Exelixis, Inc. · NASDAQ:EXEL
Exelixis — ASCO GU Symposium 2011
58 slides from Exelixis's conference presentation, Feb 17, 2011
Slide 1: Exelixis Investor Update
Exelixis Investor Update ASCO GU Symposium February 17, 2011
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains certain statements that are forward-looking, including, without limitation, statements relating to Exelixis’ belief that cabozantinib is the primary value driver for the company, the continued development and clinical, therapeutic and commercial
Slide 3: Michael Morrissey, PhD, President and CEO
Michael Morrissey, PhD President and CEO
Slide 4: Encouraging Cabozantinib CRPC Data at ASCO-GU
Encouraging Cabozantinib CRPC Data at ASCO-GU Clinical activity in both bone and soft tissue metastatic lesions in CRPC • Overall disease control rate at week 12 is 74% • Bone scan resolution (complete or partial) in 53 of 62 (85%) or stabilization in 8 of 62 patients (13%) associated Improvement in
Slide 5: Today's Agenda
Today’s Agenda Welcome & Overview Dr. Michael Morrissey Cabozantinib Overview and Data Review Experience at Dana Farber Dr. Philip Kantoff ASCO GU Data in mCRPC Dr. Matthew Smith Dr. Ron Weitzman Clinical Development Plan Dr. Howard Scher Closing and Q&A Dr. Michael Morrissey 5
Slide 6: Key Milestones for Cabozantinib in 1H 2011
Key Milestones for Cabozantinib in 1H 2011 ASCO GU – CRPC data ASCO Annual Meeting • CRPC • Ovarian cancer • Other RDT indications • Renal cell carcinoma Readout MTC top-line data • Phase 3 readout expected in 1H 2011 • NDA filing planned for 2H 2011 IMPORTANT 1H 2011 MILESTONES DRIVING NEWS FLOW 6
Slide 7: Philip Kantoff MD, Dana-Farber Cancer Institute
Philip Kantoff MD Dana-Farber Cancer Institute Professor of Medicine Harvard Medical School 7
Slide 8: Prostate Cancer Landscape: February 2010
Prostate Cancer Landscape: February 2010 Hormone Sensitive Newly diagnosed Rising PSA, Metastatic Localized disease No mets Hormone-naïve Surgery ADT or ADT Radiation observation Castration Resistant Metastatic, Metastatic, Metastatic, Non-metastatic Chemotherapy-naïve Chemotherapy-naïve Asymptomati
Slide 9: Prostate Cancer Landscape: February 2011
Prostate Cancer Landscape: February 2011 Hormone Sensitive Newly diagnosed Rising PSA, Metastatic Localized disease No mets Hormone-naïve Surgery ADT or ADT Radiation observation Active Surveillance Castration Resistant Metastatic, Metastatic, Metastatic, Non-metastatic Chemotherapy-naïve Chemothera
Slide 10: Changing Landscape in 2011
Changing Landscape in 2011 • New agents in 2011 Abiraterone-likely FDA approval in docetaxel treated CRPC • Denosumab may delay development of bone metastases 10
Slide 11: Beyond 2011?
Beyond 2011? • Abiraterone in docetaxel naïve CRPC • MDV3100 in post-docetaxel CRPC • MDV3100 in pre-docetaxel CRPC • Other CYP17 lyase inhibitors TAK700 TOK001 • Other antiandrogens ARN-509 • Biologics combined with docetaxel Many • Immunotherapeutics Anti-CTLA-4 and PD-1 Prostvac-VF Tr
Slide 12: Cabozantinib (XL184)
Cabozantinib (XL184) • Small molecule tyrosine kinase inhibitor • Known spectrum of kinase activity (IC50 < 20nM) • VEGFR2, MET, KIT, RET, AXL, Tie2, FLT3 12
Slide 13: Broad Anti-tumor Activity Across Multiple Tumor Types
Broad Anti-tumor Activity Across Multiple Tumor Types 39 PRs in 269 pts with ≥ 1 post-baseline assessment (N = 269) Effects in bone Courtesy of Exelixis 13
Slide 14: CRPC: Anti-Tumor Activity in Bone and Soft Tissue
CRPC: Anti-Tumor Activity in Bone and Soft Tissue Baseline Week 6 Prior Docetaxel Yes Maximum tumor change, per –26% mRECIST Improvement in bone painb Yes Change in tALP and PSA N/A, not available; NE, not evaluated due to no pain at baseline; PSA, prostate specific antigen; BL, Baseline Bone scans
Slide 15: What is the Mechanism of this Major Bone Activity?
What is the Mechanism of this Major Bone Activity?
Slide 16: Cabozantinib (XL184)
Cabozantinib (XL184) Bone metastases represent a major unmet medical need in oncology • Bone metastases occur in ~300K cancer patients in the US annually • Most common with prostate, breast & lung cancer & multiple myeloma • Strong preclinical data supporting the bone activity of cabozantinib Vehicl
Slide 17: Cabozantinib Targets Key Cell Types in Metastatic Bone Lesions
Cabozantinib:Targets 3 Key Cell Types in Metastatic Bone Lesions Cabozantinib Bone Destruction Bone Formation Tumor Cells Osteoclasts Osteoblasts TUMOR CELLS, OSTEOBLASTS & OSTEOCLASTS EXPRESS ACTIVATED MET & VEGFR 17
Slide 18: Is MET Inhibition VEGFR2 Inhibition or Both Important?
Is MET Inhibition VEGFR2 Inhibition or Both Important?
Slide 19: Up-regulation of MET as a Response to Treatment
Up-regulation of MET as a Response to Treatment VEGF Pathway Androgen Receptor Inhibition Blockade EGFR Inhibition Hypoxia, HIF1 stabilization Selection for MET amplification Relief of AR-mediated Up-regulation of MET (NSCLC) repression (Prostate) MET Expression 19
Slide 20: Is this Bone Effect Specific to CRPC?
Is this Bone Effect Specific to CRPC?
Slide 21: Cabozantinib Activity in Bone Lesions Extends Beyond CRPC
Cabozantinib Activity in Bone Lesions Extends Beyond CRPC • Effects in Bone observed in − CRPC − Breast Cancer − Melanoma − Thyroid Cancer − Renal Cell Cancer Resolution of Bone Scan Lesions often Accompanied by Pain Relief 21
Slide 22: Bone Scan Change in Subject with ER/PR+ Metastatic Breast Cancer
Bone Scan Change in Subject with ER/PR+ Metastatic Breast Cancer Prior Treatment 1. Adjuvant AC 2. Adjuvant Tam 3. Arimidex 4. Faslodex 5. Ixabepilone 29% shrinkage in target lesions (improvement in pain) 22 Baseline Week 6
Slide 23: Bone Scan Changes in Renal Cell Carcinoma
Bone Scan Changes in Renal Cell Carcinoma Baseline 7-Week Follow-up (9/23/10) (11/16/10) Anterior Posterior Anterior Posterior 23 Prior therapies include: Sorafenib, an mTOR inhibitor, & Sunitinib
Slide 24: Radiographic Response in a Patient with RCC
Radiographic Response in a Patient with RCC Baseline 8-Week Follow-up Prior therapies include: mTOR inhibitor, Sunitinib, & Gemcitabine 24
Slide 25: Conclusions-Cabozantinib (XL 184)
Conclusions-Cabozantinib (XL 184) • Known spectrum of kinase activity (IC50 < 20nM) VEGFR2, MET, KIT, RET, AXL, Tie2, FLT3 • Known spectrum of clinical activity Profound effect on bone-tumor compartment Regression of soft tissue disease • Known single agent adverse event profile in CRPC Most
Slide 26: Unanswered Questions and Future Directions
Unanswered Questions and Future Directions • What is mechanism of activity? • What is optimal dose and schedule? • Clinical development in CRPC Single agent approach • Pain and bone scan resolution • Overall survival • Delay in development of bone metastases Combination with abiraterone • Possib
Slide 27: Cabozantinib mCRPC Data Update
Cabozantinib mCRPC Data Update Matthew Smith, MD, PhD Massachusetts General Hospital Cancer Center
Slide 28: Phase 2 Study of Cabozantinib in CRPC with Measurable Soft Tissue Disease
Phase 2 Study of Cabozantinib (XL184) in a Cohort of Patients With Castration-Resistant Prostate Cancer (CRPC) and Measurable Soft Tissue Disease David C. Smith1, Matthew R. Smith2, Eric J. Small3, Christopher J. Sweeney4, Razelle Kurzrock5, Michael S. Gordon6, Nicholas J. Vogelzang7, Christian Sche
Slide 29: Role for MET and VEGFR in Tumor-Bone Interactions in CRPC
Role for MET and VEGFR in Tumor-Bone Interactions in CRPC • Bone metastases are the major cause of morbidity in CRPC and are associated with high levels of MET expression • Osteoblasts and osteoclasts express MET and VEGFRs, and respond to HGF and VEGF • HGF and VEGF may be important factors directi
Slide 30: Methods
METHODS Study Design • The CRPC cohort is investigated as part of a Phase 2 randomized discontinuation trial • Patients received cabozantinib at 100 mg qd over a 12-week Lead-In Stage • Treatment allocation after week 12 was based on response: − patients with PR → open-label cabozantinib, − patients
Slide 31: Results
RESULTS This is an analysis of preliminary data from a fully enrolled study Definition of Populations Analyzed • Enrolled: patients enrolled as of January 27, 2011 (N = 168) • Primary end point evaluable: patients with at least 12 weeks of follow-up (n = 100) • Bone scan response evaluable: patients
Slide 32: Baseline Characteristics (n = 100)
Baseline Characteristics (n = 100) Age, years Median (range) 68 (47–88) ≥ 65, n 69 ECOG performance status, % 0 54 1 46 PSA (ng/mL), median (range) 54 (2–1327) tALPa (U/L), median (range) 108 (39-2283) Hemoglobin (g/dL), median (range) 12.5 (9–15) Prior lines of therapy, % 0 45 1 49 >1 6 Prior docet
Slide 33: Patient Disposition
Patient Disposition Summary of Treatment Status in the Lead-In Stage, n 100 Completed Lead-In Stagea,% 74 Treatment discontinuation ≤ week 12, (%) 26 Primary reason for discontinuation, % Progressive disease 10 Adverse event 9 Otherb 5 Death 1 Lost to follow-up 1 aWeek 12 overall response of PR or S
Slide 34: Frequently Reported Adverse Events During Lead-In Stage
Frequently Reported Adverse Events During Lead-In Stage Regardless of Causality (n = 100) Adverse Eventa All Grades, % Grade ≥ 3, % Fatigueb 71 15 Decreased appetite 52 2 Diarrhea 46 1 Nausea 40 2 Constipation 34 — Dysphonia 33 — Vomiting 29 2 • No related Grade 5 events Hypertensionb 25 8 reported
Slide 35: Summary of Effects on Bone Scan
Summary of Effects on Bone Scana Bone scan evaluableb, n 62 Complete or partial resolution, n (%) 53 (85) Stable, n (%) 8 (13) Progressive disease, n (%) 1 (2) aBest time point evaluation of changes in areas of radiotracer uptake attributable to metastatic disease per independent radiologist review.
Slide 36: Summary of Effects on Bone Pain per Investigator
Summary of Effects on Bone Pain per Investigatora Bone metastases and bone pain at baselineb, n 43 Pain improvement at week 6 or 12, n (%) 26 (60) Narcotic medication for bone pain at baselinec, n 33 Pain improvement at week 6 or 12, n (%) 21 (64) Decrease or discontinuation of narcoticsd, n (%) 13
Slide 37: Examples of Patients with Complete or Partial Bone Scan Resolution
Examples of Patients with Complete or Partial Bone Scan Resolutiona Baseline Week 6 Baseline Week 6 Baseline Week 6 Baseline Week 6 Baseline Week 6 Bone scans at baseline and during therapy with cabozantinib Prior yes yes yes No No Docetaxel Maximum tumor -14 -26% -17% -28% -12% change, per mRECIST
Slide 38: Single Patient with Bone Scan Progression as a Best Response
Single Patient with Bone Scan Progression as a Best Responsea Baseline Week 6 Prior Docetaxel No Maximum tumor change, per -5% mRECIST Improvement in bone painb Yes Change in tALP and PSA Bone scans at baseline and during therapy with cabozantinib N/A, not available; NE, not evaluated due to no pain
Slide 39: Effects on Markers of Osteoblast and Osteoclast Activity
Effects on Markers of Osteoblast (tALP) and Osteoclast (CTx) Activity A. Maximum tALP in Patients B. Maximum CTx Change in C. Median Changes in tALP and With Elevated Levels at Patients With Known Bone Plasma CTx Levels Over Time in Baseline and Known Bone Metastases (n = 48) Patients With Known Bon
Slide 40: Changes in Hemoglobin Levels Over Time in Patients with Anemia
Changes in Hemoglobin Levels Over Time in Patients with Anemia (Hb <11 g/dL) • The median maximum rise in Hb was 2.2 g/dL (range, 0.6-3.5) 40
Slide 41: Summary of mRECIST Response in the Lead-In Stage
Summary of mRECIST Response in the Lead-In Stage RECIST response evaluablea, n 100 Best objective response rate, % Confirmed responseb 6 Stable diseasec 82 Progressive disease 4 12 week DCRd, n (%) 74 a Enrolled ≥ 12 weeks prior to data cutoff ; post-baseline overall assessments not performed for 8
Slide 42: Kaplan-Meier Plots of Investigator-Assessed Progression-Free Survival
Kaplan-Meier Plots of Investigator-Assessed Progression-Free Survival (PFS) PFS from Day 1 PFS from Week 12 Randomization • Median PFS not yet reached for • Median PFS for cabozantinib arm not yet either group reached • Censoring rates: docetaxel-naïve • Median PFS for placebo is 40 days (95% 85%; d
Slide 43: Best Time Point Response in Target Lesions
Best Time Point Response in Target Lesions for Patients With ≥ 1 Post-Baseline Tumor Assessment (n = 91) % Change from Baseline ********* Docetaxel-naïve Prior docetaxel 0% change from baseline 43
Slide 44: Effects of Cabozantinib on PSA and Tumor Measurements at Week 6
Effects of Cabozantinib Treatment on PSA and Tumor Measurements at Week 6 (n = 88) Changes in PSA independent of: • Reduction or stability of tumor target lesions • Resolution of bone lesions on bone scans • Changes in bone pain 44
Slide 45: Summary
SUMMARY Cabozantinib (Cabo) shows encouraging clinical activity in both bone and soft tissue metastatic lesions in CRPC patients • Overall disease control rate at week 12 of 74% • Bone scan resolution (complete or partial) in 53 of 62 (85%) or stabilization in 8 of 62 patients (13%) associated with:
Slide 46: Cabozantinib Development Plan
Cabozantinib Development Plan Ron Weitzman, MD Vice President, Clinical Development Howard Scher, MD Memorial Sloan-Kettering Cancer Center
Slide 47: Phase 3 Regulatory Strategy & Development Plan: General Approach
Phase 3 Regulatory Strategy & Development Plan: Outline of General Approach Phase 3 to leverage the unique attributes of cabozantinib • Dual effect on both metastatic soft tissue and bone lesions • Resolution of symptomatic bone pain reported by patients/PI’s Address key CRPC populations underserved
Slide 48: Phase 3 Trials Aim to Follow Signals in Phase 2
Phase 3 Trials Aim to Follow Signals in Phase 2 Phase 3 Phase 2 Signal Study Population Primary Endpoints Pain Relief Painful Bone Mets Study 1: Composite Endpoint Pain & Bone Scan mCRPC patients with bone mets Study 2: Resolution of lesions Overall Survival on bone scan Pre-metastatic CRPC Study 3:
Slide 49: Optimal Dose Selection in CRPC
Optimal Dose Selection in CRPC RDT starting dose 100 mg (free base) across 9 different tumor types 100 mg dose represents the upper bound of a range of active doses Lower doses are clearly active: Bone responses, disease/pain control maintained on lower doses Lower doses result in benefit post c
Slide 50: Ongoing and Planned Trials of Cabozantinib in CRPC
Ongoing and Planned Trials of Cabozantinib in CRPC 2010 2011 2012 & beyond ASCO-GU mCRPC RDT ASCO Annual Meeting chemo treated Potential Subpart H Filing Non-Randomized Extension Inform Composite Endpoint Phase 3 Composite Endpoint mCRPC Lifecycle management Phase 3 Survival Combination Studies pre-
Slide 51: The Response to an FDA Challenge to Develop New Prostate Cancer Trial Metrics
The Response to an FDA Challenge To Develop New Prostate Cancer Trial Metrics: ODAC 3/5/2005 1. Traditional measures of “response” of limited value 2. Objectives: Response: Control, relieve, eliminate: PAIN Time to event: Survival 3. Less reliance on PSA; traditional response measures of limited val
Slide 52: Survival vs Pain Endpoint in mCRPC Phase 3 Studies
Survival vs Pain Endpoint in mCRPC Phase 3 Studies Approval based on overall survival endpoint Generally offers a much broader label Survival studies are large, and require longer follow-up Outcome prone to effects of active post-study salvage therapies No agent with OS label has a pain labe
Slide 53: History of Relevant Regulatory Approvals in mCRPC
History of Relevant Regulatory Approvals in mCRPC Agent 1º Endpoint Sample Size Pain Label? Approval Docetaxel vs Survival 1006 No Full Mitoxantrone/P Cabazitaxel vs Survival 755 No Full Mitoxantrone/P Mitoxantrone Pain vs 161 Yes Full Response Prednisone Samarium Week-4 Pain Study A:118 vs Yes Full
Slide 54: Survival vs Pain Endpoint in mCRPC P3 Studies
Survival vs Pain Endpoint in mCRPC P3 Studies Primary composite endpoint: pain palliation + bone scan response Definition of “pure” pain response is widely accepted/validated A novel definition of bone scan response has been developed Composite endpoint strengthens the design of the study Redu
Slide 55: Overview of Phase 3 Study 306 (Composite Endpoint)
Overview of Phase 3 Study 306 (Composite Endpoint) Composite of pain and bone scan response with additional endpoints Duration of pain and bone scan responses SREs, PFS, OS Effects on Hgb and bone markers Validated method of pain assessment and collection Brief Pain Inventory, 11 point numer
Slide 56: Lessons Learned From (Failed) Satraplatin Submission
Lessons Learned From (Failed) Satraplatin Submission 56
Slide 57: Wrap Up and Q&A
Wrap Up and Q&A
Slide 58: Exelixis Investor Update
Exelixis Investor Update ASCO GU Symposium February 17, 2011