression Favors HighExpression *Positive tumor cells are those with a staining intensity of at least 1 IHC, immunohistochemistry; OR, odds ratio; Pmab, panitumumab; SI, staining intensity; Pos, positive

17. Effect of Cytoplasmic c-Met IHC Staining on Progression-Free Survival Panitumumab + Rilotumumab (AMG 102) Panitumumab + Placebo High expression = % Positive > 50%* Low expression = % Positive £ 50% *Positive tumor cells are those with a staining intensity of at least 1

18. Conclusions • This is the first study to show promising evidence of efficacy by an HGF (c-Met pathway) inhibitor (rilotumumab [AMG 102]) when combined with panitumumab in patients with KRASWT mCRC. • The activity as assessed by ORR for patients receiving rilotumumab (AMG 102) plus panitumumab is promising (per prospectively specified Bayesian criterion). • Efficacy of ganitumab (AMG 479) plus panitumumab combination therapy as determined by ORR was indeterminate. • The safety profiles of the drug combinations were generally similar to that of panitumumab alone with some exceptions, including a higher rate of grade 3/4 rash with rilotumumab (AMG 102) and of hypomagnesemia with ganitumab (AMG 479). • Cytoplasmic c-Met expression by IHC may not be definitive for predictive benefit for rilotumumab (AMG 102).