Dendreon.Final

Samia TharaSarah MerlenMatthieu Boulenger

1

HISTORY

1992

Dr Edgar Engleman

Dr Samuel Strobber

Biotechnology company called:Activated Cell Therapy

Moutain View, California

•First activity : isolating hematopoietic stem cells from blood for use in patients with cancer who require transplantation.

2

After several years : Activated Cell Therapy

• Activity shift : developing therapeutic products that fight cancer by manipulating aspects of the immune system

• Today:

o CEO : Mitchell H. Gold

o 650 employees (April 2010)

o Main Manufacturing facility in Morris Plain (NJ)

Seattle, Washington state

3

« Targeting Cancer, Transforming Lives »

HISTORY

4

FUNDING

•DENDREON came public in 2000 (NASDAQ) : $10 per share

•Major shareholders:

o Mutual Fund : Fidelity Growth Company Fund: 9.50% of shares held

o Individual Investors : David L Urdal (Executive vice president of Dendreon): 0.36% of shares held

February 13, 2011: $35.15

DENDREON is focused on the discovery, development and commercialization:

• of novel therapeutics

• that may significantly improve cancer treatment options for patients

Philosophy of Dendreon : produce Active Cellular Immunotherapy products

stimulate an immune response against a variety of tumor types

5

ACTIVITY

CANCER THERAPIES

• Cancer is characterized by abnormal cells that grow and proliferate,

• forming masses called tumors

• Cancer therapies must eliminate or control

•BUT : may not have the desired therapeutic effect may result in significant detrimental side effects

the growth of the cancer

Chemotherapy

RadiationSurgeryHormone treatments

New approach to Cancer Treatment:

IMMUNOTHERAPIES 6

Active Cell Immunotherapy« Activates the body 's ability to fight cancer »

7

8

RESEARCH ACTIVITY

•First step : to find antigens expressed on cancer cells that are suitable targets for cancer therapy

Internal antigen discovery program

License agreements

9

Second step: to engineer antigens designed to stimulate and maximize cell-mediated immunity

Creation of the “Antigen Delivery Cassette™”

Aim : to raise the quality and the quantity of the immune response

= The key to robuste immune response

RESEARCH ACTIVITY

10

FIRST TARGET

PROSTATE CANCER

In the mid-90’s

•Estimated new cases and death in 2010 (US) :

New cases: 217,730

Deaths: 32,050

The second most common type of cancer among men in the USA

ESTIMATED NEW CASES

PROSTATE

11

Diagnosis Symptoms Stages •Average age when diagnosed:70 years

•Physical examination

• Dosing Prostate Specific Antigen

•Biopsy => Gleason score

•Often asymptomatic at the beginning

•Pain

•Difficulty in urinating

•Problems during sexual intercourse

•Erectile dysfunction

• Such as Benign Prostatic Hyperplasia

•Low growth

•Hormono-dependant

•Hormono-independant after one to three years and resume growth despite hormone therapy.

PROSTATE CANCER

12

PROVENGE®: Active Cell Immunotherapy applied to

Prostate Cancer 3 actors:

Recombinant antigen: composed of

Prostatic Acid Phosphatase (expressed in more than 95% of prostate cancers cells) GM-CSF : Granulocyte-macrophage colony-stimulating factor

Antigen Presenting Cell: white blood cells removed from the patient through LEUKAPHERESIS

T-Cells: actived by the APC-PAP-GM-CSF, attack the tumor cells

13

1

PRODUCTION & DELIVERY

14

LEUKAPHERESIS

•In a cell collection center

•Antigen Presenting Cells are removed

•Rest of the blood is returned to the patient

15

3 to 4 hours

2


16

MANUFACTURING

• Incubation of Antigen-Presenting-Cell & Prostatic Antigen

17

40 hours

APC-PAP-GM-CSF=

Sipuleucel-T (PROVENGE®)

www.provenge.com

3


18

PATIENT INJECTION• Injection of Provenge® = APC-PAP-GMCSF • 3 days after Leukapheresis

19

20

Cost of 1 injection: $ 31,000Total cost of the treatment : $

93,000

SCHEME OF INJECTIONS

21

A HUGE LOGISTIC

Dendreon website

22

Provenge’s indication : treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate

cancer

Provenge®

PROVENGE MARKET

23

PROVENGE MARKET

PROVENGE SALES

Total in 2010 : $48 M

• About only 500 patients were treated in 2010 (in 8 months)

• Expectations (2009) : to treat 8% of the Asymptomatic Metastatic AIPC market7300 patients

we can expect a large progression

24

25

What’s next for PROVENGE in the USA?

Expectations in 2014:•Market shares = 35%

•Patients treated= 38,628

BUT can DENDREON provide enough Provenge® to meet

demand?

•Enough Recombinant Prostatic Antigen?

•Enough Infusions Centers?

•Enough Manufacturing capacity?

2011: A YEAR OF GROWTH

Supply of the recombinant Antigen

• DENDREON doesn’t produce the antigen itself

• The company utilizes third party suppliers to manufacture and package the recombinant antigene

• First collaboration :

• Since September 2010 , second supplier :

26

MANUFACTURING FACILITIES

Los Angeles

Mid 2011

• New-Jersey : additional capacity expected in march 2011

• Atlanta & LA: additional capacity starting in mid-201127

PROPERTY & EQUIPMENT

28

76 235

127 427

1730

12 285

INFUSIONS CENTERS

Increase of number of Infusion centers by 9 fold in 2011for DENDREON to be near their patients 29

OTHER ISSUES FOR 2011

30

SALES FORCES

• Increase of the sales forces to approximatly 100 reps to service 450 centers by the end of 2011

Significant increase in outreach to maximize the additional capacity

REIMBURSEMENT

• Will CMS recommend and provide national reimbursement?•Date of national decision : March, 30,2011 •But some local Medicare contractors already reimburse PROVENGE®

Good clue for a positive decision by CMS

JP Morgan – Dencreon MEDCAC All Bark & No Bite; Panel Backs Provenge

31

Trade name Type of treatment Company Phase

PROSTVAC® Viral vector Bavarian Nordic Phase II completed

GVAX GM-CSF gene-transfected cell vaccines

BioSante Pharmaceuticals

Phase III

DCVAX Prostate Cellular vaccine Northwest Biotherapeutics

Phase III

TROVAX® Viral vector Oxford Biomedical Phase III

IPILIMUMAB Monoclonal antibodies BMS Phase III

ABIRATERONE Hormonotherapy Janssen-Cilag Phase III

EMERGING COMPETITORS FOR PROSTATE CANCER

32

PIPELINE

Extension of Indication: Androgen Dependent Prostate Cancer (phase 3 : awaiting data on overall survival)

Potential Raise of the market for PROVENGE®

Dendreon website

Active Cell Imunotherapy

New Antigen targets?

HER2/neu

CA-9

CEA

33

PIPELINE


HER2/neu

CA-9

CEA

34

PIPELINE


HER2/neu

= Human Epidermal Growth Factor Receptor 2

Membrane Glycoprotein involved in cell growth and differenciation Composed of:

• an extracellular domain for binding ligands

• a single transmembrane segment

• an intracellular domain carrying tyrosine-kinase activity

35

BREAST CANCER and HER/neu

Total : 207,090

The HER2 protein is overexpressed in about 30% of all breast cancers

(USA)Total : 207,090

36www.cancer.gov

One drug already targetting HER2 : Trastuzumab HERCEPTIN®

Recombinant humanised IgG1 monoclonal antibody

37

BREAST CANCER and HER/neu

Opportunities in different solid tumors expressing HER2/neu

• Breast

• Ovarian

• Colorectal

• Bladder

Initiate Phase 2 trial 1Q 2011

Lapuleucel-T NEUVENGE®Lapuleucel-T NEUVENGE®38

HER2/neu

39

BLADDER CANCER & HER2/neu

Bladder cancer : 70,530 new cases in 2010 (USA)

The 4th most frequent cancer in men

HER2 expression in bladder cancer : very variable between the different studies (from 9 to 81%)

WHY TO CONDUCT A CLINICAL TRIAL IN BLADDER CANCER AND NOT IN BREAST CANCER?

WHY TO CONDUCT A CLINICAL TRIAL IN BLADDER CANCER AND NOT IN BREAST CANCER?

HER2 Cancer market : HERCEPTIN® No indication in the bladder cancer

Neuvenge® targeting HER2 in breast cancer : Vs

HERCEPTIN?

Neuvenge® targeting HER2 in bladder cancer : Vs

placebo?

PIPELINE



HER2/neu

CA-9

CEA

40

CA-9

•In-licensed from Bayer Corporation, Business Group Diagnostics

= Carbonic Anhydrase IX

•Transmembrane protein involved in cell proliferation

the only tumor-associated carbonic anhydrase isoenzyme known

Tumors over-expressing CA-9:•Colon

•Cervical

•Kidney

41

CA-9 is overexpressed in 75% of Renal cell Carcinoma

phase 1 in Renal Cell Carcinoma planned in 2011

PIPELINE



HER2/neu

CA-9

CEA

42

CEA

• In-licensed from Bayer Corporation, Business Group Diagnostics

=CarcinoEmbryonic Antigen : glycoprotein involved in cell adhesion

• Not usually present in healthy adults, although levels are raised in heavy smokers

Cancers expressing CEA :

• Breast (65%)

• Lung (70%)

• Colon

Phase 1 expected in 2012

43

Activ

e Ce

llula

r Im

mun

othe

rapi

es Market

Phase 3

Phase 2

Pre-clinical

44

PIPELINE

DIFFICULTIES FOR ACI PRODUCTS DEVELOPMENT

45

Activ

e Ce

llula

r Im

mun

othe

rapi

esSm

all M

olec

ule

Market

Phase 3

Phase 2

Pre-clinical

46

TRPM8

=Transient Receptor Potential Cation Channel subfamily M member 8

• transmembrane cation channel identified through Dendreon’s internal antigen discovery program

Patent on the gene in 2001

Over-expressed in :

• 100% of prostate cancers• 71% of breast cancers• 93% of colon cancers• 80% of lung cancers

Synthesis of small molecule agonists

Attractive target

47

Activation by agonist induces Ca++ to flow into cells

APOPTOSIS

TRPM8: Mechanism of Action

•The small molecule agonist is orally available

Clinical phase 1 trial ongoing

48

49

AND NOW…CONQUEST OF THE WORLD ?

JUST A BEGINNING

50

WHO’S NEXT?

World age-standardised rates (per 100,000 males) for prostate cancer in 2008 51

DENDREON’S FIRST TARGET

52

EUROPE « Europe is our first ex-US opportunity »

•Market for metastatic AIPC patients = 1.5X to 2X US

•Overall market characteristics similar to US

Both urologists & oncologists are involved in treatment Treatment paradigms similar Significant therapeutic unmet need remains

•DENDREON CEO Mitch Gold :

« Low rates of PSA testing in Europe meant that many men arrived in their physicians office with metastatic disease »

JP Morgan Conference call – January 2011

53

DIFFERENT STRATEGIES TO EXPAND OUTSIDE THE USA

OR

2 Strategies:

Licensing

To go alone ?

WHAT ABOUT LICENSING?

1998: license agreement : rights for PROVENGE in Asia and

Pacific countries

2003 : released its rights for

PROVENGE 54

55

LICENSING?

Advantages

• Greater local knowlege of the Regulatory agencies by the licensee.

• Better manufacturing capacity of the licensee

• No administrative expenses and no cost of good solds for Dendreon (PROVENGE® commercialization needs much money)

Disadvantage

•DENDREON will depend on the skills, abilities and ressources of

the licensee as a source of revenue dependence

DENDREON’S CHOICE : to go alone in EUROPE

Why this choice?•2 hypothesis:

Own will of DENDREON

They want 100% of worldwide rights

They don’t want to share their revenues

Choice by default: they didn’t find any partners?

•Too risky? No certitude to get an european approval

Reimbursement?

Provenge « is not just a pill in a bottle »

Corporate image of growth

56

TRIALS

D9902IMPACT D9901

MONEY

Provenge

Senior Notes

WHAT DO THEY NEED?

TRIALS & REGULATORY

58

IMPACT TRIAL

•Randomized•Double-blind•Multicenter

•512 men•With asymptomatic •Or minimally symptomatic MPC

•Primary endpoint :Overall survival•Secondary endpoint:•Time to objective disease progression

VS Placebo 59

Dendreon website

PRIMARY ENDPOINT

Survival median : 4.1 months

60Dendreon website

IMPACT TRIAL: NEGATIVE POINTS?

IMPACT TRIAL

Primary endpoint: Overall survival

trials done versus placebo: ethic problems, same efficiency

versus taxotere?

patients having metastases: what medicine did they take before? (docetaxel approval for prostate cancer by FDA: 19/05/2004)

ethnic population isn’t the same and ethny change impact of the

disease

Secondary endpoint: Time to objective disease survival

FDA agreed to allow Dendreon to amend the design of the IMPACT study

61

REIMBURSEMENT CHALLENGE

Market access and reimbursement success is key to realizing full product potential in E.U.

Key factors influencing reimbursment:

• overall survival is the « gold standart » for payers

IMPACT: 4 months survival benefits against placebo…

• total cost of care is taken into account

$93,000/ complete cost treatement for Provenge VS $18,000/ 6 cycles of treatment for taxotere

lack of required premedication and supportive care costs compared to Taxotere

62

63

WHERE TO HAVE A PLACE?

• Find a strategic place in EUROPE

wich must be:

Near airport and road network

In a reasonable distance from each European capital

Able to cover the majority of the market

• DENDREON’s decision to build its manufacturing site: GERMANY

50% of patients live in less than 8 hours to this site in car or flight

JP Morgan Conference call – January 2011

64

• During DENDREON submits an European authorization (late 2011/early 2012)

Initial manufacturing through a Contract Manufacturing Organization (CMO):

Qualifying a CMO can be done faster than plant construction

Dendreon expects to save 12 to 18 months by outsourcing to support filing.

• Concurrently DENDREON will build its first manufacturing site:

Initiate built out in 2011

Huge expenses!!

WHERE TO HAVE A PLACE?

65

WITH WICH MONEY?

Revenues from Provenge : $48 millions in 2010

January, 14th 2011: Dendreon announced the pricing of a publing offering of $540 million convertible senior notes

Raise the equity : in the beginning of 2010 : public offering of 15 Million shares

66

CONCLUSION

67

Strengths Weaknesses

Opportunities Threats

- ACI : revolutionary therapeutic approach

- ACI : less AEs than chemotherapy

- One drug on the market at least : Provenge revenues

- Huge logistic : difficult to copy for generics

- Huge logistic : ExpensiveRestrictions for

Clinical trials

- Provenge sales too low compared to expectations

- Increase of debts (senior notes)

- No profit yet

- Expansion In the USA In Europe : similarity

with US market

-Provenge : new indication in development

- ACI : repeatible with new Antigens other cancers targeted

-Decision for reimbursment of Provenge expected in March

- Emerging competitors

- At the mercy of the EMA for the approval of Provenge (clinical trial vs. Taxotere?)

EXPECTATIONS

68

69

HIRING OPPORTUNITIES

Regulatory affairs

Quality assuranceManufacturin

g

Logistic coordinators

Sales & Marketing

R & D

70

WOULD WE JOIN DENDREON?

Transition from a total R&D to a fully-integrated commercial company

Cancer treatment is a « noble » domain

Working for a revolutionary process as ACI must be exciting

Development of domains corresponding to our professional expectations

Regulatory Challenge in Europe

New jobs in Regulatory Affairs

Development of new ACI products

Evaluation of new markets

71

YES!

WOULD WE JOIN DENDREON?

72FOR YOUR ATTENTION

73

BACK UP

Hormone-refractory metastatic prostate cancer

Reference Treatment: Docetaxel (Taxotere®) + prednisone/prednisolone

Cost-effectiveness evaluation, Sanofi-Aventis,2005:

Median survival (from Kaplan Meyer) •Taxotere+prednisone: 18.9 months •Vs mitoxantrone+prednisone : 16.5 months

Total per patient cost:•Taxotere+prednisone: £15.767(including first-line chemotherapy and for further therapy)

Adverses events :•Fatigue•Nausea, vomiting,diarrhea•Alopecia•Sensory neuropathy

R Collins,1* E Fenwick,2 R Trowman,1 R Perard,2 G Norman,1 K Light,1 A Birtle,3 S Palmer2 and R Riemsma1

74

Clinicaly localized disease

Biochemical Reccurence

Castration-Resistant Disease

Castration-Resistant Disease

Metastatic

Primary Therapy(Surgery,Radiation

therapy…)

Hormonal Therapy (chemical

castration)

Secondary Hormonal Therapy

Docetaxel+ chemotherapy

immunotherapy

TREATMENTS

75

2006

March 2007

April 2009

Initial clinical results showed immune response

April 2010

Building a manufactory facility in New Jersey to accommodate production for a

phase III trial

FDA accepted Dendreon’s BLA filling for Provenge®

FDA voted 17-0 that Provenge is reasonably safe and that the trial data showed substantial evidence that it is

effective

Dendreon received a letter from the FDA demanding more results and information

before approval

Dendreon announced that the results for the Phase III trial of Provenge were

positive

FDA approved Provenge for use in the treatment of advanced prostate cancer.

DISCOVERY OF PROVENGE®

76

CANCER IMMUNOTHERAPIES CAN BE EITHER :

PASSIVE OR ACTIVE

•immunomodulators, antibodies or immune cells

•to initiate an anti-tumor action

•not targeted to a specific antigen

•Use in : breast cancer, melanoma, renal cell carcinoma, leukemia...

•Stimulates the patient's immune system

•using the body's own immune cells

•generates a T-cell response against tumor-associated antigens

a type of therapeutic cancer vaccine •Ex: adoptive T-cell therapy

77

CA-9

•In-licensed from Bayer Corporation, Business Group Diagnostics

= Carbonic Anhydrase IX

•Transmembrane protein involved in cell proliferation

the only tumor-associated carbonic anhydrase isoenzyme known

Tumors over-expressing CA-9:•Colon

•Cervical

•Kidney

78

CA-9 is overexpressed in 75% of Renal cell Carcinoma

phase 1/2 in Renal Cell Carcinoma planned in 2011

KIDNEY CANCER and CA-9

TREATMENTS :•Surgery, •Often resistant to chemotherapy and radiotherapy•Well responder to immunotherapy

Total : 46,592

79

KIDNEY CANCER and CA-9

•Good opportunity for Dendreon’s Active Cell Immunotherapy;

•First pre-clinical results presented at the American Association of Immnology:

Candidate product targeted at CA-9 significantly prolonged survival in animal tumor models

phase 1/2 in Renal Cell Carcinoma planned in 2011

80

Dendreon.Final

Documents

Transcript of Dendreon.Final