Prostate Cancer Epidemiology: Estimated 2010 Total Active Disease: 773,000 Stages I-III: 508,000 Metastatic (M+): 183,000 Asymptomatic M+ CRPC Symptomatic M+ CRPC Castrate Sensitive*: 80,000 US Census, SEER 2007, NODB- IMPAC Market Research Castrate Resistant*: 103,000 *Estimated based on physician reported percentages among 200 community oncologists and urologists.(2005).

Life After Traditional Androgen Deprivation Failure Other Hormonal Therapy Chemo Therapy Immunotherapy

Rationale For Immunotherapy CancerCancer Cellular dysfunctionCellular dysfunction Resistance to or escape from host defensesResistance to or escape from host defenses Active immunotherapyActive immunotherapy Suitable target antigenSuitable target antigen Effective presentation of antigenEffective presentation of antigen Mobilization of immune cascadeMobilization of immune cascade

Antigen Presenting Cells (APCs)  Dendritic cells (DCs) are antigen-presenting cells that process and present MHC-peptide complexes to activate a T-lymphocyte response

Dendritic cell TCR MHC class I MHC class II CD8 CD4 CD80 CD86 CD28 CD54 CD11/CD18 Peptide CD154 CD40 T-cell CTLA4

sipuleucel-T (Provenge ® ) sipuleucel-T is an autologous active cellular immunotherapy that activates the immune system against prostate cancer

Sipuleucel-T: Patient-Specific Therapy Day 1 Leukapheresis Day 2-3 sipuleucel-T is manufactured Day 3-4 Patient is infused Apheresis Center DendreonDoctor’s Office COMPLETE COURSE OF THERAPY: Weeks 0, 2, 4

Primary Endpoint (Trial 9901) Time to Disease Progression Study 1 Percent without ProgressionWeeks

Secondary Endpoint - Survival Clinically Significant and Statistically Persuasive Overall Survival Benefit 34% 11% Median benefit 4.5 months

Vote of FDA Expert Panel 17 – 0 for safety 17 – 0 for safety 13 – 4 for substantial evidence of efficacy 13 – 4 for substantial evidence of efficacy FDA Requires More Data (<2% Event) FDA Requires More Data (<2% Event)

Randomized Phase 3 IMPACT Trial (IMmunotherapy Prostate AdenoCarcinoma Treatment) Primary endpoint:Overall Survival Secondary endpoint: Time to Objective Disease Progression Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer (N=512) Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer (N=512) Placebo Q 2 weeks x 3 Sipuleucel-T Q 2 weeks x 3 PROGRESSIONPROGRESSION PROGRESSIONPROGRESSION 2:1 SURVIVALSURVIVAL SURVIVALSURVIVAL Treated at Physician discretion and/or Salvage Protocol Treated at Physician discretion

Eligibility Criteria Metastatic castrate resistant prostate cancer Life expectancy of at least 6 months Serum PSA ≥ 5.0 ng/mL Castrate level of testosterone (< 50 ng/dL) achieved via medical or surgical castration Adequate hematologic, renal, and liver function Negative serology for HIV 1 & 2, HTLV-1, and Hepatitis B & C

Patient Demographics and Baseline Characteristics Sipuleucel-T (N = 341) Placebo (N = 171) Age, median yrs (range) 72 (49 – 91)70 (40 – 89) Race, white (%) ECOG status, 0 (%) Gleason Score ≤ 7 (%)75.4 Disease localization Bone only (%) Soft tissue only (%) Bone & soft tissue (%) >10 bone mets (%) Bisphosphonate use Prior docetaxel (%)

Baseline Median Laboratory Values Sipuleucel-T (N = 341) Placebo (N = 171) Serum PSA, ng/mL Serum PAP, U/L Alk. Phosphatase, U/L Hemoglobin, g/dL LDH, U/L WBC, 10 3 /µL

IMPACT Overall Survival: Primary Endpoint Intent-to-Treat Population P = (Cox model) HR = [95% CI: 0.614, 0.979] Median Survival Benefit = 4.1 Mos.

Overall Survival Summary Survival Percentiles (months) N75%50%25% Sipuleucel-T Placebo mos % Survival (K-M estimates 24 Mos.36 Mos.48 Mos. Sipuleucel-T Placebo % 16.0

Survival Consistency Between Population Subsets

Survival Results Confirmed by Multiple Sensitivity Analyses

Most Common Adverse Events (≥ 5%) Higher Rate in Sipuleucel-T (p ≤ 0.05) Preferred Term Sipuleucel-T N = 338 % Placebo N = 168 % Chills Pyrexia Headache Influenza-like illness Hypertension Hyperhidrosis5.30.6

Serious Adverse Events* Safety Population Serious Adverse Events* Safety Population SAE Preferred Term Sipuleucel-T N=338 % Placebo N=168 % Any SAE Pyrexia Cerebrovascular accident1.8 Pulmonary embolism Spinal cord compression1.2 Nausea Atrial fibrillation Dehydration Cardiac failure congestive Pneumonia Hematuria Deep vein thrombosis Renal failure acute *Occurring in ≥ 4 patients.

Consistency Across Phase 3 Studies D9901* (N = 127) D9902A* (N = 98) IMPACT ** (N = 512) Hazard Ratio p-value p = p = p = Median Survival Benefit (months) Month survival (%) sipuleucel-T placebo 34% 11% 32% 21% 32% 23% *Unadjusted Cox model & log rank **Cox model adjusted for PSA and LDH Integrated** (N=737) p < % 20%

SummarySummary First active immunotherapy to demonstrate improvement in overall survival for cancer Highly favorable benefit to risk profile Short duration of therapy Potential to create new paradigm in treatment of metastatic, castrate resistant prostate cancer

Time to Objective Disease Progression Secondary endpoint Result –Independent radiologic review –HR=0.951 (95% CI: 0.77,1.17); P=0.628 (log rank) Consistent with other trials in advanced prostate cancer Difficult endpoint to measure reliably and doesn’t correlate with overall survival

PSA-TRICom Randomized Phase II Study Primary endpoint: Progression Free Survival Secondary endpoint: Overall Survival Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer (N=125) Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer (N=125) Empty Vector + placebo PROSTVAC-VF Tricom + GM PROGRESSIONPROGRESSION PROGRESSIONPROGRESSION 2:1 SURVIVALSURVIVAL SURVIVALSURVIVAL Treated at physician discretion and/or Salvage Protocol Treated at physician discretion

25 PSA-TRICom Progression-Free Survival

26 PSA-TRICom Overall Survival

27 Background-The Development of PROSTVAC-VF-Tricom Vaccinia –Potent immunological priming agent –Derived from wild-type Wyeth strain (used in millions of immunizations) Fowlpox –Minimally/non-cross-reactive with vaccinia  Enables boosting Slightly altered PSA transgene Tricom –Lymphocyte function-associated antigen LFA-3 (CD58) –Intercellular adhesion molecule ICAM-1 (CD54) –Costimulatory molecule for the T-cell receptor B7.1 (CD80)

28 PROSTVAC-PSA-Tricom PrimeBoosts Vaccinia-PSA-Tricom Fowlpox-PSA-Tricom

Conclusions Poxviral-based immunotherapy is feasible and safe Primary endpoint of prolonged PFS was not met Secondary endpoint of prolonged median OS –8.5 month difference in OS, HR 0.56 (95% CI ) with p= Baseline characteristics of patients in both arms similar Need to validate these findings in large Phase III study with survival endpoint