1. Initial Results of a Multicenter, Single-Arm Phase 2 Study of AMG 706, an Oral Multikinase Inhibitor, for the Treatment of Advanced Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST) Robert Benjamin, Patrick Schöffski, Jörg Thomas Hartmann, Binh Nguyen Bui, Justus Duyster, Scott Schuetze, Jean-Yves Blay, Peter Reichardt, Lee Rosen, Keith Skubitz, Michael Eschenberg, Daniel Stepan, and Laurence Baker On behalf of the study investigators CTOS Meeting Venice, Italy 4 November 2006

2. CTOS 2006 2 AMG 706: An Oral Multi-targeted Kinase Inhibitor A novel, orally bioavailable, small-molecule multikinase inhibitor Has shown both antiangiogenic and direct antitumor activity in a phase 1 clinical trial in patients with advanced solid tumor malignancies Herbst R et al. Eur J Cancer. 2005;3(Suppl):1455. Rosen L et al. Proc ASCO. 2005. Abstract 3013.

3. CTOS 2006 3 AMG 706 Selectively Targets Multiple Receptor Tyrosine Kinases Involved in Angiogenesis a Stem cell factor

4. CTOS 2006 4 Study Objectives Primary Evaluate the effect of treatment with AMG 706 on the objective response rate (by RECIST) in patients with advanced GIST who developed progressive disease or relapsed while receiving imatinib Secondary Assess effect of AMG 706 on duration of response, progression-free survival, time to progression, survival, and adverse events Explore the utility of 18 FDG-PET and target tumor size/density changes (Choi criteria) for predicting tumor response Assess the pharmacokinetic profiles of AMG 706

5. CTOS 2006 5 Main Eligibility Criteria Histologically confirmed GIST expressing CD117 Documented failure of prior treatment with imatinib –At least 600 mg daily for at least 8 weeks –Disease progression per 2 independently assessed pre-study radiographic scans within 6 months of study day 1 Imatinib treatment terminated at least 7 days before study day 1 Presence of at least one measurable (per RECIST) and progressing tumor lesion not previously treated with radiotherapy or embolization and evaluable by CT or MRI Adequate organ function

6. CTOS 2006 6 Study Design and Treatment Regimen

7. CTOS 2006 7 Study Execution International, multicenter study at 29 sites a –Participating countries (number of patients) USA (64) Germany (34) France (20) Belgium (10) Canada (6) Italy (2) United Kingdom (2) Study accrued 138 patients within 10 months –October 2004 to July 2005 a Screened one or more patients

8. CTOS 2006 8 Baseline Demographics and Clinical Characteristics All Patients N = 138 Men, n (%)84 (61) Age Median (min, max), years ≥ 65 years, n (%) 61 (25, 90) 54 (39) Karnofsky performance, n (%) 100 90 80 70 60 33 (24) 63 (46) 22 (16) 14 (10) 6 (4) Prior chemotherapy other than imatinib, n (%) None 1 regimen ≥ 2 regimens 117 (85) 11 (8) 10 (7) Prior radiotherapy, n (%) None132 (96)

9. CTOS 2006 9 Prior Imatinib Therapy All Patients N = 138 Duration of first imatinib therapy, n (%) ≤ 6 months > 6 months 34 (25) 104 (75) Duration of last imatinib therapy, n (%) ≤ 6 months > 6 months 88 (64) 50 (36) Total duration of imatinib therapy, months median (min, max)32.5 (4.1, 57.3) Best response to most recent imatinib, n (%) Complete response Partial response Stable disease Progressive disease 4 (3) 48 (35) 39 (28) 47 (34)

10. CTOS 2006 10 Maximal Dose of Prestudy Imatinib All Patients N = 138 Highest imatinib dose administered, n (%) 800 mg108 (78) 600 mg21 (15) 1000 mg4 (3) 1200 mg3 (2) 1100 mg1 (1) 700 mg1 (1)

11. CTOS 2006 11 Patient Disposition All Patients N = 138 Completed planned AMG 706 administration (48 wks), n (%)10 (7) Discontinued AMG 706 administration (< 48 wks), n (%) Disease progression Adverse event Consent withdrawn Death Administrative decision Protocol deviation Other 128 (93) 83 (60) 31 (22) 6 (4) 3 (2) 1 (1) 1 (1) 3 (2) Weeks of AMG 706 treatment median (min, max)16 (0.3, 52.0)

12. CTOS 2006 12 Best Tumor Response by RECIST per Independent Review: Per-Protocol Analysis Set a All Patients N = 120 Confirmed RECIST response, n (%)3 (3) 95 % CI0.5, 7.1 Confirmed complete response (CR), n (%) Confirmed partial response (PR), n (%) 0 (0) 3 (3) Stable disease (SD ≥ 52 days), n (%)55 (46) Durable stable disease (SD ≥ 22 weeks), n (%)29 (24) Progressive disease (PD), n (%)39 (33) Unevaluable, n (%)5 (4) Not performed, n (%)18 (15) a Includes all subjects who received at least one administration of AMG 706 and who were classified as having pre-study disease progression (per RECIST) per independent review.

13. CTOS 2006 13 Objective Response by 18 FDG-PET a at Week 8 per Independent Review: Per-Protocol Analysis Set Evaluable b N = 89 All Patients N = 120 Objective response, n (%) 95% CI 27 (30) 21.0, 41.0 27 (23) 15.4, 31.0 Non-response, n (%) 95% CI 62 (70) 59.0, 79.0 93 (78) 69.0, 84.6 a Defined as > 25% decrease in average standardized uptake value (SUV max ) in all RECIST target lesions compared with the average SUV max in all RECIST target lesions at baseline as measured by the independent reviewer. b All patients with a baseline and week 8 18 FDG-PET scan. Does not include patients who discontinue study prior to week 8, even if discontinuation is due to clinical progression.

14. CTOS 2006 14 Objective Response by 18 FDG-PET Screening: 21 June 05 Week 8: 24 August 05

15. CTOS 2006 15 Objective Response by Choi Criteria a at Week 8 per Independent Review: Per-Protocol Analysis Set Evaluable b N = 97 All Patients N = 120 Objective response, n (%) 95% CI 39 (40) 30.3, 50.7 39 (33) 24.2, 41.7 Non-response, n (%) 95% CI 58 (60) 49.4, 69.6 81 (68) 58.3, 75.8 a Defined as ≥ 10% decrease in the sum of the longest diameter of the target lesions (identified by RECIST) and/or ≥ 15% decrease in the average target tumor density (in Hounsfield units, HU) using the RECIST target lesions compared with the average baseline density based on CT scans. b All patients with both baseline and week 8 measures of the sum of the longest diameters (SLD) or tumor density (in HU).

16. CTOS 2006 16 Objective Response by Choi Criteria at Week 8 BaselineWeek 8 HU = 141.4HU = 89.8

17. CTOS 2006 17 Best Response in Tumor Measurement by CT (per RECIST) per Independent Review: Per-Protocol Analysis Set

18. CTOS 2006 18 Progression-Free Survival (PFS) per Independent Review: Per-Protocol Analysis Set

19. CTOS 2006 19 Survival: Per-Protocol Analysis Set

20. CTOS 2006 20 Pharmacokinetic Profiles (Day 1) ParameterNo Gastrectomy Partial or Full Gastrectomy nMean (SD)n t max (hr)*18 0.5 (0.25, 2.0) 8 0.75 (0.25, 4.0) C max (ng/mL)18572 (175)8581 (284) AUC 0-24 (μghr/mL)123.03 (1.94)72.81 (1.37) AUC 0-  (μghr/mL)123.28 (2.23)73.08 (1.47) t 1/2, z (hr)125.80 (1.61)76.77 (2.33) CL/F (L/hr)1254.1 (36.4)759.6 (55.0) C 24 (ng/mL)1224.8 (27.6)725.5 (13.6) Day 1 PK profiles of AMG 706 were similar in patients with partial or full gastrectomy and in patients without gastrectomy. PK profiles of AMG 706 were similar in patients with GIST and in patients with solid tumors (first-in-human study). * Median (range)

21. CTOS 2006 21 Treatment-Emergent Adverse Events Occurring in at Least 15% of Patients All Patients N = 138 Grade 3Grade 4 Diarrhea 76 (55)10 (7)0 Hypertension66 (48)31 (22)1 (1) a Fatigue62 (45)17 (12)0 Nausea48 (35)5 (4)0 Headache47 (34)5 (4)0 Abdominal Pain44 (32)14 (10)0 Anorexia42 (30)10 (7)0 Vomiting41 (30)7 (5)0 Weight decrease37 (27)6 (4)0 Constipation33 (24)2 (1)0 Dysphonia27 (20)00 Asthenia23 (17)7 (5)0 Dizziness22 (16)2 (1)0 Insomnia21 (15)1 (1)0 Data are n (%) a Reversible posterior leukoencephalopathy syndrome

22. CTOS 2006 22 Adverse Events of Interest All Patients N = 138 Grade 3Grade 4Grade 5 Hemorrhage 14 (10)5 (4)1 (1)0 Thromboembolic events a 10 (7)2 (1)4 (3)1 (1) Cardiac disorders a 5 (4)1 (1)2 (1)1 (1) Hypothyroidism b 3 (2)1 (1)00 Impaired wound healing2 (1)1 (1)00 Cholecystitis1 (1)000 Pancreatitis1 (1) 00 Data are n (%) a Two patients experienced both a thromboembolic event and a cardiac disorder b Patients were not monitored with serial TSH levels during the study

23. CTOS 2006 23 Conclusions AMG 706 demonstrated an encouraging clinical benefit rate in study patients with advanced high-dose imatinib-resistant GIST: –Choi response rate of 33% (40% of evaluable patients) –PET response rate of 23% (30% of evaluable patients) –PR (3%) + durable SD ≥ 22 weeks (24%) of 27% –Median progression-free survival of 16 weeks –26-week progression-free survival of 27% –Median survival of 59% AMG 706 was reasonably well tolerated with rare incidence of grade 3/4 adverse events except hypertension. Further studies of AMG 706 in GIST appear warranted.

24. CTOS 2006 24 Acknowledgements All of the participating patients and their families To the global network of investigators, research nurses, study coordinators, and operations staff North America Europe Amgen, Inc. (Sponsor) B Benjamin (14), S Schuetze and L Baker (10), L Rosen (7), K Skubitz (6), D Mahadevan (5), M Fanucchi (5), R Tozer (4), EG Chiorean (3), E Borden (3), A Staddon (2), A Evens (2), R Taub (2), M von Mehran (2), K Mulder (2), B Brockstein (1), A Elias (1), S Chawla (1) JT Hartmann (12), P Schöffski and AT van Oosterom (10), BN Bui (10), J Duyster (10), JY Blay (7), P Reichardt (7), M Flasshove and T Ebeling (5), A Le Cesne (3), I Judson (2), P Casali (1), M Marangolo (1) D Stepan, D Reese, M Eschenberg, Y-N Sun, A Koutsoukos, M MacDonald, W Lovelace, K Aitchison, C Puzo, S Creamer, J Wright, T Juan Radiology Review RadPharm Participating Investigators (Number of Patients Enrolled)