Exelixis, Inc. · NASDAQ:EXEL
Exelixis — Technical Presentation (October 2011)
19 slides from Exelixis's technical presentation, Oct 26, 2011
Slide 1: Anti-tumor Activity Observed in a Cohort of Patients with Differentiated Thyroid Cancer
Anti-tumor Activity Observed in a Cohort of Patients with Differentiated Thyroid Cancer (DTC) in a Phase 1 Study of Cabozantinib (XL184) Maria E. Cabanillas1, Marcia S. Brose2, David A. Ramies3, Yihua Lee3, Dale Miles3, Steven I. Sherman1 1University of Texas MD Anderson Cancer Center, 2University o
Slide 2: Disclosures
Disclosures • Research funding from Exelixis, Inc. – Maria E. Cabanillas – Marcia S. Brose • Exelixis Personnel – David A. Ramies – Yihua Lee – Dale Miles • Consultant to Exelixis – Steven I. Sherman
Slide 3: DTC Signaling Pathways
DTC Signaling Pathways MET VEGFR RET/PTC PLC-γ Endothelial RAS PKC cell BRAF VEGF PI3K MEK MET AKT ERK Courtesy of Steven I. Sherman-
Slide 4: Cabozantinib
Cabozantinib MET HGF Motility Invasion Metastasis Cabozantinib HIF-1α HIF-1α VEGF Hypoxic Tumor Cell New Blood VEGF targeted Vessels therapies
Slide 5: Trial Design
Trial Design Objectives: -Safety / tolerability of cabozantinib -Anti-tumor activity of cabozantinib Metastatic or unresectable Relapsed or refractory Cabozantinib disease 175 mg daily (N=40) DTC (15) RCC (25)
Slide 6: Key Eligibility Criteria
>18 years of age Metastatic or unresectable DTC (including all variants) Refractory or progressed following standard therapies RAI-refractory RECIST measurable disease Medullary and anaplastic thyroid cancer Untreated brain metastasis or cord compression (°) AMERICAN THYROID ASSOCIATION
Slide 7: Demographics and Baseline Characteristics (N=15)
Demographics and Baseline Characteristics (N=15) Age years Disease Site at Baseline* n (%) Median (range) 53 (42-73) Lung 13 (87) Gender n Bone 9 (60) Male 6 Brain 3 (20) Female 9 Liver 1 (7) ECOG PS n (%) Prior therapies n (%) 0 9 (60) Median prior therapies 2 1 6 (40) (excluding RAI) Diagnosis n (
Slide 8: Most Frequently Reported Related Adverse Events
Most Frequently Reported Related Adverse Events Adverse Event a All Grades, n (%) Grade ≥ 3, n (%) Diarrhea 13 (87) 2 (13) AST Increased 12 (80) 1 (7) Fatigue 12 (80) 0 LDH Increased 10 (67) 1 (7) ALT Increased 9 (60) 1 (7) Nausea 9 (60) 0 Grade 5 T-E fistula with LLL pneumonia in subject with prior
Slide 9: Effects on Measurable Lesions (N=14)
Effects on Measurable Lesions (N=14)a 20 % Change from baseline 0 - 20 ‡ - 40 ‡ ‡ ‡ Papillary ‡ Confirmed PRs ‡ ‡ ‡ - 60 ‡ Follicular SUN Received prior sunitinib Hurthle cell SOR Received prior sorafenib AX Received prior axitinib a One patient was not evaluable for response due to early removal fr
Slide 10: 45-year-old Man with Heavily Pre-treated Hurthle Cell Carcinoma
45-year-old Man with Heavily Pre-treated Hurthle Cell Carcinoma 60 Days BEFORE 20 Days BEFORE 60 Days AFTER treatment treatment treatment Tg = 533,243 Tg = 633,930 Tg = 257,048 RECIST Stable Disease (-11% from baseline) ECOG PS 1 at baseline – has resumed normal activity without restriction
Slide 11: Effects of Cabozantinib on Bone Metastasis
Effects of Cabozantinib on Bone Metastasis
Slide 12: Role for MET and VEGFR in Tumor-Bone Interactions
Role for MET and VEGFR in Tumor-Bone Interactions Osteoblast • Bone metastases in DTC MET HGF are often resistant to anti- VEGF angiogenics • Osteoblasts and osteoclasts express MET and VEGFRs, and MET HGF respond to HGF and VEGF VEGF Osteoclast HGF = Hepatocyte growth factor (MET receptor ligand)
Slide 13: Role for MET and VEGFR in Tumor-Bone Interactions
Role for MET and VEGFR in Tumor-Bone Interactions Osteoblast • HGF and VEGF may be MET HGF key factors mediating VEGF VEGF cross-talk between tumor HGF cells, osteoblasts, and VEGF HGF MET osteoclasts HGF VEGF MET HGF • Simultaneous targeting of VEGF MET and VEGFR may Tumor Cell block progression of
Slide 14: Role for MET and VEGFR in Tumor-Bone Interactions
Role for MET and VEGFR in Tumor-Bone Interactions Osteoblast • HGF and VEGF may be MET HGF key factors mediating VEGF VEGF cross-talk between tumor HGF cells, osteoblasts, and VEGF HGF MET osteoclasts HGF VEGF MET HGF • Simultaneous targeting of VEGF MET and VEGFR may Tumor Cell block progression of
Slide 15: 59-year-old Woman with PTC
59-year-old Woman with PTC RECIST response at week 9 Baseline Week 9 Tg = 11,016 Tg = 1,036
Slide 16: Time on Study Treatment: DTC (N = 15)
Time on Study Treatment: DTC (N = 15) Subjects Bone metastases at baseline Response duration Remain on study treatment 0 10 20 30 40 50 Time (weeks) Median time to response was 8 weeks
Slide 17: Summary of Efficacy (N = 15)
Summary of Efficacy (N = 15) Best objective RR, n (%) Overall Bone Mets (N=9) Partial response (confirmed) 8 (53) 3 (33) Stable disease 6 (40) 5 (56) Progressive disease 0 0 Median Time to Response (days), range 57 (53 - 110) Median Response Duration (days), range N/Ra (58 - 249+) Median Follow-Up (
Slide 18: Summary
Cabozantinib demonstrates encouraging activity in this heavily pretreated DTC population with a high proportion of bone and brain metastases 8/15 PRs (53%), 6/15 SD with regression (40%) All evaluable subjects had tumor regression 12/15 (80%) subjects remain on study Median PFS not reached (only one
Slide 19: Acknowledgements
ACKNOWLEDGEMENTS We thank the patients for their participation in the clinical trial We are grateful to the co-investigators who referred trial patients Research and Data Coordinators 19