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

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 Dendreon Presentation Transcript

  • Samia TharaSarah MerlenMatthieu Boulenger 1
  • 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
  • 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
  • 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
  • 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
  • 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
  • Active Cell Immunotherapy« Activates the body s ability to fight cancer » 7
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • MANUFACTURING• Incubation of Antigen-Presenting-Cell & Prostatic Antigen 40 hours APC-PAP-GM-CSF = Sipuleucel-T (PROVENGE®) 17
  • PATIENT INJECTION • Injection of Provenge® = APC-PAP-GMCSF • 3 days after Leukapheresis 19
  • SCHEME OF INJECTIONS Cost of 1 injection: $ 31,000Total cost of the treatment : $ 93,000 20
  • 22
  • PROVENGE MARKETProvenge® Provenge’s indication : treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer 23
  • 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
  • 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
  • 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
  • MANUFACTURING FACILITIES Los AngelesMid 2011 • New-Jersey : additional capacity expected in march 2011 • Atlanta & LA: additional capacity starting in mid-2011 28
  • PROPERTY & EQUIPMENT 127 427 76 235 12 285 1730 29
  • INFUSIONS CENTERSIncrease of number of Infusion centers by 9 fold in 2011 for DENDREON to be near their patients 30
  • 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
  • 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
  • PIPELINEExtension of Indication: Androgen Dependent Prostate Cancer (phase 3 : awaiting data on overall survival) Potential Raise of the market for PROVENGE® 33
  • PIPELINEActive Cell Imunotherapy New Antigen targets? HER2/neu CEA CA-9 34
  • PIPELINEActive Cell Imunotherapy New Antigen targets? HER2/neu CEA CA-9 35
  • 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
  • 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
  • BREAST CANCER and HER2/neuOne drug already targetting HER2 : Trastuzumab HERCEPTIN®  Recombinant humanised IgG1 monoclonal antibody 38
  • HER2/neuOpportunities in different solid tumors expressing HER2/neu • Breast • Ovarian • Colorectal • Bladder Initiate Phase 2 trial 1Q 2011 Lapuleucel-T NEUVENGE® 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?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
  • PIPELINEActive Cell Imunotherapy New Antigen targets? HER2/neu CEA CA-9 41
  • 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
  • PIPELINEActive Cell Imunotherapy New Antigen targets? HER2/neu CEA CA-9 43
  • 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
  • DIFFICULTIES FOR ACIPRODUCTS DEVELOPMENT Long studies Manufacturing Huge Antigens logistic ACI Exclusion Ethic : vs of HIV, placebo? HepB- C 45
  • Small Molecule Active Cellular Immunotherapies Pre-clinical Phase 2 Phase 3 Market46
  • 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
  • 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
  • WHO’S NEXT?World age-standardised rates (per 100,000 males) for prostate 51 cancer in 2008
  • 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
  • DIFFERENT STRATEGIES TO EXPAND OUTSIDE THE USA2 Strategies: Licensing OR To go alone ? 53
  • WHAT ABOUT LICENSING? 1998: license agreement : rights for PROVENGE in Asia and Pacific countries 2003 : released its rights for PROVENGE 54
  • 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
  • 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
  • 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 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
  • 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
  • PRIMARY ENDPOINTSurvival median : 4.1 months 60 Dendreon 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 61
  • 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
  • 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
  • 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
  • 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
  • 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
  • HIRING OPPORTUNITIES Quality assurance Manufacturing Logistic coordinatorsRegulatory affairs Sales & Marketing R&D 70
  • 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