Samia TharaSarah MerlenMatthieu Boulenger                     1
HISTORY                                         1992                                                                    Bi...
HISTORYAfter several years : Activated Cell Therapy• Activity shift : developing therapeutic products that fight cancerby ...
FUNDING•DENDREON came public in 2000 (NASDAQ) : $10 per share•Major shareholders:    o Mutual Fund : Fidelity Growth Compa...
ACTIVITY   DENDREON is focused on the discovery, development and commercialization:       •   of novel therapeutics      ...
CANCER THERAPIES• Cancer is characterized by abnormal cells that grow and proliferate,• forming masses called tumors• Canc...
Active Cell Immunotherapy« Activates the body s ability to fight cancer »                                                 ...
RESEARCH ACTIVITY•First step : to find antigens expressed on cancer cells that are suitable targets for cancer therapy    ...
RESEARCH ACTIVITYSecond step: to engineer antigens designed to stimulate and maximize cell-mediated immunity              ...
FIRST TARGET         In the mid-90’sPROSTATE CANCER                           10
ESTIMATED NEW CASESPROSTATE•Estimated new cases and deaths in 2010 (US) :New cases: 217,730Deaths: 32,050                 ...
PROSTATE CANCER      Diagnosis               Symptoms                        Stages•Average age when     •Often asymptomat...
PROVENGE®: Active Cell Immunotherapy      applied to Prostate Cancer3 actors:Recombinant antigen: composed of       Prost...
PRODUCTION & DELIVERY1                        14
LEUKAPHERESIS•In a cell collection center                                                3 to 4 hours•Antigen Presenting C...
PRODUCTION & DELIVERY        2           16
MANUFACTURING• Incubation of Antigen-Presenting-Cell & Prostatic Antigen                                 40 hours         ...
PRODUCTION & DELIVERY                 3      18
PATIENT INJECTION • Injection of Provenge® = APC-PAP-GMCSF • 3 days after Leukapheresis                                   ...
SCHEME OF INJECTIONS    Cost of 1 injection: $ 31,000Total cost of the treatment : $ 93,000                               ...
A HUGE LOGISTIC                  21
22
PROVENGE MARKETProvenge®      Provenge’s indication : treatment of asymptomatic or minimally symptomatic metastatic       ...
PROVENGE MARKET                  24
PROVENGE SALES                                                               Total in 2010 : $48 M• About only 500 patient...
What’s next for PROVENGE in the              USA?Expectations in 2014:•Market shares = 35%•Patients treated= 38,628     BU...
Supply of the recombinant                          Antigen  • DENDREON        doesn’t produce           the antigen itself...
MANUFACTURING FACILITIES Los AngelesMid 2011 • New-Jersey : additional capacity expected in march 2011 • Atlanta & LA: add...
PROPERTY & EQUIPMENT                            127 427                   76 235          12 285   1730                   ...
INFUSIONS CENTERSIncrease of number of Infusion centers by 9 fold in 2011 for DENDREON to be                              ...
OTHER ISSUES FOR 2011 SALES FORCES • Increase of the sales forces to approximatly 100 reps to service 450 centers by the e...
EMERGING COMPETITORS FOR       PROSTATE CANCERTrade name       Type of treatment    Company             PhasePROSTVAC®    ...
PIPELINEExtension of Indication:   Androgen Dependent Prostate Cancer                              (phase 3 : awaiting dat...
PIPELINEActive Cell Imunotherapy          New Antigen targets?       HER2/neu                               CEA           ...
PIPELINEActive Cell Imunotherapy          New Antigen targets?       HER2/neu                               CEA           ...
HER2/neu= Human Epidermal Growth Factor Receptor 2Membrane Glycoprotein involved in cell growth and differenciationCompose...
BREAST CANCER and HER2/neu Total : 207,090                             (USA)Total : 207,090              The HER2 protein ...
BREAST CANCER and HER2/neuOne drug already targetting HER2 : Trastuzumab HERCEPTIN®         Recombinant humanised IgG1 mo...
HER2/neuOpportunities in different solid tumors expressing HER2/neu                  • Breast                  • Ovarian  ...
BLADDER CANCER & HER2/neu    Bladder cancer : 70,530 new cases in 2010 (USA)                            The 4th most frequ...
PIPELINEActive Cell Imunotherapy          New Antigen targets?       HER2/neu                               CEA           ...
CA-9•In-licensed from Bayer Corporation, Business Group Diagnostics= Carbonic Anhydrase IX•Transmembrane protein involved ...
PIPELINEActive Cell Imunotherapy          New Antigen targets?       HER2/neu                               CEA           ...
CEA• In-licensed from Bayer Corporation, Business Group Diagnostics=CarcinoEmbryonic Antigen : glycoprotein involved in ce...
DIFFICULTIES FOR ACIPRODUCTS DEVELOPMENT                        Long                       studies   Manufacturing        ...
Small Molecule   Active Cellular Immunotherapies                      Pre-clinical                                     Pha...
TRPM8=Transient Receptor Potential Cation Channel subfamily M member 8• transmembrane cation channel identified through De...
TRPM8: Mechanism of ActionActivation by agonist           induces Ca++ to flow into cells APOPTOSIS  •This small molecul...
AND NOW…CONQUEST OF THE       WORLD ?                          49
JUST A BEGINNING                   50
WHO’S NEXT?World age-standardised rates (per 100,000 males) for prostate                                                  ...
DENDREON’S FIRST TARGET     EUROPE « Europe is our first ex-US opportunity »•Market for metastatic AIPC patients = 1.5X to...
DIFFERENT STRATEGIES TO    EXPAND OUTSIDE THE USA2 Strategies:                 Licensing                    OR            ...
WHAT ABOUT LICENSING?      1998: license agreement : rights for    PROVENGE in Asia and Pacific countries               20...
LICENSING?Advantages• Greater local knowlege of the Regulatory agencies by the licensee. • Better manufacturing capacity o...
DENDREON’S CHOICE : to go             alone in EUROPEWhy this choice?•2 hypothesis:                                       ...
WHAT DO THEY NEED?         TRIALS               MONEYIMPACT   D9901    D9902   Provenge   Senior Notes
TRIALS & REGULATORY• Advanced Therapy Medicinal Product (ATMP) Annex IV of directive  2003/63/CE              Cellular Th...
IMPACT TRIAL•Randomized              •512 men             •Primary endpoint :•Double-blind            •With asymptomatic  ...
PRIMARY ENDPOINTSurvival median : 4.1 months                                                  60                          ...
IMPACT TRIAL:            NEGATIVE POINTS?IMPACT TRIAL   Primary endpoint: Overall survival         trials done versus pl...
REIMBURSEMENT CHALLENGEMarket access and reimbursement success is key to realizing full product potential inE.U.Key factor...
WHERE TO HAVE A PLACE?• Find a strategic place in EUROPE        wich must be:                Near airport and road networ...
WHERE TO HAVE A PLACE?• During DENDREON submits an European authorization (late 2011/early 2012)           Initial manufac...
WITH WICH MONEY? Revenues from Provenge : $48 millions in 2010 January, 14th 2011: Dendreon announced the pricing of a p...
CONCLUSION             66
Strengths                                          Weaknesses- ACI : revolutionary therapeutic approach          - Huge lo...
68
EXPECTATIONS               69
HIRING OPPORTUNITIES                           Quality assurance    Manufacturing                                         ...
WOULD WE JOIN                        DENDREON?Cancer treatment is a «   noble » domainWorking for a revolutionary proces...
WOULD WE JOIN DENDREON?       YES!                          72
FOR YOUR ATTENTION   73
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Dendreon

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5e année Industrie - projet de groupe "Business model: Dendreon"

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  • CMS = CENTERS FOR MEDICARE AND MEDICAID SERVICE Svt les assurances privees suivent les tx de remboursement de medicaid et medicare  plus de patients pourront avoir acces au ttmt
  • entraine l'internalisation du récepteurs HER2, ce qui le rend inactif ; bloque leur dimérisation donc aucune activité kinase n’est possible ; stimule la formation de tétramère de protéine Her2, une conformation non propice à l’activité kinasique. Chacun de ces trois mécanismes empêchent l'activation des récepteurs HER2 et donc la prolifération cellulaire
  • Dendreon

    1. 1. Samia TharaSarah MerlenMatthieu Boulenger 1
    2. 2. HISTORY 1992 Biotechnology company called: Activated Cell Therapy Moutain View, CaliforniaDr Edgar Dr SamuelEngleman Strobber •First activity : isolating hematopoietic stem cells from blood for use in patients with cancer who require transplantation. 2
    3. 3. HISTORYAfter several years : Activated Cell Therapy• Activity shift : developing therapeutic products that fight cancerby manipulating aspects of the immune system Seattle, Washington state « Targeting Cancer, Transforming Lives »• Today: o CEO : Mitchell H. Gold o 650 employees (April 2010) o Main Manufacturing facility in Morris Plain (NJ) 3
    4. 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 4
    5. 5. ACTIVITY DENDREON is focused on the discovery, development and commercialization: • of novel therapeutics • that may significantly improve cancer treatment options for patientsPhilosophy of Dendreon : produce Active Cellular Immunotherapy products stimulate an immune response against a variety of tumor types 5
    6. 6. CANCER THERAPIES• Cancer is characterized by abnormal cells that grow and proliferate,• forming masses called tumors• Cancer therapies must eliminate or the growth of the cancer control Chemotherapy Hormone treatments Surgery Radiation•BUT : may not have the desired therapeutic effect may result in significant detrimental side effects New approach to Cancer Treatment: IMMUNOTHERAPIES 6
    7. 7. Active Cell Immunotherapy« Activates the body s ability to fight cancer » 7
    8. 8. RESEARCH ACTIVITY•First step : to find antigens expressed on cancer cells that are suitable targets for cancer therapy Internal antigen License discovery program agreements 8
    9. 9. RESEARCH ACTIVITYSecond step: to engineer antigens designed to stimulate and maximize cell-mediated immunity Creation of the “Antigen Delivery Cassette™” = The key to robuste immune response Aim : to raise the quality and the quantity of the immune response 9
    10. 10. FIRST TARGET In the mid-90’sPROSTATE CANCER 10
    11. 11. ESTIMATED NEW CASESPROSTATE•Estimated new cases and deaths in 2010 (US) :New cases: 217,730Deaths: 32,050 11 The second most common type of cancer among men in the USA
    12. 12. PROSTATE CANCER Diagnosis Symptoms Stages•Average age when •Often asymptomatic •Low growthdiagnosed:70 years at the beginning•Physical examination •Pain •Hormono- dependant• Dosing •Difficulty in urinating Prostate Specific •Problems during Antigen sexual intercourse•Biopsy => Gleason •Erectile dysfunction •Hormono-score independant • Such as Benign after one to three years and resume growth despite hormone therapy. Prostatic Hyperplasia 12
    13. 13. PROVENGE®: Active Cell Immunotherapy applied to Prostate Cancer3 actors:Recombinant antigen: composed of Prostatic Acid Phosphatase (expressed in more than 95% ofprostate cancers cells) GM-CSF : Granulocyte-macrophage colony-stimulating factorAntigen Presenting Cell: white blood cells removed from thepatient through LEUKAPHERESIST-Cells: actived by the APC-PAP-GM-CSF, attack the tumor cells 13
    14. 14. PRODUCTION & DELIVERY1 14
    15. 15. LEUKAPHERESIS•In a cell collection center 3 to 4 hours•Antigen Presenting Cells are removed•Rest of the blood is returned to the patient 15
    16. 16. PRODUCTION & DELIVERY 2 16
    17. 17. MANUFACTURING• Incubation of Antigen-Presenting-Cell & Prostatic Antigen 40 hours APC-PAP-GM-CSF = Sipuleucel-T (PROVENGE®) 17
    18. 18. PRODUCTION & DELIVERY 3 18
    19. 19. PATIENT INJECTION • Injection of Provenge® = APC-PAP-GMCSF • 3 days after Leukapheresis 19
    20. 20. SCHEME OF INJECTIONS Cost of 1 injection: $ 31,000Total cost of the treatment : $ 93,000 20
    21. 21. A HUGE LOGISTIC 21
    22. 22. 22
    23. 23. PROVENGE MARKETProvenge® Provenge’s indication : treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer 23
    24. 24. PROVENGE MARKET 24
    25. 25. 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 market7300 patients we can expect a large progression 25
    26. 26. 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 26
    27. 27. Supply of the recombinant Antigen • DENDREON doesn’t produce the antigen itself• The company utilizes third party suppliers tomanufacture and package the recombinant antigene• First collaboration :• Since September 2010 , second supplier : 27
    28. 28. MANUFACTURING FACILITIES Los AngelesMid 2011 • New-Jersey : additional capacity expected in march 2011 • Atlanta & LA: additional capacity starting in mid-2011 28
    29. 29. PROPERTY & EQUIPMENT 127 427 76 235 12 285 1730 29
    30. 30. INFUSIONS CENTERSIncrease of number of Infusion centers by 9 fold in 2011 for DENDREON to be near their patients 30
    31. 31. OTHER ISSUES FOR 2011 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 capacityREIMBURSEMENT• 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 31
    32. 32. EMERGING COMPETITORS FOR PROSTATE CANCERTrade name Type of treatment Company PhasePROSTVAC® Viral vector Bavarian Nordic Phase II completedGVAX GM-CSF gene- BioSante Phase III transfected cell Pharmaceuticals vaccinesDCVAX Prostate Cellular vaccine Northwest Phase III BiotherapeuticsTROVAX® Viral vector Oxford Biomedical Phase IIIIPILIMUMAB Monoclonal antibodies BMS Phase IIIABIRATERONE Hormonotherapy Janssen-Cilag Phase III 32
    33. 33. PIPELINEExtension of Indication: Androgen Dependent Prostate Cancer (phase 3 : awaiting data on overall survival) Potential Raise of the market for PROVENGE® 33
    34. 34. PIPELINEActive Cell Imunotherapy New Antigen targets? HER2/neu CEA CA-9 34
    35. 35. PIPELINEActive Cell Imunotherapy New Antigen targets? HER2/neu CEA CA-9 35
    36. 36. HER2/neu= Human Epidermal Growth Factor Receptor 2Membrane Glycoprotein involved in cell growth and differenciationComposed of:• an extracellular domain for binding ligands• a single transmembrane segment• an intracellular domain carrying tyrosine-kinase activity 36
    37. 37. BREAST CANCER and HER2/neu Total : 207,090 (USA)Total : 207,090 The HER2 protein is overexpressed in about 30% of all breast cancers 37
    38. 38. BREAST CANCER and HER2/neuOne drug already targetting HER2 : Trastuzumab HERCEPTIN®  Recombinant humanised IgG1 monoclonal antibody 38
    39. 39. HER2/neuOpportunities in different solid tumors expressing HER2/neu • Breast • Ovarian • Colorectal • Bladder Initiate Phase 2 trial 1Q 2011 Lapuleucel-T NEUVENGE® 39
    40. 40. 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 Neuvenge® targeting HER2 in cancer : Vs HERCEPTIN? bladder cancer : Vs placebo? 40
    41. 41. PIPELINEActive Cell Imunotherapy New Antigen targets? HER2/neu CEA CA-9 41
    42. 42. 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 knownTumors over-expressing CA-9: •Colon •Cervical •Kidney CA-9 is overexpressed in 75% of Renal cell Carcinoma phase 1 in Renal Cell Carcinoma planned in 2011 42
    43. 43. PIPELINEActive Cell Imunotherapy New Antigen targets? HER2/neu CEA CA-9 43
    44. 44. 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 smokersCancers expressing CEA : • Breast (65%) • Lung (70%) Phase 1 expected in 2012 • Colon 44
    45. 45. DIFFICULTIES FOR ACIPRODUCTS DEVELOPMENT Long studies Manufacturing Huge Antigens logistic ACI Exclusion Ethic : vs of HIV, placebo? HepB- C 45
    46. 46. Small Molecule Active Cellular Immunotherapies Pre-clinical Phase 2 Phase 3 Market46
    47. 47. TRPM8=Transient Receptor Potential Cation Channel subfamily M member 8• transmembrane cation channel identified through Dendreon’s internal antigen discoveryprogram Patent on the gene in 2001Over-expressed in :• 100% of prostate cancers• 71% of breast cancers• 93% of colon cancers Attractive target• 80% of lung cancers Synthesis of small molecule agonists 47
    48. 48. TRPM8: Mechanism of ActionActivation by agonist  induces Ca++ to flow into cells APOPTOSIS •This small molecule agonist is orally available Clinical phase 1 trial ongoing 48
    49. 49. AND NOW…CONQUEST OF THE WORLD ? 49
    50. 50. JUST A BEGINNING 50
    51. 51. WHO’S NEXT?World age-standardised rates (per 100,000 males) for prostate 51 cancer in 2008
    52. 52. DENDREON’S FIRST TARGET 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 » 52
    53. 53. DIFFERENT STRATEGIES TO EXPAND OUTSIDE THE USA2 Strategies: Licensing OR To go alone ? 53
    54. 54. WHAT ABOUT LICENSING? 1998: license agreement : rights for PROVENGE in Asia and Pacific countries 2003 : released its rights for PROVENGE 54
    55. 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 55
    56. 56. DENDREON’S CHOICE : to go alone in EUROPEWhy this choice?•2 hypothesis: They want 100% of worldwide rights Own will of DENDREON They don’t want to share their revenues Corporate image of growth Choice by default: they didn’t find any partners? No certitude to get an european •Too risky? approval Reimbursement? Provenge « is not just a pill in a bottle » 56
    57. 57. WHAT DO THEY NEED? TRIALS MONEYIMPACT D9901 D9902 Provenge Senior Notes
    58. 58. 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 USBUT: Will it be acceptable in EU? 58
    59. 59. IMPACT TRIAL•Randomized •512 men •Primary endpoint :•Double-blind •With asymptomatic Overall survival•Multicenter •Or minimally •Secondary endpoint: symptomatic MPC •Time to objective disease progression VS Placebo 59 Dendreon website
    60. 60. PRIMARY ENDPOINTSurvival median : 4.1 months 60 Dendreon website
    61. 61. 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 61
    62. 62. REIMBURSEMENT CHALLENGEMarket access and reimbursement success is key to realizing full product potential inE.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. 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 63
    64. 64. WHERE TO HAVE A PLACE?• 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!! 64
    65. 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 65
    66. 66. CONCLUSION 66
    67. 67. Strengths Weaknesses- ACI : revolutionary therapeutic approach - Huge logistic :  Expensive- ACI : less AEs than chemotherapy  Restrictions for Clinical trials- One drug on the market at least : Provenge - Provenge sales too low compared to  revenues expectations- Huge logistic : difficult to copy for generics - Increase of debts (senior notes) - No profit yet SWOT Opportunities Threats- Expansion -Decision for reimbursment of Provenge  In the USA expected in March  In Europe : similarity with US market - Emerging competitors-Provenge : new indication in development - At the mercy of the EMA for the approval of Provenge (clinical trial vs. Taxotere?)- ACI : repeatible with new Antigens  other cancers targeted 67
    68. 68. 68
    69. 69. EXPECTATIONS 69
    70. 70. HIRING OPPORTUNITIES Quality assurance Manufacturing Logistic coordinatorsRegulatory affairs Sales & Marketing R&D 70
    71. 71. WOULD WE JOIN DENDREON?Cancer treatment is a « noble » domainWorking for a revolutionary process as ACI must be exciting Transition from a total R&D to a fully-integrated commercial company Development of domains corresponding to our professional expectations Regulatory Challenge in Europe Development of new ACI products New jobs in Regulatory Affairs Evaluation of new markets 71
    72. 72. WOULD WE JOIN DENDREON? YES! 72
    73. 73. FOR YOUR ATTENTION 73

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