Download - analyst day 2010l
Annual R&D DayDecember 2, 2010
2 Annual R&D Day - December 2, 2010
Forward-Looking Statements
This presentation contains certain statements that are forward-looking, including, without limitation, statements relating to Exelixis’ plan to focus on XL184, the continued development and clinical, therapeutic and commercial potential of XL184, future development opportunities and priorities for XL184, Exelixis’ plan to aggressively manage expenses, the potential strategic monetization of XL184, Exelixis’ belief that XL184 is the main value driver for the company, Exelixis’ plan to maximize the value of XL184, future XL184 data presentations, including ASCO GU and ASCO, Exelixis’ belief that there is significant opportunity for XL184 in metastatic castration-resistant prostate cancer (CRPC) and plan to prioritize development of XL184 in CRPC, the expected read-out for the ongoing phase 3 trial for medullary thyroid cancer (MTC) in the first half of 2011 and plan to file a new drug application in MTC in the second half of 2011, Exelixis’ belief that the next data sets from the XL184 randomized discontinuation trial (RDT) will drive the next stage of development for XL184, key XL184 milestones in the first half of 2011 and Exelixis’ belief that such milestones will drive news flow, Exelixis’ plan to reduce its operating expense and extend its runway, Exelixis’ plan to restructure the company to focus resources on XL184, potential non-dilutive financing opportunities, Exelixis’ belief that the RDT trial design may have the effect of underestimating the efficacy signal of XL184, the potential for XL184 to have utility in a broad spectrum of common cancers, the strategy and potential pathways for XL184 marketing and other regulatory approvals, the pursuit of a novel composite endpoint for CRPC for purposes of potential regulatory approval and potential advantages related thereto, lifecycle planning for XL184 in CRPC, potential approaches and opportunities with respect to the commercialization of XL184, the objective of rapidly achieving profit center status, Exelixis’ 2010 year-end balance with respect to cash and cash equivalents, marketable securities, long-term investments and restricted cash and investments, Exelixis’ 2011 financial outlook, including expected P&L improvements, planned expense reductions and anticipated cash inflows, the potential future receipt of milestones and other payments under Exelixis’ collaborative arrangements, the expected impact of the restructuring announced today on Exelixis’ business and the development of XL184, estimated reductions in personnel and cash expenditures as a result of the restructuring, estimated restructuring charges and the timing thereof, Exelixis’ belief that 2011 could potentially be a breakout year for the company. Words such as “potential,” “opportunities,” “expect,” “driving,” “updates,” “extend,” “focus,” “encouraging,” “promising,” “may,” “will,” “plans,” “priorities,” “suggest,” “can,” “likely,” “anticipate,” “predict,” “objective,” “enables,” “maximize,” and similar expressions are intended to identify forward-looking statements. These statements are only predictions and are based upon Exelixis’ current plans, assumptions, beliefs and expectations, and are subject to risks and uncertainties. Exelixis’ actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to: the potential failure of XL184 to demonstrate safety and efficacy in clinical testing; the ability to conduct clinical trials for XL184 sufficient to achieve a positive completion; the uncertain timing and level of expenses associated with the development of XL184; the availability of data at the referenced times; Exelixis’ ability to successfully pursue and obtain non-dilutive financing; the sufficiency of Exelixis’ capital and other resources; Exelixis’ ability to implement the restructuring plan to the extent currently anticipated; timely receipt of potential reimbursements, milestones, royalties and profits under Exelixis’ collaborative agreements; the uncertainty of the FDA approval process; unanticipated changes in accounting rules; market competition and changes in economic and business conditions. These and other risk factors are discussed under “Risk Factors” in Exelixis’ Quarterly Report for the quarter ended October 1, 2010 and Exelixis’ other reports filed with the Securities and Exchange Commission. Exelixis expressly disclaims any duty, obligation or undertaking to release publicly any updates or revisions to any forward-looking statements made in this discussion to reflect any change in Exelixis’ expectations with regard thereto or any changes in events, conditions or circumstances on which any such statements are based.
Annual R&D Day - IntroductionMichael Morrissey, Ph.D.Chief Executive Officer
4 Annual R&D Day - December 2, 2010
Today’s Agenda
Exelixis Overview
Review of recent clinical data from RDT – CRPC focus
CRPC Panel Discussion
CRPC Development and Commercial Overview
Exelixis Priorities for 2011
5 Annual R&D Day - December 2, 2010
The New Exelixis - Key Themes
EXELIXIS IS THE XL184 COMPANY
• XL184 is the primary value driver• Singular focus moving forwardFocus on XL184
• Pragmatic XL184 development plan• High-value commercial opportunities
Expedite Development
• Aggressive expense management• Strategically monetize XL184Improve P&L
6 Annual R&D Day - December 2, 2010
Exelixis’ Value Driven by Success of XL184
XL184 is the primary value driver – singular focus moving forward• Differentiated profile - targets both metastatic soft-tissue and bone lesions
• Robust clinical data suggests broad commercial potential
• Objective responses in 9/12 indications with resolution of bone lesions in 4
• Planned CRPC updates at ASCO GU & ASCO – additional patients & duration
Bone metastases represent a major unmet medical need in oncology• Bone metastases occur in ~300,000 patients with cancer in the US annually
• Most common with prostate, breast & lung cancer & multiple myeloma
• Incidence rates as high as 90% of patients in some metastatic diseases
EXELIXIS IS THE XL184 COMPANY
7 Annual R&D Day - December 2, 2010
XL184 Development Priorities – Emphasis on CRPC
CRPC is a significant commercial opportunity• Differentiated XL184 profile drives overall strategy
• Short, mid and long-term development plans
MTC first potential NDA filing• Phase 3 readout expected in 1H 2011, NDA filing planned for 2H 2011
RDT will drive additional indications• Ovarian, HCC, melanoma, NSCLC, breast – consider cooperative groups
Reprioritize other efforts in select indications• Phase 3 trial for refractory GB deprioritized – will not initiate in 4Q10
2011 PRIORITIES – MTC FILING & ADVANCE CRPC TO PHASE 3
8 Annual R&D Day - December 2, 2010
Key XL184 Milestones in 1H 2011
ASCO GU – CRPC data• ~100 evaluable patients, ~50 with metastasis on bone scan
• Duration of follow-up approximately 4+ months
ASCO Annual Meeting – data updates• 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
9 Annual R&D Day - December 2, 2010
Reduce Operating Expense – Extend Runway
Aggressive management of expenses• Fund only XL184 development efforts & programs reimbursed by partners
• XL184 expenses focused on near term value drivers – CRPC, MTC, RDT
Restructure company to focus resources on XL184 • Eliminate unfunded discovery & clinical programs
• Significantly reduce personnel
• Initiate process to reduce fixed costs
Impact of March 2010 reduction in force taking hold
ALIGN RIGOROUS FINANCIAL DISCIPLINE WITH XL184 FOCUS
10 Annual R&D Day - December 2, 2010
XL184 Data Provides Opportunity for Non-Dilutive Financing
Strategically monetize XL184• Explore broad range of opportunities
• Pursue near term cash and development funding
• Expand bandwidth and regional regulatory expertise
Partner remaining preclinical & clinical compounds• Recent BMS transaction highlights value of early assets and programs
• Oncology programs – XL888, XL541, XL388, XL228, FGFR
• Inflammation – XL499, PI3Kγ, selective JAK1, others
NUMEROUS FINANCING OPPORTUNITIES AVAILABLE
11 Annual R&D Day - December 2, 2010
The New Exelixis - Key Themes
EXELIXIS IS THE XL184 COMPANY
• XL184 is the primary value driver• Singular focus moving forwardFocus on XL184
• Pragmatic XL184 development plan• High-value commercial opportunities
Expedite Development
• Aggressive expense management• Strategically monetize XL184Improve P&L
12 Annual R&D Day - December 2, 2010
Oncology Experts Participating in EXEL R&D Day
Jose Baselga, MD, PhDChief of the Division of Hematology / Oncology Associate Director of Massachusetts General Hospital Cancer Center
Philip Kantoff, MDChief, Division of Solid Tumor Oncology, Chief Clinical Research Officer Director Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute
Oliver Sartor, MDMedical Director of Tulane Cancer Center; C.E. and Bernadine Laborde Professor of Cancer Research; Professor, Department of Medicine: Section of Hematology & Medical Oncology and Department of Urology
Howard Scher, MDChief of Genitourinary Oncology Service at the Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan-Kettering Cancer Center
Matthew Smith, MD, PhDDirector of the Genitourinary Malignancies Program Massachusetts General Hospital Cancer Center
Dr. Jose BaselgaChief of the Division of Hematology / Oncology Associate Director of Massachusetts General Hospital Cancer Center
14 Annual R&D Day - December 2, 2010
XL184 Target Profile
ATP competitive, reversible
RTK Cellular IC50 (nM) Autophosphorylation
MET 8VEGFR2 4
Kinase IC50 (nM)
MET 1.8
VEGFR2 0.035
RET 5.2
KIT 4.6
AXL 7.0
TIE2 14
FLT3 14
S/T Ks (47) >200
15 Annual R&D Day - December 2, 2010
Upregulation of MET as a Response to Treatment
EGFR Inhibition
Androgen Receptor Blockade
VEGF Pathway Inhibition
Hypoxia, HIF1 stabilizationUp-regulation of MET
Selection for MET amplification(NSCLC)
Relief of AR-mediated repression (Prostate)
MET Expression
16 Annual R&D Day - December 2, 2010
RIP-TAG2 model - highly vascularized pancreatic neuroendocrine tumors• Initial response to VEGF inhibition is tumor stasis, followed by regrowth of invasive and
metastatic tumors• No relapse seen on XL184 – tumors are non-invasive and don’t metastasize
Preclinical Differentiation: XL184 vs Selective VEGF Pathway Inhibition
Lack of invasive tumor cells after administration of XL184
Elimination of liver metastasesafter administration of XL184
17 Annual R&D Day - December 2, 2010
Clinical Summary
XL184 is showing broad clinical activity in various solid tumors in a randomized discontinuation trial• Castration-resistant prostate cancer
• Ovarian cancer
• Breast cancer
• Hepatocellular cancer
• Non-small Cell Lung Cancer
• Melanoma
XL184 profile appears to be highly differentiated• XL184 has simultaneous effects on soft tissue and bone metastases
Dual targeting of MET and VEGFR2 with XL184 may have broad utility for the treatment of cancer• MET inhibition by XL184 may prevent development of escape resistance from
VEGFR targeting
18 Annual R&D Day - December 2, 2010
Randomized Discontinuation Study Design
Tumor Types
Breast cancer
Gastric/GEJ cancer HCC Melanoma NSCLC Ovarian
cancerPancreatic
cancerProstate cancer SCLC
XL184 given orally qd at 100 mg (125 mg salt equivalent)
19 Annual R&D Day - December 2, 2010
Advantages and Disadvantages of the RDT Design Used
Advantages• Rapid simultaneous readout of multiple efficacy signals
• Single clinical trial “umbrella”
• Explores the meaning of stable disease
Disadvantages• Skews population towards measurable disease
• Has the effect of selecting for a harder to treat population
• Results in treatment interruption in ~50% of patients with stable disease
RDT DESIGN CAN UNDERESTIMATE EFFICACY SIGNAL
20 Annual R&D Day - December 2, 2010
Broad Anti-tumor Activity Across Multiple Tumor Types
Effects in bone
(N = 269)
39 PARTIAL RESPONSES IN 269 PATIENTS WITH ≥ 1 POST-BASELINE ASSESSMENT
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
21 Annual R&D Day - December 2, 2010
XL184 Achieved High Rates of Disease Control Across a Variety of Tumor Types
Tumor CohortNumber Enrolled
PRa
(N)
Response Evaluable
(N)
Week 12SDb
N (%)
PRb,c
N (%)
DCRd
(%)HCC 29 3 cPR 16 9 (56) 3 (19) 75Prostate 99 3 cPR, 2 uPR 34 19 (56) 5 (15) 71Ovarian 51 10 cPR, 4 uPR 31 9 (29) 11 (35) 64Melanoma 77 2 cPR, 2 uPR 58 23 (40) 3 (5) 45Breast 20 2 cPR, 2 uPR 19 4 (21) 4 (21) 42NSCLC 59 5 cPR, 3 uPR 55 16 (29) 7 (13) 42SCLC 21 1 uPR 21 7 (33) 1 (5) 38Pancreatic 20 0 20 7 (35) 0 35Gastric/GEJ 21 0 19 6 (32) 0 32Total 397 39 273 100 (37) 34 (12) 49a Partial response (PR) includes unconfirmed PRs (uPR) and confirmed PRs (cPR) at any time pointb Denominator = Response Evaluablec PR = cPR + uPRd Disease Control Rate (DCR) = (PR + SD) at Week 12 / Response Evaluable
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
22 Annual R&D Day - December 2, 2010
XL184 Effects Observed in Both Soft Tissue and Bone
Decreases in circulating markers of both osteoclast and osteoblast activity
cTX changes in pts with knownbone metastases (N = 52)CTx Bone Alkaline
Phosphatase
Osteoclasts OsteoblastsBone formationBone destruction
Baseline BaselineWk 6 Wk 12
BONE SCAN RESOLUTION IN BOTH PROSTATE AND BREAST CANCERPATIENTS WITH BONE METASTASES
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
23 Annual R&D Day - December 2, 2010
All Patients Treated with XL184: Most Frequent Adverse Events in Lead in Stage, Regardless of CausalityAdverse Event All Grades, n (%) Grade ≥ 3, n (%)Fatigue 200 (64) 34 (11)Diarrhea 152 (49) 16 (5)Nausea 138 (44) 8 (3)Decreased appetite 126 (40) 6 (2)Vomiting 89 (29) 9 (3)Constipation 87 (28) 4 (1)PPE Syndromea 73 (23) 24 (8)Dysgeusia 68 (22) –Hypertension 67 (21) 16 (5)Rash 67 (21) 7 (2)Dysphonia 64 (21) –Abdominal pain 62 (20) 13 (4)Transaminases increased 55 (18) 8 (3)Stomatitis 48 (15) 3 (1)Hemorrhage 47 (15) 8 (3)Rare medically important eventsThrombosis venous 17 (5) 12 (4)Thrombosis arterial 4 (1) 4 (1)aPPE, palmar-plantar erythrodysesthesia
Four related Grade 5 events were reported: pulmonary embolism (melanoma); respiratory failure (breast cancer), hemorrhage (NSCLC), GI-hemorrhage (pancreatic cancer)
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
24 Annual R&D Day - December 2, 2010
XL184 Activity in Ovarian Carcinoma Appears Independent of Platinum Status
Overall population 32% PRPlatinum resistant/refractory disease 29% PRPlatinum sensitive disease 40% PR
Duration of response ranging up to 36+ weeksInterim RDT data presented at 2010 EORTC-NCI-AACR Symposium
25 Annual R&D Day - December 2, 2010
Breast Cohort: XL184 Achieved Tumor Shrinkage in the Majority of Patients
Patient Histology Receptor Status
Site of Target Lesions
Number of Prior Treatments
Most Recent Prior Treatment (Best Response)
Time on XL184 (weeks)
1 Invasive lobular
ER+/PR–/ HER2+ lymph node 3 fulvestrant (UNK) 25+
2 Invasive ductal
ER+/PR+/ HER2 (ND) liver 2 paclitaxel (UNK) 18+
3 Invasive ductal
ER+/PR–/ HER2–
lung and lymph nodes 3 exemestane/bosutinib (SD) 18+
4 Invasive ductal
ER+/PR+/ HER2 (ND) chest wall 3 carboplatin/gemcitabine (UNK) 17
ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor; ND, not determined SD, stable disease; UNK, unknown
Best Radiological Time Point Response in Patients with ≥ 1 Post-Baseline Tumor Assessment (N = 16)
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
26 Annual R&D Day - December 2, 2010
Breast Cohort: Effects in Soft Tissue & Bone Metastases
Bone scan resolution in patient with invasive ductal carcinoma; Concurrent 29% reduction of a tumor lesion and a 82% reduction in plasma CTx levels.
Prior anticancer treatment: radiotherapy, paclitaxel/adriamycin, hormonal therapy, ixabepilone
Response in chest wall lesion in a patient with invasive ductal carcinoma
Prior anticancer treatment: 5-FU/epirubicin/cyclophosphamide, docetaxel, gemcitabine/carboplatin
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
27 Annual R&D Day - December 2, 2010
XL184 Shows Promising Activity in Previously Treated NSCLC Patients
Best Radiologic Time Point Response of Patients with >1 Post-baseline Tumor Assessment
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
28 Annual R&D Day - December 2, 2010
NSCLC: Dramatic Response in Tumor with XL184
Radiographic Images from a 72-Year-Old Male with Metastatic NSCLC
Radiographic Images from a 88-Year-Old Female with Metastatic NSCLC
PATIENT WITH ADENOCARCINOMA WITH A 61% REDUCTION IN THE SUM OF TARGET LESIONS
PRIOR ANTICANCER TREATMENT: SUNITINIB(SD AS BEST RESPONSE)
PATIENT WITH ADENOCARCINOMA WITH A 36% REDUCTION IN THE SUM OF TARGET LESIONS
PRIOR ANTICANCER TREATMENT: PACLITAXEL/CARBOPLATIN, ERLOTINIB, INVESTIGATIONAL AGENT (SD AS BESTRESPONSE)
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
29 Annual R&D Day - December 2, 2010
Melanoma Cohort: Tumor Shrinkage Observed Regardless of BRAF Status
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
30 Annual R&D Day - December 2, 2010
XL184 Resulted in a High Rate of Disease Stabilization in Melanoma
Time on Study Treatment Regardless of Treatment
Assignment Post-Week 12
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
31 Annual R&D Day - December 2, 2010
Hepatoma Cohort: Effects on Tumor and AFP
Response rate per RECIST: 19%
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
32 Annual R&D Day - December 2, 2010
Hepatoma Cohort: XL184 Results in Prolonged Disease Control, Regardless of Prior Sorafenib Therapy
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
33 Annual R&D Day - December 2, 2010
Non-CRPC Indications: Conclusions
XL184 demonstrates broad clinical activity across multiple tumor types:
• 39 PRs in 269 pts with ≥ 1 post-baseline assessment
• Promising activity in ovarian cancer, breast cancer, NSCLC, HCC, and melanoma
• CRPC data discussed by Dr. Matthew Smith
Evidence of activity in sites of both visceral and bone metastases
Simultaneous targeting of both MET and VEGFR may have utility in a broad spectrum of common cancers
Dr. Matthew SmithProgram Director, Genitourinary OncologyMassachusetts General Hospital
35 Annual R&D Day - December 2, 2010
Précis
Bone metastases are the dominant cause of prostate cancer morbidity and mortality
Effective therapies for castration-resistant disease are an important unmet medical need
• Chemotherapy modestly improves survival but has little impact on bone disease
• Bone-targeted therapy reduces skeletal morbidity but does not impact cancer progression
There is strong preclinical rationale for dual inhibition of MET and VEGFR in prostate cancer
Early results of XL184 in prostate cancer suggest unprecedented activity particularly in bone metastases
36 Annual R&D Day - December 2, 2010
Metastatic Prostate Cancer
Bone predominant metastases• Distinct pattern of complications
• Osteoblastic > osteolytic appearance
• High bone turnover
Following progression on ADT (mCRPC),median survival is less than 2 years
Pain, higher tALP, and lower hemoglobin are associated with shorter survival
37 Annual R&D Day - December 2, 2010
Typical Outcome Following Docetaxel
Baseline Month 5 Month 8
PSA 14.6tALP 344
4.3240
15.3325
38 Annual R&D Day - December 2, 2010
Role of MET in Prostate Cancer and Bone Metastases
Androgen deprivation activates MET signaling
HGF(autocrine+paracrine)
AR MET AR MET
Stromal HGF
Androgen Deprivation X
Zhang, et al., Mol Cancer, 2010
Activated MET is highly expressed in bone metastases
39 Annual R&D Day - December 2, 2010
MET and VEGFR in Tumor-Bone Interactions
MET is activated in bone metastases• Tumor cells express MET • Autocine and paracine activation of
MET by HGF • VEGF activation of MET via neuropilin-1
Osteoblasts and osteoclasts• Express MET and VEGFRs• Respond to HGF and VEGF• May induce growth and invasion via
production of HGF and VEGF
40 Annual R&D Day - December 2, 2010
CRPC Cohort: Baseline Characteristics
Age, years Median (range) 64 (51-83)≥ 65 25 (51)
ECOG performance status, n (%)
0 24 (49)1 25 (51)
PSA (ng/mL), median (range) 44 (2-1327)tALP (U/L), median (range) 116 (50-2283)Hemoglobin (g/dL), median (range) 12.4 (9.0-15.1)
Prior lines of therapy, n (%)0 20 (41)1 27 (55)> 1 2 (4)
Prior docetaxel, n (%) 28 (57)Measurable disease, n (%) 49 (100)Disease sites, n (%)Visceral tissue 22 (45)Lymph node 43 (88)Bone and soft tissue 34 (69)
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
41 Annual R&D Day - December 2, 2010
Tumor Shrinkage Occurred in Most CRPC Patients
Best Radiological Time Point Response in Patients with ≥ 1 Post-Baseline Tumor Assessment (N = 55)
TUMOR SHRINKAGE IN WATERFALL REPRESENTS SOFT TISSUE RESPONSES
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
42 Annual R&D Day - December 2, 2010
PSA Measurements Do Not Correlate With Anti-Tumor Effect and Pain Relief at Week 6
Effects of XL184 Treatment on PSA and Tumor Measurements at Week 6 (N=52)Tu
mor
Mea
sure
men
t
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
43 Annual R&D Day - December 2, 2010
TKIs and PSA Response
PSA response (PSA decline>50%) has often been used as a marker of efficacy in prostate cancer trials
• Based on experience with anti-androgens and chemotherapy
• Generally good correlation between PSA declines and tumor response
PSA expression is driven by AR signaling, but AR-independent regulators of expression have also been described
• Cytokines (IL-6) and soluble factors released by osteoblasts regulate PSA in complex ways
Accumulating evidence suggests that PSA response is not an appropriate measure of anti-tumor activity for TKIs
• Lack of correlation between PSA changes and tumor responses
• Different mechanism of action
44 Annual R&D Day - December 2, 2010
TKIs and PSA Response
Clinical data with TKIs in prostate cancer show disconnects between PSA and imaging responses
• Phase 2 trials with sorafenib, sunitinib and cediranib show improvements in imaging despite stable or increasing PSA
− PSA declines on treatment cessation noted
− Authors suggest PSA may not be an appropriate measure of clinical benefit for this class of agents
IN VITRO TREATMENT OF PROSTATE TUMOR CELLS WITH SORAFENIB RESULTS IN AN ACUTE STIMULATION OF PSA SECRETIONSORAFENIB INCREASES PSA SECRETION DESPITE GROWTH INHIBITION
Dahut W L et al. Clin Cancer Res 2008
45 Annual R&D Day - December 2, 2010
Summary of Anti-Tumor Activity
RECIST response evaluable, N 34a
Best objective response rate, n (%)Confirmed response 3 (9)b
Stable disease 25 (74)
– Unconfirmed response 2 (6)c
Progressive disease 2 (6)
12 week DCRd, n (%) 24 (71)Bone scan evaluablee, N 20
Complete or partial resolution, n (%) 19 (95)
Stable, n (%) 1 (5)a No post-baseline tumor assessments available for 2 patientsb Confirmed responders time on study: 18, 20+ and 27+ weeks c Unconfirmed responders time on study: 15+ and 18+ weeks d Disease control rate defined as PR + SD at Week 12e Independent review using a CAD-based scoring system (MedQIA)
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
46 Annual R&D Day - December 2, 2010
Complete or Partial Bone Scan Resolution Observed Regardless of Prior Docetaxel Exposure
Not evaluated
Bone scans: Baseline and on XL184 therapy
Tumor change
Bone pain
Change in tALP and PSA
Docetaxel Pre-treated Docetaxel Naïve
-2 4 10 16 22 280
500
1000
1500
2000
tALPPSA
0
1
2
3
ScrWeeks On Study
tALP
PSA
0 5 10 15 200
200
400
600
800
1000
tALPPSA
0
100
200
300
400
500
ScrWeeks On Study
tALP
PSA
-2 2 6 10 140
250
500
750
1000
0
250
500
750
tALPPSA
ScrWeeks On Study
tALP
PSA
-2 2 6 10 140
500
1000
1500
2000
0
500
1000
1500
2000
tALPPSA
ScrWeeks On Study
tALP
PSA
0 10 20 30 40 500
250
500
750
1000
0
20
40
60
tALPPSA
ScrWeeks On Study
tALP
PSA
-2 0 2 4 60
250
500
750
1000
0
20
40
60
80
tALPPSA
ScrWeeks On Study
tALP
PSA
-69% -41% -13% -35%
Improvement Improvement ImprovementNot evaluated Improvement
-2.5% No change
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
47 Annual R&D Day - December 2, 2010
Durable Effects Observed on Bone Scan
Bone scan resolution and cPR in a Docetaxel-pretreated CRPC patient
Baseline Week 6 Week 12 Week 18 Week 24Target lesions –43% –51% –67% –69%tALP (U/L): 661 1109 264 144a 136b
a tALP value at Week 21; b tALP value at Week 27 Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
48 Annual R&D Day - December 2, 2010
Markers of Osteoblast (BAP) and Osteoclast (NTx) Activity in Men with Metastatic Prostate Cancer
NTx (nmol/mmol creatinine)
BAP
(U/L
)
Correlation coefficient = 0.67
Normal
Cook et al (2006) Clin Cancer Res
49 Annual R&D Day - December 2, 2010
Cook et al (2006) Clin Cancer Res
NTx BAP
Overall Survival by Quartiles of NTx and BAP
50 Annual R&D Day - December 2, 2010
XL184 Effects on Markers of Bone Remodeling Occur Regardless of Prior Zoledronic Acid Therapy
Osteoblast Activity (bone formation) Osteoclast Activity (bone resorption)
Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
51 Annual R&D Day - December 2, 2010
XL184 Novel Pattern of Activity with Potential to Address Major Unmet Needs in mCRPC
Rapid improvement in bone scans
Rapid improvement in bone pain
Decrease in size of measurable soft tissue disease
Decrease in markers of both osteoclast and osteoblast activity
Increase in hemoglobin
52 Annual R&D Day - December 2, 2010
Summary – CRPC
Bone metastases are a major cause of prostate cancer morbidity and mortality
Effective therapies for mCRPC are an important unmet medical need
XL184 results suggest novel and differentiated activity profile that has the potential to address critical unmet medical needs
Thought Leader CRPC Panel Discussion
54 Annual R&D Day - December 2, 2010
Oncology Experts Participating in R&D Day
Philip Kantoff, MDChief, Division of Solid Tumor Oncology, Chief Clinical Research Officer Director Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute
Oliver Sartor, MDMedical Director of Tulane Cancer Center; C.E. and Bernadine Laborde Professor of Cancer Research; Professor, Department of Medicine: Section of Hematology & Medical Oncology and Department of Urology
Howard Scher, MDChief of Genitourinary Oncology Service at the Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan-Kettering Cancer Center
Matthew Smith, MD, PhDDirector of the Genitourinary Malignancies Program Massachusetts General Hospital Cancer Center
55 Annual R&D Day - December 2, 2010
CRPC Panel - Leaders in the Field of Prostate Cancer
Instrumental role in the development of:• Cabazitaxel
• Sipuleucel-T
• Abiraterone
• MDV3100
• Denosumab
Break
XL184 Development Strategy and Commercial Overview
Gisela Schwab, EVP, CMORon Weitzman, VPGautam Kollu, VP
58 Annual R&D Day - December 2, 2010
XL184 Development Priorities
Signal Strength Indication 2011 Plans Priority
DifferentiatedSignal
CRPCMTC
Ph 2 Expansion & Ph 3 InitiationNDA Filing High
Promising Signal
BreastGlioblastoma
HepatomaMelanoma
NSCLCOvarian
RCC
ContinuedInvestigation Medium
Modest SignalGastricSCLC
PancreasHold & Follow Low
59 Annual R&D Day - December 2, 2010
Strategy for Multiple Potential XL184 Marketing Approvals
MULTIPLE GLOBAL REGULATORY FILINGS ANTICIPATEDSTARTING WITH MTC IN 2011
Broad Opportunity:Anti-Tumor & Bone Effect
60 Annual R&D Day - December 2, 2010
XL184 Shows Encouraging Activity in Ovarian Cancer
High rate of RECIST response*• Responses occurred independent of platinum sensitivity
• Durable responses
• Response has been associated with other parameters of benefit
• e.g. improvement in ascites
• Rate of response compares favorably to other single agent therapies
Amendment for Ongoing Phase 2 Study in ovarian cancer• Convert RDT design to non-randomized single arm cohort
• Sample size = 150
• Population will have exhausted all approved therapy (unmet need)
• 100% will be platinum resistant or refractory
• 100% will have failed either liposomal doxorubicin or topotecan*Interim RDT data presented at 2010 EORTC-NCI-AACR Symposium
Castration-Resistant Prostate Cancer
62 Annual R&D Day - December 2, 2010
XL184 has an Unprecedented Spectrum of Clinical Activity
High rate of bone scan resolution associated with:• Tumor shrinkage and/or lack of progression
• Pain relief and/or reduction in narcotic use
• Impact on markers of bone formation and resorption
• Improvements in hemoglobin and hematocrit
DUAL EFFECTS ON SOFT TISSUE AND BONE METASTASES ARE DISTINCT FROM THOSE OF ANY OTHER AGENT
63 Annual R&D Day - December 2, 2010
Typical Strategies for Approval in Oncology
Full approval with demonstration of OS improvement• Large phase 3 studies with prolonged follow-up
• Cabazitaxel in CRPC
Full approval without need for OS improvement• Demonstration of direct evidence for clinical benefit in phase 3 trial
• Lenalidomide in MDS (transfusion sparing)• Mitoxantrone in CRPC (pain improvement)
Accelerated approval: single arm trial• Population: unmet medical need• Endpoint: reasonably likely to predict clinical benefit• Confirmatory phase 3 trial underway
• Bevacizumab in GBM, nilotinib in CML
XL184 DEVELOPMENT PLAN ADDRESSES ALL APPROVAL STRATEGIES
64 Annual R&D Day - December 2, 2010
pre-mCRPC
Development Overview of XL184 in CRPC
2010 2011 2012 and beyond
Phase 3 Met-Free Survival
mCRPCchemo treated
mCRPC
Non-Randomized Extension
RDT
Phase 3 Composite Endpoint
Lifecycle management
Dose Range Finding
Phase 3 Survival
Combination Studies
65 Annual R&D Day - December 2, 2010
Amendment to CRPC Cohort: RDT Converted to Non-Randomized Cohort
Current trial design likely underestimates efficacy signal• Skewed population: 100% of patients had measurable soft tissue disease
• Patients with SD by RECIST could be randomized to placebo at week 12
• i.e. patients with pain relief and complete bone scan resolution but <30% tumor shrinkage have been randomized to placebo
Amended study: Non-randomized Phase 2 cohort• Removed requirement for measurable disease
• More closely approximates the typical patient population
• Removed week 12 randomization
• Uninterrupted treatment
66 Annual R&D Day - December 2, 2010
Overview of Amendment for Ongoing Phase 2 Study
Amendment submitted to leading centers in the U.S. and U.K.• Convert RDT design to non-randomized single arm cohort in a new cohort• Sample size = 150• Population will have exhausted all approved therapy in CRPC
• Docetaxel in all, docetaxel + cabazitaxel in a substantial fraction• Introduce instruments to measure pain and analgesia use• Independent, blinded radiologic confirmation of response
Correlate “bone scan response” with:• PFS/OS• Tumor response• Pain relief and reduced use of narcotic analgesics• Rate of skeletal related events
67 Annual R&D Day - December 2, 2010
Pursue Novel Endpoint in Initial Phase 3 for Demonstration of Clinical Benefit
POTENTIAL ADVANTAGES
• Highly differentiated
• High PTS for phase 3
• Smaller sample size
COMPOSITE MEASURE OF CLINICAL BENEFIT
•Pain relief, reduction in narcotic use
•Lack of progression in other sites of disease
•Reduced skeletal morbidity
DATA FROM NON-RANDOMIZED COHORT WILL HELP TO DEFINE PRECISE NATURE OF COMPOSITE ENDPOINT, POPULATION AND COMPARATOR
68 Annual R&D Day - December 2, 2010
Life Cycle Planning: Full Potential for XL184 in CRPC
Metastatic CRPC• Demonstration of survival benefit
• XL184 vs. standard of care in metastatic CRPC pts with bone metastases
• Dual activity in both tumor and bone - unique advantage over existing SOC
• Magnitude of Ph2 signal determines population, sample size and comparator
Pre-metastatic CRPC• Demonstration of improvement in metastasis-free survival
• XL184 vs. standard of care in pre-metastatic CRPC patients
• Bone scan resolution in advanced setting may translate into prevention up front
• Requires a lower dose that retains bone activity administered over many years
• Substantial signal in bone may obviate need for very large sample size
69 Annual R&D Day - December 2, 2010
pre-mCRPC
Development Overview of XL184 in CRPC
2010 2011 2012 and beyond
Phase 3 Met-Free Survival
mCRPCchemo treated
mCRPC
Non-Randomized Extension
RDT
Phase 3 Composite Endpoint
Lifecycle management
Dose Range Finding
Phase 3 Survival
Combination Studies
70 Annual R&D Day - December 2, 2010
14.0
34.6
5.0
55.8
2.0
0
10
20
30
40
50
60
pre-mCRPC asymptomatic mCRPC (sipuleucel-T)
symptomatic mCRPC (docetaxel)
chemo-treated mCRPC (cabazitazel, abiraterone)
Patie
nts
(tho
usan
ds)
U.S. Drug Treated Incidence (2009)
1.0
0.7
Substantial Opportunity in Multiple CRPC Segments
Patients with Bone Metastases
Patients without Bone Metastases
AsymptomaticmCRPC
(Sipuleucel-T)
SymptomaticmCRPC
(Docetaxel)
Chemo-treatedmCRPC
(Cabazitaxel, abiraterone)
Source: Decision Resources
71 Annual R&D Day - December 2, 2010
XL184 Opportunity in CRPC
71
Significant opportunity for differentiated therapy
Enables multiple Ph3 trials in different CRPC segments
across lifecycle
Activity in both bone and soft tissue metastases
Baseline Week 12
Commercial OverviewGautam Kollu, VP
73 Annual R&D Day - December 2, 2010
Significant Opportunity in Bone Metastases Across Many Tumor Types
Source: Synovate Tandem Cancer Monitor
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Multiple Myeloma
Prostate HR+ Breast Thyroid RCC NSCLC Bladder Melanoma Ovarian
Perc
ent o
f Pat
ient
s
Patients with Bone Metastases
Patients without Bone Metastases
74 Annual R&D Day - December 2, 2010
Focusing on Most Promising Opportunities
NSCLC
HR+ BreastRCC
CRPC
GB
Ovarian
LowShort
High
LongLength of Survival
Com
petit
ive
Diff
eren
tiatio
n
>$1B Potential in U.S. Revenues
Sources: Decision Resources, Citeline TrialTrove
Melanoma
HCC
MTC
75 Annual R&D Day - December 2, 2010
Stepwise Approach to Commercialization
MTC<100 prescribers
mCRPC3,000-5,000 prescribers
Other solid tumors5,000-10,000 prescribers
Staged, Incremental Commercial Investments
76 Annual R&D Day - December 2, 2010
Stepwise Approach to Commercialization
MTC<100 prescribers
mCRPC3,000-5,000 prescribers
Other solid tumors5,000-10,000 prescribers
Staged, Incremental Commercial Investments
Small
Moderate
Standard
Infrastructure
77 Annual R&D Day - December 2, 2010
Building a Right Sized Commercial Structure
Web-based tacticsEfficient Retain Key
ComponentsScalableAdapted to
size of market
Effective
Objective: rapidly achieve profit center status
Optimize marketing mix for XL184’s opportunities
• Key source of information
• Targeted approach
• Social media
• Evolved org would meet key customer needs – KOLs, HCPs, payers, patients, GPOs
• Investments scaled to # of relevant customers
• Attain substantial share of voice
78 Annual R&D Day - December 2, 2010
Opportunity for Exelixis to Commercialize First Drug
Significant promise• First in class MET / VEGFR inhibitor
• Activity across multiple tumor types
• >$1B potential in U.S. revenues
Mid-stage efficacy results gaining momentum• Demonstrated differentiation
• Extensive data generated; more emerging
• MTC Ph3 data expected in 2011
Commercial planning and implementation under way• Core team build-out complete
• MTC launch planning ongoing
Corporate OverviewMichael Morrissey, CEOFrank Karbe, CFO
80 Annual R&D Day - December 2, 2010
The New Exelixis - Key Themes
EXELIXIS IS THE XL184 COMPANY
• XL184 is the primary value driver• Singular focus moving forwardFocus on XL184
• Pragmatic XL184 development plan• High-value commercial opportunities
Expedite Development
• Aggressive expense management• Strategically monetize XL184Improve P&L
81 Annual R&D Day - December 2, 2010
2010 – Transformative Year for Exelixis
Turmoil of 1H 2010 was the catalyst for change in 2H 2010• 40% RIF; regaining rights to XL184, CEO departure
Compelling XL184 clinical data repositions compound & company• New clinical data addresses prior questions about XL184
Exelixis business model refined to maximize success• Singular focus on XL184 with CRPC as the highest priority indication
Aggressively manage P&L• Commitment to financial discipline while advancing XL184
EXELIXIS VALUE DRIVEN BY SUCCESS OF XL184
82 Annual R&D Day - December 2, 2010
Restructure Exelixis to Maximize Success with XL184
• Maximize ability to advance XL184
Realign Around XL184
• All non-XL184 proprietary spend halted
Focus Proprietary Spend • Fulfill all
current collaboration commitments
Continue Current Partnerships
• Align with smaller, leaner organization
Reduce G&A Operations
ENABLES EXELIXIS TO ACCELERATE XL184 DEVELOPMENT
83 Annual R&D Day - December 2, 2010
Restructure Exelixis to Maximize Success with XL184
• Reduce headcount by ~40% by year-end• Significant reduction from current 400 employees
Additional ~65% FTE reduction over two years
• Further reductions as collaborations end in 2011/12
Exelixis resources focus exclusively on XL184
• Fewer employees in discovery, development & G&A
Headcount reductions across entire company
MAXIMIZE ABILITY TO ADVANCE XL184 & BUILD SHAREHOLDER VALUE
84 Annual R&D Day - December 2, 2010
2010 Financial Highlights
Substantially reduced Net Loss despite restructuring charges• Increased revenue due to new partnerships
• Cut back number of programs funded by Exelixis
• Reduced headcount by >40% from YE 2009 to 3Q 2010
Obtained substantial cash inflows from existing & new partnerships• ~$90 million in R&D funding and milestones
• $60 million in upfront payments related to new deals with BMS
Raised $160 million in new debt
Repaid ~$40 million in debt to GSK (in cash)
EXPECT TO END 2010 WITH APPROXIMATELY $250MN IN CASH*
*Includes cash and cash equivalents, marketable securities, long-term investments and restricted cash and investments
85 Annual R&D Day - December 2, 2010
2011 Financial Outlook
Further P&L improvements expected
Additional expense reduction planned• Exelixis funded activities focused exclusively on XL184
• XL184 efforts focused on most value added activities
• Further significant OPEX reductions and consolidation of real estate footprint
Significant cash inflows anticipated
• R&D funding (mainly PI3K related) and milestones
• Strategically monetize XL184
86 Annual R&D Day - December 2, 2010
MilestonesPre - Dev. Cost Economic Particpation (Non POS-Adj)
Compound Clinical Ph 1 Ph 2 Ph 3 Partner Share U.S. Ex-U.S. $ in MM
ProprietaryXL184 – 100% –XL228 – 100% –XL888 – 100% –XL388 – 100% –XL541 – 100% –XL499 – 100% –
PartneredXL147 / XL765 Sanofi-Aventis 0% $745XL880 GSK 0% 139XL518 Genentech 0% 30-50% Profit Share Royalty 0XL281 BMS 0% 465XL139 BMS 0% 260XL652 / XL041 (LXR) BMS 0% 363XL550 (MR) Daiichi-Sankyo 0% 136XL475 (TGR5) BMS 0% 400Notch Genentech 0% 39S1P1 Agonist BI 0% 339Pi3K Discovery Sanofi-Aventis 0% 405ROR Antagonists 0% 405
Total (14 Partnered Compounds) $3,696
100% Ownership
Global Royalty
Global Royalty
Economic Participation in Current Pipeline
87 Annual R&D Day - December 2, 2010
14%
40%
46%
Development Regulatory Commercial
Milestone Breakdown
Milestone Breakdown
$3.7 Billion
Milestones are not POS adjusted.
Substantial future milestones embedded in EXEL pipeline
• Total potential milestones of up to approximately $3.7 billion
• Milestones are in addition to royalties and profit shares
Significant source of potential medium term funding
• Numerous development related milestones potentially triggered within 1-3 years
88 Annual R&D Day - December 2, 2010
2011 – Potential Breakout Year for Exelixis
XL184 is the single focus for Exelixis moving forward• Differentiated profile - targets both metastatic soft tissue and bone lesions
CRPC is the main development and commercial priority• Best indication to invest capital - optimal risk/reward profile
First potential NDA filing in MTC• Niche indication provides foundation to initiate commercial activities
Aggressively manage expenses & strategically monetize XL184• Commitment to extend financial runway
• Numerous opportunities for non-dilutive financing
THANK YOU TO SHAREHOLDERS, ANALYSTS & EMPLOYEES
Q & A
Annual R&D DayDecember 2, 2010