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


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


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


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



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


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


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


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


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


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


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


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


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


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)


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


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


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



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



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)



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


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)



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



XL184 Shows Promising Activity in Previously Treated NSCLC Patients

Best Radiologic Time Point Response of Patients with >1 Post-baseline Tumor Assessment



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)



Melanoma Cohort: Tumor Shrinkage Observed Regardless of BRAF Status



XL184 Resulted in a High Rate of Disease Stabilization in Melanoma

Time on Study Treatment Regardless of Treatment

Assignment Post-Week 12



Hepatoma Cohort: Effects on Tumor and AFP

Response rate per RECIST: 19%



Hepatoma Cohort: XL184 Results in Prolonged Disease Control, Regardless of Prior Sorafenib Therapy



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


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


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


Typical Outcome Following Docetaxel

Baseline Month 5 Month 8

PSA 14.6tALP 344

4.3240

15.3325


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


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


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)



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



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



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


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


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)



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



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


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


Cook et al (2006) Clin Cancer Res

NTx BAP

Overall Survival by Quartiles of NTx and BAP


XL184 Effects on Markers of Bone Remodeling Occur Regardless of Prior Zoledronic Acid Therapy

Osteoblast Activity (bone formation) Osteoclast Activity (bone resorption)



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


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


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


CRPC Panel - Leaders in the Field of Prostate Cancer

Instrumental role in the development of:• Cabazitaxel

• Sipuleucel-T

• Abiraterone

• MDV3100

• Denosumab

XL184 Development Strategy and Commercial Overview

Gisela Schwab, EVP, CMORon Weitzman, VPGautam Kollu, VP


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


Strategy for Multiple Potential XL184 Marketing Approvals

MULTIPLE GLOBAL REGULATORY FILINGS ANTICIPATEDSTARTING WITH MTC IN 2011

Broad Opportunity:Anti-Tumor & Bone Effect


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


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


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


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


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


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


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


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


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


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


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


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


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


Stepwise Approach to Commercialization

MTC<100 prescribers

mCRPC3,000-5,000 prescribers

Other solid tumors5,000-10,000 prescribers

Staged, Incremental Commercial Investments


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


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


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


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


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


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


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


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


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


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


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

Annual R&D DayDecember 2, 2010

analyst day 2010l

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