Biotecnología

IESE – 11 de marzo de 2010

BIOTECNOLOGÍA

Toda aplicación tecnológica que utilice sistemas

biológicos y organismos vivos o sus derivados para

la creación o modificación de productos o procesos

para usos específicos.

QUÉ SISTEMA BIOLÓGICO ? QUÉ ORGANISMO VIVO?

VIRUS

CÉLULAS PROCARIOTAS Bacterias

CÉLULAS EUCARIOTAS: Células Animales Células Vegetales Hongos

CREACIÓN O MODIFICACIÓN DE PRODUCTOS O PROCESOS

UTILIZARLOS PARA LA PRODUCCIÓN DE

PRODUCTOS

MODIFICARLOS PARA LA PRODUCCIÓN DE

PRODUCTOS Aumentando su productividad Haciendo que fabriquen productos nuevos Reparando sus ineficacias Activando o inhibiendo sus procesos

DEL ADN A LAS PROTEINAS PASANDO POR EL

ARN

LAS CÉLULAS CONTIENEN

Nucleo donde reside el ADN: un hardware de base 4 (citosina, timina, adenina y guanina): CTAG.

Un citoplasma donde reside la fabrica de proteinas: un hardware de base 20: los aminoácidos esenciales.

Una membrana que las envuelve.

ENTENDIENDO LA VIDA. UN DOBLE HARDWARE

El DNA ES UNA SOPA DE LETRAS QUE ALMACENA TODA LA INFORMACION MEDIANTE

UN SENCILLO ALFABETO DE 4 LETRAS (A,C,G,T,)

ATGTTGACCTGATCGAAATGGATCCTCTCTCGACTATAACCAATGATGGAAATGGATCATGTTGACCTGATCGATCCTCTCTCGACTTTGACCTGCATGATGCCTAGCATGTTGACCTGATCGAAATGGATCCTCTCTCGACTAGGATCCTCTCTCGACTATAACCAATGATGCCTAGCACATGTTGACCTGCGACTATAACCAATGATGCCTAGCATGTTGACCTGATCGAAATGGATCCTAGCCAATGATGCCTAGCCAATGATGCCTAGCATGATGCCTAGCTTGTGGATCCTCTCTCGACTATAACCAATGATGCCTAGATGTTGACCTGATGGATCCTCTCTCGACTATAACCAATGATGCCTAGCACATGTTGACCTGCCTGATCGAAATGGATCCTCTCTCGACTATAACCAATGATGCCTAGCAATGTTGACCTGATCGAAATGGATCCTCTCTCGACTATAACCAATGATGCTAGCCAATGATGCCTAGCCAATGATGCCTAGCATGATGCCTAGCTTGGACTATAACCAATGATGCCTAGCACATGTTCTAGCCAATGATGCACATGTTCTAGCCCTAGCCAATGATGCCTAGCATGATGCCTAGCTTGTGATG

CÓDIGO GENÉTICOCÓDIGO GENÉTICO. Es el conjunto de normas por las que la información codificada en el material genético (secuencias de ADN o ARN) se traduce en proteínas en las células vivas. El código define la relación entre secuencias de tres nucleótidos, llamadas codones, y los aminoácidos. La secuencia de codones determina la secuencia de una proteína en concreto, que tendrá una estructura y una función específicas

SÍNTESIS DE PROTEÍNAS

LOS GENES SON FRASES CON SIGNIFICADO FORMADAS POR PALABRAS DE TRES LETRAS

ATGCCTACTT ATG CCA TTG ATTCCCAA

aa1 aa2 aa3 PROTEINA

Genes

Proteína

Función

Pérdida de función

ENFERMEDAD

Mutación

DNAP exón 1 exón 2 exón 3

TranscripciónSplicing

RNA

proteína

traducción

LOS GENES ESTAN FRAGMENTADOS

Intrón 1 Intrón 2

BIOTECNOLOGIA Y MEDICINA

CREACIÓN O MODIFICACIÓN

El ADN como objetivo: repararlo, modificarlo

Trabajar sobre el ARN: interfiriendo

Las proteínas como objetivo: reparándolas, produciéndolas con eficiencia

Las membranas: la barrera a superar y/o fuente de medicamentos

MODIFICANDO EL ADN

INTRODUCIR EL CÓDIGO DE UNA PROTEÍNA EN UNA CÉLULA BACTERIANA, VEGETAL O ANIMAL CON EL OBJETIVO DE PRODUCIRLA:

Problema: cómo pasar las membranas.

Qué se patenta: el método de modificación vinculado al sustrato y al producto obtenido, los usos del producto obtenido por dicho método, las formas galénicas, etc.

EJEMPLOS

PRODUCIDO POR CELULAS BACTERIANAS: ESCHERICHIA COLI: www.merckserono.com

INTERFERON ALFA 2B: www.schering-plough.es

PRODUCIDO POR CÉLULAS DE MAMIFERO: EFALIZUMAB: www.merckserono.com

INTERFERON BETA 1A: www.merckserono.com

ERITOPROYETINA: www.roche.es

PRODUCIDAS EN CÉLULAS VEGETALES DE ZANAHORIA: www.protalix.com

REPARANDO EL ADN

EL SUEÑO DE LA TERAPIA GÉNICA: en cultivos celulares ya se ha conseguido reparar y reproducir el ADN reparado pero en animales aún tenemos que resolver:

llegar a la célula diana.

Atravesar la membrana celular.

Llegar al núcleo.

EN QUÉ SE INVESTIGA

SOBRE LA MEMBRANA CELULAR: CÓMO RECONOCERLA SELECTIVAMENTE: PROTEÍNAS DE MEMBRANA.

SOBRE CÓMO TRASPASAR LA MEMBRANA CELULAR: VÍAS ESPECIALES DE ENTRADA, LIPOSOMAS, ETC.

CÓMO LLEGAR AL NÚCLEO:

Vectores víricos.

Mecanismos inversos: del citoplasma al núcleo.

Qué se patenta: todo aquello que no es un descubrimiento: el uso de proteínas como efecto diana, los liposomas y sus usos, etc.

INTERFIRIENDO EL ARN

www.sirna.com

The scientific community considers RNA

interference the breakthrough biological

discovery of the decade with the potential to

change how diseases are treated. Sirna

Therapeutics is at the forefront of the effort to

create RNAi-based therapies and leverage the

vast potential of this technology to ultimately

treat patients.

ARN

iRNA - PROBLEMAS Y OPORTUNIDADES

TECHNOLOGY PLATFORM – DRUG DELIVERY

Novel polymers and lipids for encapsulation that exhibitLow toxicity

Molecular Targeting

LOCAL DELIVERY

Medium and high throughput screening techniques for siRNA quantitation

Assays for clinical biodistribution

Assays for pharmacodynamic evaluation of miRNA activity

High-throughput in vivo screening technologies for determining mRNA silencing

LA PRODUCCIÓN DE PROTEÍNAS

REPARANDO EL STOP

www.ptctherapeutics.com

REPARANDO LA ESTRUCTURA ESPACIAL

www.amicus.com

PRODUCIÉNDOLAS CON EFICIENCIA

www.erabiotech.com

LAS MEMBRANAS

FUENTE DE MEDICAMENTOS

Creando vacunas

www.archivelfarma.com: tuberculosis

www.immatics.com: cáncer

Buscando ventanas de entrada:

www.gp-pharm.com: liposomas target

Canales iónicos de membrana

EVALUAR PROYECTOS Y COMPAÑIAS

• Informacion sobre drogas huerfanas

• Datamonitor

• Clasificacion de las enfermedades

• IMS

ENFERMEDADES POR ORDEN DECRECIENTE DE PREVALENCIA

PREVALENCIA ESTIMADA(/100 000)

Polydactyly postaxial 50,0

Gelineau disease 49,0

Gullain-Barré syndrome 47,5

Melanoma, familial 46,8

Squamous cell carcinoma of head and neck 46,0

Autism 45,0

Tetralogy of Fallot 45,0

Deafness, autosomal recessive, nonsyndromic, sensorineural, type DFNB 44,0

Arrhytmogenic right ventricular dysplasia 43,5

Meniere's dissease 42,5

NOMBRE DE ENFERMEDADES

ORPHAN DRUG DEVELOPMENT AND APPROVAL TRENDS

0

20

40

60

80

100

120

140

160

1801

99

0

19

91

19

92

19

93

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

20

08

H1

Designations ApprovalsH12009= Q1 2009 + Q22009

Number of designated and approved orphan drugs in the US, 1993 – Q2 2009

ORPHAN DRUG DEVELOPMENT AND APPROVAL TRENDS

0

10

20

30

40

50

60

70

80

90

100

2000

2001

2002

2003

2004

2005

2006

2007

2008

H1

2009

Designations Approvals Withdrawn/suspended RefusedH12009= Q1 2009 + Q22009

Number of designated, approved, withdrawn/suspended and refused orphan drugs in the EU, 2000 – Q2 2009

MARKET DEFINITION – Cancer Market

CLASS ATC CLASS REPORT CLASSIFICATION

Targeted therapies L1x3: Antineolastic monoclonal antibodies

Monoclonal antibodies

L1X9: All other antineoplastics*** Small molecules

Cytotoxic therapies L1A: Alkylating agents DNA-interactive agentsL1B: Antimetabolites AntimetabolitesL1C: Vinca alkaloids & other plant-derived products

DNA-interactive agents* or Mitotic inhibitors

L1D: antineoplastic antibiotics DNA-interactive agentsL1X2: Pantinum compunds DNA-interactive agents

Antihormonal therapies L2A3: LHRH analogs (agonists) LHRH agonistsL2B1: Anti-estrogens Anti-estrogensL2B2: Anti-androgens Anti-androgensL2B3: Aromatase inhibitors Aromatase inhibitorsL2B9: Other hormone antagonists Other hormone antagonists

DEFINITION OF THE CANCER MARKET, 2009

Note: The L2A3 class comprises LHRH analogs but for the purpose of this report it will be defined as "LHRH agonists". LHRH antagonists are classified under the L2B9 class: other hormone antagonists.

DNA = deoxyribonucleic acid; LHRH = luteinzing hormone-releasing hormone

Source: Datamonitor

EXECUTIVE SUMMARY

PIPELINE PRODUCT 2007 2009 2011 2013 2015 2017

Vimpat 0 104 303 405 454 483Transacin 0 72 175 203 223 237Zenvia 0 0 112 165 186 81XP13512 0 54 452 475 492 206Gabapentin GR 0 0 47 75 84 92NP-1 0 0 73 106 117 127Ralfinamide 0 0 37 89 105 114

Total new products 0 230 899 1.217 1.361 1.341

Marketed products 2.275 3.650 4.404 4.689 4.506 4.989

Total Market 2.275 3.880 5.303 5.906 5.867 6.330

*2007 data is historic data from MIDAS Sales Data, IMS Health, March 2008.Source: Datamonitor

SALES FORECAST ($m) of key pipeline products in neuropathic pain, 2007-2017

EXECUTIVE SUMMARY

Molecule Brand 2008 2010f 2012f 2014f 2016f 2018fCAGR

2008-2018

Seven major markets 13.740 16.998 17.902 18.292 17.947 18.728 3,1

Alkylating agents 1.150 1.324 1.441 1.474 1.314 1.314 1,6Bendamustine Treanda 85 119 163 201 169 169 7,1

Generics 0 0 0 0 46 63 -Temozolomide Temodar 703 719 737 683 424 413 -5,2

Generics 0 91 127 156 226 235 -Rest of class* Brands 248 263 266 268 269 270 0,9

Generics 114 131 148 165 178 190 5,3

Antimetabolites 4.401 5.771 6.669 6.765 6.715 7.143 5,0Azacitidine Vidaza 181 399 439 598 816 1.004 18,7

Generics 0 0 46 81 86 89 -Capecitabine Xeloda 708 911 1.174 1.085 539 537 -2,7

Generics 0 0 0 90 307 321 -Clofarabine Clolar 18 102 156 82 76 78 15,9

Generics 0 0 12 53 64 70 -Decitabine Dacogen 156 318 659 779 894 1.111 21,7

Generics 0 0 0 59 105 112 -Gemcitabine Gemzar 1.268 1.290 1.394 922 658 631 -6,7

Generics 0 116 169 313 391 399 -Nelarabine Arranon 10 69 136 140 153 179 33,7

Generics 0 0 0 12 19 21 -

Commercial Insight: Cytotoxic TherapiesSource: Datamonitor (06/2009)

CYTOTOXIC THERAPY SALES FORECASTS IN THE SEVEN MAJOR MARKETS ($m), 2008-2018

AGENTES ALQUILANTES

BUSINESS NEWS

Biovitrum sells anti-obesity programme to AstraZenecaAstrazeneca is to pay biovitrum up to €186 million for its preclinical leptin.

Novartis to pay up to $620 million for CortheraNovartis is to acquire the privately held US biopharmaceutical company Corthera for $120 million up front and up to $500 million in development and commercialisation milestones.

Teva signs pact for OncoGenex’s cancer adjunctTeva is to pay $60 million up front and up to $370 million in milestones to access OncoGenex’s lead product, the cancer adjunct therapy candidate OGX-011.

Novartis venture arm inks $200M deal with tiny ViametTiny Viamet Pharmaceuticals in Morrisville, NC has snared a $200 million licensing option deal with the venture arm of Swiss pharma giant Novartis.

TOP 20 BIOTECH VENTURE CAPITAL DEALS OF 2009

1. Clovis Oncology - $146.30 million2. Zogenix - $70.96 million3. BioVex Group - $70 million4. Pacific Biosciences - $68 million5. Hyperion Therapeutics - $68 million6. Anacor Pharmaceuticals $50 million6. Proteon Therapeutics $50 million6. PTC Therapeutics $50 million9. Virdante Pharmaceuticals - $47.75 million10. Cempra Pharmaceuticals - $46 million11. Complete Genomics - $45 million11. SFJ Pharmaceuticals - $45 million13. Amyris Biotechnologies - $41.75 million14. Kolltan Pharmaceuticals - $40.50 million15. Ironwood Pharmaceuticals - $40 million15. Epizyme - $40 million15. Adamas Pharmaceuticals - $40 million15. Aileron Therapeutics - $40 million15. Regado Biosciences - $40 million20. GlycoMimetics - $38.98 million

BIOSCIENCE VALUATIONCompany valuation- June 2007 -

Sarcodoxome®


Valuation approach and methods (I)

• The valuation model considers relevant value drivers such as the potential number of patients treated, product price, risks and costs. Discrete and continuous probability distributions are used to model major uncertainties.

CurrentCompetitors

TargetPopulation

FutureCompetitors

# PatientsTreated

Pharmaco-economics

BenchmarkPrices

ProductPrice

CostAssumptions

R&DRisks

RevenueProjections

Cash FlowModel

AugmentedNPV


(All in EUR million)

ProjecteNPV(USA)

eNPV(EU5)

eNPVto GP Pharm

Lutrate® 34 6 39

Sarcodoxome® 21 23 43

Crodox® 5 7 13

Octreotide SAR 4 1 4

Octreotide MAR 4 2 6

Octreotide LAR 0 0 0

Risperidone depot 48 10 57

FOD + simvastatin 21 21

Contract manufacturing 38

Company value

NPV Analysis

223

(All in EUR million)

ProjecteNPV(USA)

eNPV(EU5)

eNPVto GP Pharm

Lutrate® 34 6 39

Sarcodoxome® 21 23 43

Crodox® 5 7 13

Octreotide SAR 4 1 4

Octreotide MAR 4 2 6

Octreotide LAR 0 0 0

Risperidone depot 48 10 57

FOD + simvastatin 21 21

Contract manufacturing 38

Company value

NPV Analysis

223

Project values (including partnering scenarios) and company value

• The project values provided on the previous slide do not include potential partnering scenarios.

• However, it is assumed that GP Pharm will license out the projects to big or mid-sized marketing partners. In any partnering agreement, both parties share the value of the project.

• Based on the expected value split, GP Pharm’s value resulting from a project-by-project analysis is EUR 223 million.

• Risperidone depot and Sarcodoxome® and are the development projects with the highest values, followed by Lutrate® and the contract manufacturing business.

• The contract manufacturing business represents a stable value, which is not expected to change significantly over time. The R&D projects, however, have the potential to gain value with every successful completion of a milestone.

• It should be noted that the actual value of GP Pharm may be significantly higher due to ownership of assets that have not been explicitly valued (e.g., land, manufacturing facilities). Furthermore, the analysis ignores the value generated from sales in countries not evaluated here (based on IMS Health almost 80% of global retail sales are generated in the USA and EU5).

Note: sum of project values may not add to 223 due to rounding errors.


MCap

(€ M)

Acusphere ACUS 116 109 USA

Adventrx ANX 24 162 USA

Ambrilia Biopharma AMB 28 53 Canada

Antigenics AGEN 100 138 USA

BioDelivery Sciences

BDSI 13 96 USA

Celsion CLN 29 34 USA

Labopharm DDSS 98 270 Canada

NeoPharm NEOL 53 37 USA

Novavax NVAX 56 142 USA

pSivida PSDV 55 58 Australia

Sonus Pharmaceuticals SNUS 61 150 USA

YM BioSciences YMI 14 71 Canada

Company EmployeesSymbol Country

Company value and comparables

• As shown in a previous slide, the core company value for GP Pharm resulting from a project-by-project analysis is EUR 223 million.

• The mean value for public companies with a comparable profile to GP Pharm is EUR 110 million (see adjoining table).

• The higher value of GP Pharm can be explained by GP Pharm’s contract manufacturing business and an intelligent portfolio mix consisting of a) several late-stage projects with low remaining R&D risk (Lutrate®, Sarcodoxome®) and b) early-stage projects with a high commercial potential and comparably low development risk (risperidone depot, FOD + simvastatin).

• The listed public companies match GP Pharm because they have a- focus on or at least strong activities in the areas of reformulation or drug delivery,- market capitalization of less than EUR 500 million, - staff below 200 employees.

Mean = EUR 110 million

In summary, Bioscience Valuation believes that GP Pharm is fairly valued at about EUR 220 million. Note that this valuation does not consider drug sales in countries other than the EU5 and USA, nor does it fully consider all assets of GP Pharm (such as, e.g., land and facilities). Both factors tend to increase GP Pharm’s value beyond the EUR 223 million that results from Bioscience Valuation’s analysis.


Sarcodoxome®

-Assumptions

Sarcodoxome®


Product profile

Source:Team meeting at GP Pharm

USPs:1. First registered therapy for STS2. Less cardiotoxicity3. No hand-foot syndrome

USPs:1. First registered therapy for STS2. Less cardiotoxicity3. No hand-foot syndrome

Sarcodoxome®

Sarcodoxome® (liposomal doxorubicin)

Target Product Profile

Soft tissue sarcoma (STS)

First line therapy for the treatment of patients with locally advanced or metastatic STS

Efficacy:

- Non-inferior to free doxorubicin:

OR (overall response) = 16% - 27%

Safety/Tolerability:

- Clinically significant superior to free doxorubicin:

a) less cardiotoxicity

b) no palmar-plantar erythrodysesthesia (hand-foot syndrome)

- At least as tolerable as free doxorubicin with respect to hematological side effects,

particularly neutropenia.

Formulation:

- Intravenous infusion, 70 mg/m2

- One infusion every three weeks for 30'

- Average of four treatment cycles per patient

Sarcodoxome® (liposomal doxorubicin)

Target Product Profile

Soft tissue sarcoma (STS)

First line therapy for the treatment of patients with locally advanced or metastatic STS

Efficacy:

- Non-inferior to free doxorubicin:

OR (overall response) = 16% - 27%

Safety/Tolerability:

- Clinically significant superior to free doxorubicin:

a) less cardiotoxicity

b) no palmar-plantar erythrodysesthesia (hand-foot syndrome)

- At least as tolerable as free doxorubicin with respect to hematological side effects,

particularly neutropenia.

Formulation:

- Intravenous infusion, 70 mg/m2

- One infusion every three weeks for 30'

- Average of four treatment cycles per patient


Decision tree Sarcodoxome®

• This decision tree illustrates the most relevant milestones in the development of Sarcodoxome® for STS, providing the assumed timing for these milestones (provided by GP Pharm) and their individual probability of success (POS).

• GP Pharm has scheduled a discussion with EMEA in QII’2007. The outcome of this meeting will determine the trial design for Phase II/III.

Note: Scenario probabilities do not add up to 100% due to rounding effects.

LaunchQIII'2010 QIV'2010

Submit: QII'2009 90% 72%QIV'2008

Start QIV'2007 80% Registration

10% 8%

Phase II/III

20% 20%

Sarcodoxome®

Liposomal doxorubicin - STS -

Phase II/III OK- GO TO Registration -

Phase II/III failed- STOP -

Approval

Non-approval


Derivation of patients eligible for treatment - STS

Sources:1. BSV population database2. American Cancer Society3. Cancer Research UK4. Weisberg et al, 20035. SEER fact sheets6. Assumption by Bioscience Valuation

2020 figures (USA, EU5)

Total populationUSA: 330 million [1]EU5: 302 million [1]

Patients receiving chemotherapy =patients eligible for Sarcodoxome®

Patients receiving chemotherapy =patients eligible for Sarcodoxome®

Patients with soft tissue sarcoma(incidence)

USA: 10,099EU5: 8,705

USA: 10,782EU5: 9,294

USA: 0.0031% [2]EU5: 0.0022% [3]

USA: 7,574EU5: 6,529

USA: 8,578EU5: 7,349

STS patients excluding GIST

Regional disease (prevalence)

75% [4](70% - 75% - 80%, Pert)

25% [5] (19% - 25% - 31%, Pert)

Adjusted for stage-specific 5-year survival rates [5]

Distant disease(prevalence)

15% [5](11% - 15% - 19%, Pert)

Adjusted for stage-specific 5-year survival rates [5]

USA: 2,772EU5: 2,390

95% [6](90% - 95% - 100%, Pert)

Sarcodoxome®


Project

Indication

Country USA France Germany Italy Spain UK

Patients receiving chemotherapy in 2020 / '000 10.782 1.956 2.666 1.862 1.317 1.493

Current MNF price per vial / EUR

# of vials per treatment cycle

# of treatment cycles per patient per year

Compliance rate

MNF price per year in 2020 / EUR 12,883 9,959 9,959 9,959 9,959 9,959

Final peak patient share (% of patients receiving chemotherapy) 35%

Sarcodoxome®

Soft tissue sarcoma

90%

2.66

4

1,040

Project

Indication

Country USA France Germany Italy Spain UK

Patients receiving chemotherapy in 2020 / '000 10.782 1.956 2.666 1.862 1.317 1.493

Current MNF price per vial / EUR

# of vials per treatment cycle

# of treatment cycles per patient per year

Compliance rate

MNF price per year in 2020 / EUR 12,883 9,959 9,959 9,959 9,959 9,959

Final peak patient share (% of patients receiving chemotherapy) 35%

Sarcodoxome®

Soft tissue sarcoma

90%

2.66

4

1,040

Pricing and patient share

Notes:1. See slide “Derivation of patients eligible for treatment”2. Prices per vial are based on the assumption of GP Pharm: EUR 1,200 - 1,400 (Uniform distribution) 20% deduction for calculation of MNF price3. GP Pharm assumption4. GP Pharm assumption5. Bioscience Valuation estimate6. For the USA Bioscience Valuation assumes an annual price increase of 2% from today onwards (BSV databases)7. Final peak patient share estimation by GP Pharm that takes into account potential future competition

2

3

4

5

6

1

Sarcodoxome®

7


Generic Name Synonyms Originator Licensee Pharmacology Statussarcoma

doxorubicin, Stealth CaelyxDOX-SLDoxildoxorubicin, Alza-2doxorubicin, Schering-PloughS-DOXSPI-49

Johnson & Johnson Schering-Plough DNA topoisomerase ATP hydrolysing inhibitor II

STA-4783 Synta Pharmaceuticals Heat shock protein 70 agonist II

ZIO-201 L-IPMlysine-isophosphoramide mustarZIO-202ZIO-203

Ziopharm DNA antagonistDNA synthesis inhibitor

II

doxorubicin, Supratek anthracycline, SupratekBiotransDoxSP-1049C

Supratek Pharma DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin citrate, Zeneus

D-99, TLCEvacetMyocetTLC D-99TLC-DOX99

Cephalon Sopherion Therapeutics

DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin, BioAlliance

BA-003 BioAlliance Pharma DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin, Nippon Kayaku

NK-911 Nippon Kayaku DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin, Celsion doxorubicin, DukeThermoDox

Celsion DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin, CytImmune

AuriClinCYT-31000

CytImmune Sciences DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin, Ambrilia TVT-Dox Ambrilia Biopharma DNA topoisomerase ATP hydrolysing inhibitorAngiogenesis inhibitor

n.k.

doxorubicin, TLC Lipo-Dox Taiwan Liposome Company

TTY Biopharm DNA topoisomerase ATP hydrolysing inhibitor n.k.

Generic Name Synonyms Originator Licensee Pharmacology Statussarcoma

doxorubicin, Stealth CaelyxDOX-SLDoxildoxorubicin, Alza-2doxorubicin, Schering-PloughS-DOXSPI-49

Johnson & Johnson Schering-Plough DNA topoisomerase ATP hydrolysing inhibitor II

STA-4783 Synta Pharmaceuticals Heat shock protein 70 agonist II

ZIO-201 L-IPMlysine-isophosphoramide mustarZIO-202ZIO-203

Ziopharm DNA antagonistDNA synthesis inhibitor

II

doxorubicin, Supratek anthracycline, SupratekBiotransDoxSP-1049C

Supratek Pharma DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin citrate, Zeneus

D-99, TLCEvacetMyocetTLC D-99TLC-DOX99

Cephalon Sopherion Therapeutics

DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin, BioAlliance

BA-003 BioAlliance Pharma DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin, Nippon Kayaku

NK-911 Nippon Kayaku DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin, Celsion doxorubicin, DukeThermoDox

Celsion DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin, CytImmune

AuriClinCYT-31000

CytImmune Sciences DNA topoisomerase ATP hydrolysing inhibitor n.k.

doxorubicin, Ambrilia TVT-Dox Ambrilia Biopharma DNA topoisomerase ATP hydrolysing inhibitorAngiogenesis inhibitor

n.k.

doxorubicin, TLC Lipo-Dox Taiwan Liposome Company

TTY Biopharm DNA topoisomerase ATP hydrolysing inhibitor n.k.

Competition - pipeline drugs for STS

Sources: PJB Pharmaprojects, April 2007Adis R&D Insight, April 2007

• The list below includes only those products in development that may have a moderate impact on the final patient share of Sarcodoxome®.

Sarcodoxome®

* n.k. = development for STS is not mentioned

*

*

***

***

• For most of the doxorubicin-based products no specific information regarding STS is available. To account for their potential impact, Bioscience Valuation has rated them “moderate” and assumed that they are in preclinical development.


Patient penetration

• Bioscience Valuation expects a market uptake with a TTP (time-to-peak) of 5 years because Sarcodoxome® will predominantly be marketed to clinical oncologists who usually adopt innovations fast.

• Patent expiry of Sarcodoxome® is assumed for 2020. GP Pharm assumes that Sarcodoxome®’s patient share will decline 5% annually from the year of patent expiry.

Sarcodoxome®

Patient penetration

0%

20%

40%

60%

80%

100%

120%

2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024

Year

% o

f po

tent

ial p

eak

pene

trat

ion

Patient penetration

0%

20%

40%

60%

80%

100%

120%

2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024

Year

% o

f po

tent

ial p

eak

pene

trat

ion


Commercial costs - promotional & sales force costs

• Phase IV costs make an additional 3% of peak sales in years 1 to 3.

Source: BSV benchmarks

• The costs per sales representative are assumed as indicated in the adjoining table.

• Example: one FTE targeting oncology specialists in the EU5 costs EUR 150,000 per year.

• Sales force costs do not include promotional efforts.

Sales force costs

Determination of promotional costs in the absence of detailed marketing plans

• Promotional costs (excluding Phase IV costs, excluding sales force costs) are estimated as percentage of peak sales.

Sales force cost Oncology Sales Force

Cost per FTE (EUR) USA 200,000

EU5 150,000

Sales force cost Oncology Sales Force

Cost per FTE (EUR) USA 200,000

EU5 150,000

Sarcodoxome®

International Promotion

Year relative to launch -1 0 1 2 3 4 5 6 … until patent expiry

% of peak sales 2% 4% 8% 8% 8% 4% 4% 4%

International Promotion

Year relative to launch -1 0 1 2 3 4 5 6 … until patent expiry

% of peak sales 2% 4% 8% 8% 8% 4% 4% 4%


Commercial costs - sales representatives per territory

• Bioscience Valuation assumes that Sarcodoxome® will be marketed primarily to clinical oncologists.

• To reflect pre-launch recruitment and training of sales representatives we assume that 30% of launch year costs are incurred in the year before.

Sarcodoxome®

Sarcodoxome (USA) (coverage: specialised hospitals) PatentExpiry

Year 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020

Sales reps targeting hospitals 15 15 15 15 15 11 6 6 6 6 6

Sarcodoxome (EU5) (coverage: specialised hospitals) PatentExpiry

Year 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020

Sales reps targeting hospitals 10 10 10 10 10 7 4 4 4 4 4

Source: BSV benchmarks


• Target markets: USA, EU5 (France, Germany, Italy, Spain, UK)

• Launch: 2010

• Patent expiry: 2020

• G&A costs: 5% of sales

• COGS: EUR 39 per vial (= EUR 415 per patient)

• Tax rate: 30%

• Discount rate: 25% until 200815% from 2009 onwards

• R&D costs: (all in EUR million)Phase II/III: 6.20CMC 0.18Approval: 0.06Internal costs: 1.29

Further assumptions for the project model - Sarcodoxome®

Total R&D costs:EUR 7.73 million

Sources:GP Pharm

Sarcodoxome®


Sarcodoxome®

-Results

Sarcodoxome®


2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027

USA 2 6 14 30 37 42 43 43 44 44 42 40 38 37 35 34 32 31

EU5 1 4 9 20 24 26 26 25 25 24 23 21 20 18 17 16 15 14

All countries 3 10 23 50 61 68 68 69 69 68 65 61 58 55 52 50 47 45

Sales forecast /EUR million

Sales forecast Sarcodoxome® for STS

0

10

20

30

40

50

60

70

80

2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027

Year

Sa

les

/ EU

R m

illio

n

Total

USA

EU5

Sales forecast Sarcodoxome® for STS

0

10

20

30

40

50

60

70

80

2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027

Year

Sa

les

/ EU

R m

illio

n

Total

USA

EU5

Sales forecast

• Based on an appealing target profile and EU orphan drug status (resulting in a comparably high patient share) peak sales may reach EUR 70 million in the niche indication soft tissue sarcoma (STS).

Sarcodoxome®

Note: Sales per region might not add up sales for all countries due to rounding effects.


USA + EU5 Expected Project NPV = EUR 64 million

Scenario Probability Scen. NPV Exp. Scen. NPV

1 72% 92,856 66,857 Launch

2 8% -17,582 -1,407 Non-approval

3 20% -7,885 -1,577 Failure after Phase II/III

Sum = 63,873(NPV values are in EUR thousands)

USA + EU5 Expected Project NPV = EUR 64 million

Scenario Probability Scen. NPV Exp. Scen. NPV

1 72% 92,856 66,857 Launch

2 8% -17,582 -1,407 Non-approval

3 20% -7,885 -1,577 Failure after Phase II/III

Sum = 63,873(NPV values are in EUR thousands)

NPV results Sarcodoxome®

Note: total costs = R&D costs + commercial costs

• The expected project NPV for Sarcodoxome® is EUR 64 million.

• The total cost per milestone include R&D cost as well as marketing & sales force cost. The total investment of EUR 14.1 million during the approval process consists of EUR 0,1 million for the regulatory / R&D effort and EUR 14.0 million for all pre-lunch marketing measures as well as recruitment and training of sales forces.

• Based on current assumptions the value of Sarcodoxome® at launch (i.e. after approval) would be EUR 166 million.

MilestoneTotal cost per

milestone(EUR million)

R&D cost per milestone

(EUR million)

Launch probability

Value(EUR million)

Current 72% 64

Phase II/III 9.2 7.8 90% 103

Approval 14.1 0.1 100% 166

MilestoneTotal cost per

milestone(EUR million)

R&D cost per milestone

(EUR million)

Launch probability

Value(EUR million)

Current 72% 64

Phase II/III 9.2 7.8 90% 103

Approval 14.1 0.1 100% 166

Biotecnología

Documents

Transcript of Biotecnología