Before, Frank's immune cells could

(1)

Now, they are

focused on it.

Before,

Frank's immune cells could

(2)

The precise mechanism of action of PROVENGE is not known.

Stimulate an immune response against advanced prostate cancer

Extend median survival beyond 2 years

in men with asymptomatic or minimally symptomatic metastatic CRPC.

PROVENGE

is the first in a new class of therapy that is designed

to activate a patient’s own antigen-presenting cells (APCs) to stimulate

an immune response against prostate cancer.

INDICATION: PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of

asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

IMPORTANT SAFETY INFORMATION: PROVENGE is intended solely for autologous use and is not routinely tested

for transmissible infectious diseases.

In controlled clinical trials, serious adverse events reported in the PROVENGE group include acute infusion reactions

(occurring within 1 day of infusion) and cerebrovascular events. Severe (Grade 3) acute infusion reactions were

reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea,

hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. No Grade 4 or 5

acute infusion reactions were reported in patients in the PROVENGE group.

The most common adverse events (incidence ≥15%) reported in the PROVENGE group are chills, fatigue, fever,

back pain, nausea, joint ache, and headache.

(3)

Stimulate a Response

Making the decision to treat

PROVENGE expands your therapeutic options

➜

Prostate cancer is the second leading cause of cancer-related death in men

1

➜

In advanced prostate cancer, the disease will eventually progress in most men

on androgen deprivation therapy

2

➜

Metastatic CRPC is an aggressive disease with median survival from 15.5 months

to 21.7

3

_*

Vigilant monitoring and the resulting early diagnosis of metastatic disease

provide an opportunity to treat these patients…

…before they are symptomatic.

Early identification of progression allows you to treat patients who have:

➜

Metastatic CRPC that is asymptomatic or minimally symptomatic, defined as:

−

No moderate-to-severe prostate cancer–related pain

−

No use of narcotics for cancer-related pain

*Median survival range is based on the control group of recent clinical studies in this patient population. 1. American Cancer Society. Cancer Facts & Figures 2010. Atlanta, GA: American Cancer Society; 2010. 2. Kantoff PW, Carroll PR, D’Amico AV, eds. Prostate Cancer: Principles and Practice. Philadelphia, PA:

Lippincott Williams & Wilkins; 2002.

3. Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411-422.

Now with PROVENGE, you have another way to take action for your

asymptomatic or minimally symptomatic metastatic CRPC patients.

(4)

The precise mechanism of action of PROVENGE is not known.

1. Goldstein NS. Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. Am J Clin Pathol. 2002;117:471-477.

The active component of PROVENGE consists of a patient’s own APCs that

have been cultured with a recombinant antigen to stimulate the body’s immune

system against prostate cancer

PROVENGE—the first FDA-approved

autologous cellular immunotherapy

The precise mechanism of action of PROVENGE is not known.

PROVENGE Proposed Mechanism of Action

PAP-GM-CSF ANTIGEN COMBINES WITH RESTING APC T CELLS PROLIFERATE TO TARGET PROSTATE CANCER CELLS APC TAKES UP

THE PAP-GM-CSF PAP-GM-CSF IS PROCESSED AND PRESENTED ON THE SURFACE OF THE APC

ACTIVE

T CELL INACTIVE T CELL

PROVENGE ACTIVATES T CELLS

IN THE BODY

PAP-GM-CSF–LOADED APCs ARE NOW THE ACTIVE COMPONENT

OF PROVENGE

INFUSE PATIENT

PROSTATIC ACID PHOSPHATASE (PAP)—AN ANTIGEN

1

GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF)—AN IMMUNE-CELL ACTIVATOR EXPRESSED IN MORE THAN 95% OF PROSTATE CANCERS1

(5)

Stimulate a Response

Primary endpoint: overall survival

After independent confirmation of objective disease progression:

➜

All patients were treated at their physicians’ discretion

➜

Patients in the control group had the option to enter a Phase 2,

open-label protocol

−

Treatment—

An autologous immunotherapy made from cells

that were cryopreserved at the time of control generation

−

Participation—

63.7% of patients in the control group

entered the Phase 2 protocol

1. Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411-422.

The PROVENGE pivotal trial

The pivotal trial was a randomized, double-blind, multicenter, controlled*

Phase 3 trial of 512 patients with asymptomatic or minimally symptomatic

metastatic CRPC

➜

Primary endpoint—

Overall survival

➜

Secondary endpoint—

Time to objective disease progression

2:1

Asymptomatic

or Minimally

Symptomatic

Metastatic

CRPC

(N=512)

P

R

O

G

R

E

S

IO

N

S

U

R

V

IV

A

L

Control*

Q2 weeks x 3

PROVENGE

Q2 weeks x 3

Treated at

Physician

Discretion

Treated at

Physician Discretion

Including

Entry Into Phase 2,

Open-Label Protocol

Trial Design

1

(6)

The precise mechanism of action of PROVENGE is not known.

➜

An earlier Phase 3 trial (D9901) supports survival results: 25.9 months for

patients in the PROVENGE group compared with 21.4 months for patients

in the control group (HR=0.586 [95% CI: 0.388, 0.884] P=.010)

†

➜

Analyses of time to disease progression did not meet statistical significance

in any Phase 3 study of PROVENGE

PROVENGE extends median

survival beyond 2 years

Reporting results

Reduction in risk of death:

22.5% for patients in the PROVENGE group compared

with patients in the control group (HR=0.775 [95% CI: 0.614, 0.979] P=.032)*

Overall Survival

1,2

*Control was nonactivated, autologous, peripheral blood mononuclear cells.

†_{In Study D9901, all patients were followed for survival; however, overall survival was not a prespecified endpoint.}

1. PROVENGE [package insert]. Dendreon Corporation; April 2010.

100 75 50 25 0 0 12 24

Time From Randomization (Months)

36 48 60 72 Survival (%) PROVENGE (n=341) Control (n=171)

21.7

months

25.8

months

Reduction in risk of death: 22.5%

(95% CI: 0.614, 0.979)

P=.032

HR=0.775

Data originally published in the New England Journal of Medicine: Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411-422.

(7)

Stimulate a Response

INDICATION: PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment

of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

IMPORTANT SAFETY INFORMATION: PROVENGE is intended solely for autologous use and is not routinely

tested for transmissible infectious diseases.

In controlled clinical trials, serious adverse events reported in the PROVENGE group include acute infusion

reactions (occurring within 1 day of infusion) and cerebrovascular events. Severe (Grade 3) acute infusion

reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue,

asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and

vomiting. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group.

The most common adverse events (incidence ≥15%) reported in the PROVENGE group are

chills, fatigue, fever, back pain, nausea, joint ache, and headache.

1. Data on file. Dendreon Corporation.

Survival probabilities: 1, 2, 3, and 4 years

1

PROVENGE helps your patients continue

their fight against advanced prostate cancer

Extending survival

Kaplan-Meier Survival Rate Estimates in the Pivotal Trial

1

PROVENGE

40 30 20 10 0 Per centage Incr ease in PROVENGE Gr oup vs Contr ol Gr oup*

1 year

2 years

3 years

4 years

1 year

2 years

3 years

4 years

12.0

26.5

37.8

28.1 PROVENGE

Control

81.1 (76.9, 85.3)

n=274

31.7 (25.7, 37.8)

n=49

72.4 (65.6, 79.1)

n=123

23.0 (15.5, 30.5)

n=19

52.1 (46.4, 57.7)

n=129

41.2 (33.5, 49.9)

n=55

20.5 (14.0, 26.9)

n=14

16.0 (8.5, 23.4)

n=4

Percentage of Patients Alive: ITT Population (95% CI)

(8)

The precise mechanism of action of PROVENGE is not known.

Analyzing safety

Acute infusion reactions:

➜

Acute infusion reactions (occurring within 1 day of infusion) were reported in 71.2% of

patients in the PROVENGE group

−

In 95.1% of patients, acute infusion reactions were mild or moderate

−

The most common acute infusion reactions (≥20%) were chills, fever, and fatigue

−

Fevers (71.9%) and chills (89.0%) generally resolved within 2 days

➜

1.2% of patients in the PROVENGE group were hospitalized within 1 day of infusion

for management of acute infusion reactions

➜

No Grade 4 or 5 acute infusion reactions were reported in patients in the

PROVENGE group

For 67.4% of patients reporting adverse events in the

PROVENGE group, these events were mild or moderate.

With PROVENGE, the most common adverse

events are primarily mild or moderate

Most Common Adverse Events

1

_*

†

The most common adverse events

(≥15%) reported in the PROVENGE

group are chills, fatigue, fever,

back pain, nausea, joint ache,

and headache.

* All grades reported in ≥15% of patients randomized to PROVENGE.

†_{The safety analysis is based on 601 prostate cancer}

patients in the PROVENGE group who underwent at least 1 leukapheresis procedure in Phase 3 clinical trials.

‡ _{Control was nonactivated, autologous, peripheral blood}

mononuclear cells.

ANY GRADE

Chills

Fatigue

Fever

53.1

41.1

31.3 Back pain

Nausea

Joint ache

Headache

29.6

21.5

19.6

18.1

28.7

14.9

20.5

6.6

10.9

34.7

9.6 Control

‡ (n=303) (%)

ADVERSE EVENT

PROVENGE

(n=601) (%)

(9)

Stimulate a Response

Considering the data

Only 1.5% of patients in the pivotal trial discontinued

treatment with PROVENGE due to adverse events.

1. PROVENGE [package insert]. Dendreon Corporation; April 2010. 2. Data on file. Dendreon Corporation.

In the PROVENGE group:

➜

Grade 3 adverse events were reported

in 23.6% of patients compared with

25.1% of patients in the control group

➜

Grade 4 adverse events were reported

in 4.0% of patients compared with 3.3%

of patients in the control group

➜

Grade 5 adverse events were reported

in 3.3% of patients compared with

3.6% of patients in the control group

➜

Serious adverse events included

acute infusion reactions and

cerebrovascular events

−

Cerebrovascular events, including

hemorrhagic and ischemic strokes,

were reported in 3.5% of patients

compared with 2.6% of patients in

the control group

A demonstrated safety profile

*Reported in ≥1% of patients in the PROVENGE group.

† _{Control was nonactivated, autologous, peripheral blood}

mononuclear cells.

Grades 3–5 Adverse Events

1,2

_*

Any adverse event

Back pain

Chills

Anemia

Joint ache

Cerebrovascular

accident

Dyspnea

Spinal cord

compression

Pain

Asthenia

Fatigue

Hematuria

Fever

30.9

3.0

2.2

1.8

1.7

1.2

1.0

1.0 PROVENGE

(n=601) (%)

Control

† (n=303) (%)

ADVERSE EVENT

GRADES 3–5

32.0

3.0

0.0

2.3

1.7

2.0

1.0

0.3

1.0

0.7

1.3

1.0

(10)

The precise mechanism of action of PROVENGE is not known.

PROVENGE is indicated for men with:

➜

Metastatic CRPC

➜

Asymptomatic or minimally symptomatic disease, defined as:

−

No moderate-to-severe prostate cancer–related pain

−

No use of narcotics for cancer-related pain

Certain additional criteria from the PROVENGE pivotal trial for consideration:

➜

No visceral (lung, liver, or brain) metastases

➜

ECOG Performance Status 0 or 1

➜

No treatment with chemotherapy in at least the previous 3 months

➜

No treatment within 28 days with systemic corticosteroids

Knowing who to treat

(11)

Stimulate a Response

Expanding options for your patients

Creating a new opportunity in your

treatment of advanced prostate cancer

1. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. V.1.2011. National Comprehensive Cancer Network Web site. www.nccn.org. Accessed December 14, 2010. 2. Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T

immunotherapy for castration resistant prostate cancer. N Engl J Med. 2010;363:411-422.

PROVENGE did not preclude use of subsequent therapies.

➜

In the pivotal trial, 81.8% of patients in the PROVENGE

group received additional anticancer treatments

2

Men with less advanced disease (no or minimal symptoms)

should consider immunotherapy with PROVENGE; men who

are symptomatic should be considered for chemotherapy.

—NCCN Guidelines1

NCCN Guidelines: PROVENGE Included for Treatment of Advanced Prostate Cancer

1

M1*†

• Docetaxel • Mitoxantrone

• Palliative radiotherapy or radionuclide for symptomatic bone metastases • Clinical trial • Secondary hormone therapy • Clinical trial • Cabazitaxel • Salvage chemotherapy • Docetaxel rechallenge • Mitoxantrone

• Secondary hormone therapy • Clinical trial Progression

ADT

• Symptomatic • Visceral disease • Asymptomatic • PROVENGE® (sipuleucel-T) • Asymptomatic or minimally symptomatic with ECOG 0-1

ADT=androgen deprivation therapy. *M1=Distant metastasis.

†_{Maintain castrate serum levels}

of testosterone and use denosumab or zoledronic acid if there are bone metastases.

(12)

The precise mechanism of action of PROVENGE is not known.

PROVENGE is designed to stimulate the immune system:

➜

Concurrent use of chemotherapy or immunosuppressive agents (such as systemic

corticosteroids) may alter efficacy and/or safety

➜

Carefully evaluate patients to determine whether it is medically appropriate to reduce

or discontinue immunosuppressive agents prior to beginning treatment cycles

91.8% of patients in the PROVENGE group in the

pivotal trial received a complete course of therapy.

2

*The dosing interval ranged from 1 to 15 weeks in controlled clinical trials.

1. Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration resistant prostate cancer. N Engl J Med. 2010;363:411-422.

2. Data on file. Dendreon Corporation.

A Sample PROVENGE Schedule

Leukapheresis Procedure

Treatment can be completed in approximately 1 month

1

➜

Median time was 28 days in the pivotal trial

1

➜

PROVENGE is administered as 3 infusions, generally 2 weeks apart.* Each infusion

is preceded by a standard leukapheresis procedure

Facilitating treatment

PROVENGE—transforming therapy with

a regimen that is complete in 3 cycles

➜

Each infusion takes approximately 60 minutes. To help minimize infusion reactions such

as chills and fever, approximately 30 minutes prior to infusion with PROVENGE, pretreat

patients orally with acetaminophen and an antihistamine such as diphenhydramine

(13)

Stimulate a Response

Handling the details

Please ask your Dendreon sales representative how to

become an infusion site for PROVENGE therapy.

Or, ask how you can refer patients to a site that has

already been approved.

One call activates Dendreon ON Call

for support services throughout therapy

www.PROVENGE.com

*

Co-pay and travel assistance foundations provide assistance regardless of the choice of medicine, and decisions are based on financial need and according to criteria established by individual foundations. Dendreon can assist patients by referring them to these independent organizations. Dendreon cannot

guarantee that patients will be eligible for or receive assistance after referral. Dendreon does not have controlling or managerial influence on these independent organizations.

†_{Services vary by office based on application criteria and are subject to change or discontinuation.}

Patient Assistance

Programs

Dedicated case managers

to provide referrals to or

information on:

• Independent foundations

that may assist patients with

co-pays, co-insurance, and

deductible costs*

• Independent foundations

that may assist patients with

treatment-related travel costs*

Reimbursement

Support

Dedicated case managers to help:

• Verify benefits

• Assist with prior authorizations

• Support claims appeals

• Provide referrals to local field

personnel who can offer

assistance with reimbursement–

Product Support

Dedicated case managers who:

• Generate patient schedules and

leukapheresis reminder calls

• Ensure timely product

ordering and delivery

• Handle product spoilage

and returns

• Facilitate extended

payment terms

†

(14)

(15)

(16)

PROVENGE—the first in a new class of therapy...

INDICATION: PROVENGE

®

_{(sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment}

of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

IMPORTANT SAFETY INFORMATION: PROVENGE is intended solely for autologous use and is not routinely

tested for transmissible infectious diseases.

In controlled clinical trials, serious adverse events reported in the PROVENGE group include acute infusion

reactions (occurring within 1 day of infusion) and cerebrovascular events. Severe (Grade 3) acute infusion

reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue,

asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and

vomiting. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group.

The most common adverse events (incidence ≥15%) reported in the PROVENGE group are chills, fatigue,

fever, back pain, nausea, joint ache, and headache.

Please see enclosed full Prescribing Information for PROVENGE.

* The dosing interval ranged from 1 to 15 weeks in controlled clinical trials.

➜

Extends median survival

beyond 2 years—

25.8 months compared with

21.7 months for patients in

the control group (P=.032)

➜

Therapy completed in 3 cycles—

3 infusions, at approximately

2-week intervals*

➜

Most common adverse events

are primarily mild or moderate—

chills, fatigue, fever, back pain,

nausea, joint ache, and headache

Overall Survival

1,2

Data originally published in the New England Journal of Medicine: Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411-422. 100 75 50 25 0 0 12 24

Time From Randomization (Months)

36 48 60 72 Survival (%) _months21.7 25.8 months PROVENGE (n=341) Control (n=171)

Reduction in

risk of death:

22.5%

(95% CI: 0.614, 0.979) P=.032 HR=0.775