Dendreon

Samia TharaSarah MerlenMatthieu Boulenger

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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.

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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

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« Targeting Cancer, Transforming Lives » 

HISTORY

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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

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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 »

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RESEARCH ACTIVITY

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

Internal antigen discovery program

License agreements

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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

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FIRST TARGET

PROSTATE CANCER

In the mid-90’s

• Estimated new cases and deaths 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

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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

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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

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PRODUCTION & DELIVERY

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LEUKAPHERESIS

• In a cell collection center

• Antigen Presenting Cells are removed

• Rest of the blood is returned to the patient

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3 to 4 hours

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PRODUCTION & DELIVERY

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MANUFACTURING

• Incubation of Antigen-Presenting-Cell & Prostatic Antigen

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40 hours

APC-PAP-GM-CSF=

Sipuleucel-T (PROVENGE®)

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PRODUCTION & DELIVERY

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PATIENT INJECTION• Injection of Provenge® = APC-PAP-

GMCSF • 3 days after Leukapheresis

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

93,000

SCHEME OF INJECTIONS

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A HUGE LOGISTIC

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

cancer

Provenge®

PROVENGE MARKET

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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

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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 :

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MANUFACTURING FACILITIES

Los Angeles

Mid 2011

• New-Jersey : additional capacity expected in march 2011

• Atlanta & LA: additional capacity starting in mid-201128

PROPERTY & EQUIPMENT

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76 235

127 427

1730

12 285

INFUSIONS CENTERS

Increase of number of Infusion centers by 9 fold in 2011 for DENDREON to be near their patients 30

OTHER ISSUES FOR 2011

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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

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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

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PIPELINE

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

Potential Raise of the market for PROVENGE®

Active Cell Imunotherapy

New Antigen targets?

HER2/neu

CA-9

CEA

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PIPELINE

Active Cell Imunotherapy

HER2/neu

CA-9

CEA

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PIPELINE

New Antigen targets?

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

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BREAST CANCER and HER2/neu

Total : 207,090

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

(USA)Total : 207,090

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One drug already targetting HER2 : Trastuzumab HERCEPTIN®

Recombinant humanised IgG1 monoclonal antibody

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BREAST CANCER and HER2/neu

Opportunities in different solid tumors expressing HER2/neu

• Breast

• Ovarian

• Colorectal

• Bladder

Initiate Phase 2 trial 1Q 2011

Lapuleucel-T NEUVENGE®39

HER2/neu

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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?

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

Active Cell Imunotherapy

New Antigen targets?

HER2/neu

CA-9

CEA

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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

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

phase 1 in Renal Cell Carcinoma planned in 2011

PIPELINE

Active Cell Imunotherapy

New Antigen targets?

HER2/neu

CA-9

CEA

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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

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DIFFICULTIES FOR ACI PRODUCTS DEVELOPMENT

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ACI

Long studies

Huge logistic

Ethic : vs placebo?

Exclusion of HIV, HepB- C

Manufacturing Antigens

Activ

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all M

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Market

Phase 3

Phase 2

Pre-clinical

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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

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Activation by agonist induces Ca++ to flow into cells

APOPTOSIS

TRPM8: Mechanism of Action

• This small molecule agonist is orally available

Clinical phase 1 trial ongoing

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AND NOW…CONQUEST OF THE WORLD ?

JUST A BEGINNING

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WHO’S NEXT?

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

DENDREON’S FIRST TARGET

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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 »

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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

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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

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TRIALS

D9902IMPACT D9901

MONEY

Provenge

Senior Notes

WHAT DO THEY NEED?

TRIALS & REGULATORY

• Advanced Therapy Medicinal Product (ATMP) Annex IV of directive 2003/63/CE

Cellular Therapy Via Centralised Procedure

Same dossier as for a medicinal product with technical

adaptations

• DENDREON wants to rely on its IMPACT trial, conducted in the US

BUT: Will it be acceptable in EU?

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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 changes impact of the

disease

Secondary endpoint: Time to objective disease survival

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

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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

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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

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• 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?

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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

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CONCLUSION

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SWOT

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?)

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EXPECTATIONS

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HIRING OPPORTUNITIES

Regulatory affairs

Quality assuranceManufacturin

g

Logistic coordinators

Sales & Marketing

R & D

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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

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YES!

WOULD WE JOIN DENDREON?

73FOR YOUR ATTENTION