1. Berlin et al. ESMO 2006 Safety and Efficacy of Panitumumab Monotherapy in the Treatment of Metastatic Colorectal Cancer (mCRC) – Summary of Results Across Clinical Studies Jordan Berlin, 1 Eric Van Cutsem, 2 Marc Peeters, 3 J. Randolph Hecht, 4 Michael Wolf, 5 Rafael Amado, 5 Neal J. Meropol 6 Abstract #326O 1 Vanderbilt University Medical Center, Nashville, TN; 2 University Hospital Gasthuisberg, Leuven, Belgium; 3 Ghent University Hospital, Ghent, Belgium; 4 UCLA School of Medicine, Los Angeles, CA; 5 Amgen Inc., Thousand Oaks, CA; 6 Fox Chase Cancer Center, Philadelphia, PA

2. Berlin et al. ESMO 2006 Introduction Panitumumab is a high-affinity (K d = 5  10 −11 M), fully human IgG2 monoclonal antibody directed against EGFr. 1 Panitumumab is a high-affinity (K d = 5  10 −11 M), fully human IgG2 monoclonal antibody directed against EGFr. 1 Panitumumab inhibits EGFr-mediated activity, including EGFr tyrosine autophosphorylation, tumor cell growth, and metastases. 1-4 Panitumumab inhibits EGFr-mediated activity, including EGFr tyrosine autophosphorylation, tumor cell growth, and metastases. 1-4 Panitumumab monotherapy shows clinical activity in patients with late ‑ stage colorectal cancer whose disease progressed after standard irinotecan- and/or oxaliplatin-containing chemotherapy regimens. 5 Panitumumab monotherapy shows clinical activity in patients with late ‑ stage colorectal cancer whose disease progressed after standard irinotecan- and/or oxaliplatin-containing chemotherapy regimens. 5 This summary of five studies presents efficacy data for panitumumab in a total of 732 patients with mCRC who were refractory to prior therapy. Two studies are complete, three are interim. This summary of five studies presents efficacy data for panitumumab in a total of 732 patients with mCRC who were refractory to prior therapy. Two studies are complete, three are interim. 1 Foon et al. Int J Radiat Oncol Biol Phys. 2004;58:984-990. 2 Freeman et al. Eur J Cancer Suppl. 2004;2:95-96. Abstract 313. 3 Freeman et al. Proc Am Assoc Cancer Res. 2005;46:1062. Abstract 4494. 4 Lynch and Yang. Semin Oncol. 2002;29(suppl 9):47-50. 5 Peeters et al. Proc Am Assoc Cancer Res. 2006;47: Abstract CP-1.

3. Berlin et al. ESMO 2006 Objectives Assessment of the efficacy of panitumumab in patients with disease progression during or after prior fluoropyrimidine, irinotecan, and/or oxaliplatin treatment for mCRCAssessment of the efficacy of panitumumab in patients with disease progression during or after prior fluoropyrimidine, irinotecan, and/or oxaliplatin treatment for mCRC Key objectives of the studies included:Key objectives of the studies included: –Objective tumor response –Progression-free survival –Duration of response Secondary objectives of the studies included:Secondary objectives of the studies included: –Time to response –Survival time –Safety (eg, adverse events, skin toxicities, human anti-human antibody responses)

4. Berlin et al. ESMO 2006 Peeters, et al. 2006 a Berlin, et al. 2006 b Hecht, et al. 2006 c Malik, et al. 2005 d Panitumumab(N=229)Crossover(N=177)(N=93)(N=88)(N=150) Phase3 3 (ES) 222 Dose schedule 6 mg/kg Q2W 2.5 mg/kg QW Response assessment RECIST Central review RECIST Local review WHO Central review RECIST Central review Assessment schedule Wks 8-48 and Q3M thereafter until PD Q8W and at investigator discretion Wks 8-48 and Q3M thereafter until PD Q9W and at investigator discretion EGFr staining by IHC, central review ≥ 1% of evaluated tumor cells ≥ 1% of evaluated tumor cells ≥ 10% of evaluated tumor cells <1% (negative) or 1 to < 10% of evaluated tumor cells  High EGFr: 2+ or 3+ in ≥ 10% of tumor cells  Low EGFr: sum of 1+, 2+, and 3+ in ≥ 10%, but 2+ and 3+ in < 10% of evaluated tumor cells Design and Methods a Peeters et al. Proc Am Assoc Cancer Res. 2006;47: Abstract CP-1 b Berlin et al. J Clin Oncol. (Meeting Abstracts). 2006;24:3548 c Hecht et al. J Clin Oncol. (Meeting Abstracts). 2006;24:3547 d Malik et al. J Clin Oncol. (Meeting Abstracts). 2005;23:3520

5. Berlin et al. ESMO 2006 Key Eligibility Criteria Age  18 years Age  18 years ECOG score of 0 – 2 (4 studies) 0 – 1 (1 study) ECOG score of 0 – 2 (4 studies) 0 – 1 (1 study) Pathologic diagnosis of CRC Pathologic diagnosis of CRC Radiographic documentation of disease progression during or within 6 months of most recent chemotherapy of fluoropyrimidine and Radiographic documentation of disease progression during or within 6 months of most recent chemotherapy of fluoropyrimidine and – Irinotecan  65 mg/m 2 /week for 8 weeks and – Oxaliplatin  30 mg/m 2 /week for 6 weeks (4 studies) Prior fluoropyrimidine and irinotecan or oxaliplatin, or both, any exposure; no requirement for documentation of disease progression (1 study: Malik, et al. 2005) Prior fluoropyrimidine and irinotecan or oxaliplatin, or both, any exposure; no requirement for documentation of disease progression (1 study: Malik, et al. 2005) Evaluation of tumor cell EGFr membrane staining (by IHC at central laboratory) Evaluation of tumor cell EGFr membrane staining (by IHC at central laboratory)

6. Berlin et al. ESMO 2006 Patient Disposition All Patients Patients enrolled, n (%) 739 (100) Patients who received study drug, a n (%) 732 (99) Efficacy set, n (%) 617 (84) Median (min, max) follow-up, b weeks All-enrolled analysis set All-enrolled analysis set Efficacy analysis set Efficacy analysis set 56 (3, 151) 64 (16, 151) a Safety set b Follow-up time is calculated from the enrollment date to the date of the data cut-off Results

7. Berlin et al. ESMO 2006 Demographics a ECOG status 3 was reported in 1 panitumumab patient in the phase 3 study Peeters, et al. 2006 Berlin, et al. 2006 Hecht, et al. 2006 Malik, et al. 2005 Panitumumab (N=231) Crossover(N=176)(N=93)(N=88)(N=148) Sex - n (%) Men Men 146 (63) 111 (63) 51 (55) 51 (58) 83 (56) Median (min, max) age - years 62 (55, 68) 62 (32, 83) 59 (31, 82) 62 (26, 85) 60 (21, 88) Race - n(%) White White 229 (99) 175 (99) 74 (80) 71 (81) 120 (81) Black Black 1 (0) 0 (0) 8 (9) 12 (14) 14 (9) Hispanic Hispanic 1 (0) 0 (0) 7 (8) 3 (3) 5 (3) Other Other 0 (0) 1 (1) 4 (4) 2 (2) 9 (6) ECOG status - n (%) a 0 107 (46) 53 (30) 31 (33) 41 (47) 37 (25) 1 94 (41) 85 (48) 55 (59) 42 (48) 111 (75) 2 29 (13) 38 (22) 7 (8) 5 (6) 0 (0)

8. Berlin et al. ESMO 2006 Disease Characteristics Peeters, et al. 2006 Berlin, et al. 2006 Hecht, et al. 2006 Malik, et al. 2005 Panitumumab (N=231) Crossover(N=176)(N=93)(N=88)(N=148) Primary diagnosis, n (%) Colon cancer Colon cancer 153 (66) 113 (64) 70 (75) 61 (69) 106 (72) Rectal cancer Rectal cancer 78 (34) 63 (36) 23 (25) 27 (31) 42 (28) Number of prior lines of chemotherapy, n (%) 231 (100) 176 (100) 93 (100) 88 (100) 65 a (100) 1 1 (0) 0 (0) 2 146 (63) 114 (66) 2 (2) 13 (15) 24 (37) ≥ 3 ≥ 3 84 (36) 62 (35) 91 (98) 75 (85) 41 (63) a Prior chemotherapy is based on a subset of patients who had received fluoropyrimidine, oxaliplatin and irinotecan.

9. Berlin et al. ESMO 2006 Best Objective Response a Modified RECIST criteria; blinded central review b Modified RECIST criteria; local review c Modified WHO criteria; blinded central review All responses were confirmed > 4 weeks after response criteria were first met Disease control rate is the sum of the objective response and stable disease rates Peeters, et al. 2006 Berlin, et al. 2006 Hecht, et al. 2006 Malik, et al. 2005 Panitumumab (N=231) Crossover(N=176)(N=39)(N=23)(N=148) Analysis Set All Enrolled Modified Intent-to- treat Adjud Prior Failure All Enrolled Overall objective response (CR or PR), n (%) 19 (8) a 20 (11) b 3 (8) c 3 (13) c 13 (9) a Stable Disease, n (%) 64 (28) 58 (33) 8 (21) 7 (30) 43 (29) Disease Control 83 (36) 78 (44) 11 (28) 10 (43) 55 (37) PD, n (%) 113 (49) 65 (37) 20 (51) 10 (43) 59 (40)

10. Berlin et al. ESMO 2006 Time and Duration of Response a Objective responses were assessed by blinded central review except for Peeters, et al (2006) crossover study, where the responses were assessed by local review. b Not estimable Peeters, et al. 2006 Berlin, et al. 2006 Hecht, et al. 2006 Malik, et al. 2005 Panitumumab(N=231)Crossover(N=176)(N=39)(N=23)(N=148) Median (range) time to response - weeks a 7.9 (7, 15) 7.7 (7, 25) 11.0 (8, 11) 11.0 (7, 12) 8.1 (7, 25) Median (range) duration of response – weeks 95% CI 17.0 (8, 25) 16.4, 25.3 16.4 (8, 35) 16.0, 23.9 13.2 (12,14) 12.4, 14.0 16.1 (16, 16) NE, NE b 18.1 (8, 36) 17.9, 23.3

11. Berlin et al. ESMO 2006 Progression-Free Survival

12. Berlin et al. ESMO 2006 Progression-Free Survival by Objective Response in the Phase 3 Trial Event-free Probability 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Weeks from Randomization 08162432404856 CR/PR SD Other CR/PR 8% SD 28% Other64% Other=Pts with progressive disease, unevaluable assessments, or no assessments; Groups not comparable due tolead-time bias and lack of randomization. By central review by modified RECIST; responses were confirmed at least 4 weeks after response criteria were first met

13. Berlin et al. ESMO 2006 Progression-Free Survival by Objective Response in the Phase 3 Trial Event-free Probability 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Weeks from Randomization 08162432404856 BSC SD BSC Other Panitumumab CR/PR Panitumumab SD Panitumumab Other CR/PR SD Other Other=Pts with progressive disease, unevaluable assessments, or no assessments; Groups not comparable due to lead-time bias and lack of randomization. By central review by modified RECIST; responses were confirmed at least 4 weeks after response criteria were first met 28%10% 64%90%8%

14. Berlin et al. ESMO 2006 Adverse Events of Interest MedDRA v.8 preferred terms; graded using the NCI CTCAE v 2.0, with the exception of some dermatology/skin adverse events that were graded using the CTCAE v 3.0 with modifications a Safety analysis set b Captured as laboratory values above grade 0 Any (N = 732) Grade 3-4 (N = 732) Subjects with any adverse event a – n (%) Fatigue Fatigue Nausea Nausea Diarrhea Diarrhea Vomiting Vomiting Abdominal Pain Abdominal Pain Constipation Constipation Dyspnea Dyspnea Cough Cough Edema peripheral Edema peripheral Edema Edema Pleural effusion Pleural effusion Deep vein thrombosis Deep vein thrombosis Pulmonary embolism Pulmonary embolism Hypomagnesemia Hypomagnesemia 239 (33) 208 (28) 185 (25) 152 (21) 147 (20) 146 (20) 106 (14) 100 (14) 83 (11) 30 (4) 16 (2) 9 (1) 7 (1) 31 (4) 41 (6) 14 (2) 15 (2) 21 (3) 37 (5) 13 (2) 28 (4) 4 (1) 9 (1) 4 (1) 7 (1) 6 (1) 4 (1) 9 (1) Hypomagnesemia (Lab) b Hypomagnesemia (Lab) b 226 (31) 32 (4)

15. Berlin et al. ESMO 2006 Skin-Related Toxicities Occurring in  10% of Patients MedDRA v.8 preferred terms; graded using the NCI CTCAE v 2.0, with the exception of some dermatology/skin adverse events that were graded using the CTCAE v 3.0 with modifications a Safety analysis set Any (N = 732) Grade 3-4 (N = 732) Subjects with any adverse event a – n (%) Dermatitis acneiform Dermatitis acneiform Pruritus Pruritus Erythema Erythema Rash Rash Skin exfoliation Skin exfoliation Paronychia Paronychia Skin fissures Skin fissures Dry skin Dry skin 669 (91) 382 (52) 379 (52) 384 (52) 263 (36) 145 (20) 142 (19) 115 (16) 99 (14) 95 (13) 36 (5) 13 (2) 33 (5) 20 (3) 10 (1) 8 (1) 5 (1) 1 (0)

16. Berlin et al. ESMO 2006 Infusion reactions Six of 732 (0.8%) patients had infusion reactions of any grade per investigatorSix of 732 (0.8%) patients had infusion reactions of any grade per investigator Two (0.3%) patients had a grade 3 infusion reaction per investigatorTwo (0.3%) patients had a grade 3 infusion reaction per investigator One patient discontinued panitumumab per patient decisionOne patient discontinued panitumumab per patient decision

17. Berlin et al. ESMO 2006 Antibodies to Panitumumab a Acid dissociation ELISA assay Peeters, et al. 2006 Berlin, et al. 2006 Hecht, et al. 2006 Malik, et al. 2005 Total Panitumumab (N=229) Crossover (N=176) (N=91)(N=88)(N=148)(N=732) Samples available for testing, a n 2241529088145699 Baseline samples, n (%) 221 (99) 150 (99) 88 (97) 87 (100) 142 (98) 688 (98) Post-dose samples, n (%) 185 (83) 71 (47) 66 (73) 66 (76) 107 (74) 495 (71) Baseline positive 3 (1) 2 (1) 0 (0) 5 (<1) Post-dose positive 0 (0) 2 (1) 0 (0) 2 (<1)

18. Berlin et al. ESMO 2006 Conclusions Across all studies, panitumumab had consistent antitumor activity in patients with mCRC:Across all studies, panitumumab had consistent antitumor activity in patients with mCRC: –Objective response rates ranged from 8% to 13% –Disease control rates ranged from 28% to 44% –Progression-free survival ranged from 8 to 14 weeks Panitumumab was well toleratedPanitumumab was well tolerated –Of 732 patients, 0.3% had grade 4 skin-related toxicities, and 13% had grade 3 skin-related toxicities –The majority of patients (78%) had grade 1 or 2 skin-related toxicities –Grade 3 infusion reaction rate was 0.3% (there were no grade 4 infusion reactions); premedication was not required –Less than 1% of patients had anti-panitumumab antibodies

19. Berlin et al. ESMO 2006 Conclusions Across all studies, EGFr staining levels were not associated with panitumumab activityAcross all studies, EGFr staining levels were not associated with panitumumab activity There was an association of panitumumab activity with the incidence of skin toxicity (data not shown)There was an association of panitumumab activity with the incidence of skin toxicity (data not shown) Additional studies in mCRC with other agents are ongoingAdditional studies in mCRC with other agents are ongoing

20. Berlin et al. ESMO 2006 Acknowledgements We wish to thank the patients who participated in these studies and their familiesWe wish to thank the patients who participated in these studies and their families We also wish to acknowledge the investigators and research teams who enrolled patientsWe also wish to acknowledge the investigators and research teams who enrolled patients We acknowledge the assistance of Mee Rhan Kim and Geoffrey Smith for slide productionWe acknowledge the assistance of Mee Rhan Kim and Geoffrey Smith for slide production