EXCLUSIVE SYNTHESIS

TOLL MANUFACTURING

CUSTOMER SERVICE

INTERACTIVE PROJECTMANAGEMENT

CUSTOM SYNTHESIS& API CONTRACT MANUFACTURING

TOLL MANUFACTURING

• Pre-registered or marketed compounds• Technical transfer of existing process and analytical methods

EXCLUSIVE SYNTHESIS

• Molecules under clinical development: - From phase I to launch• Process Development offer for alternative synthetic route implementation: - Chemical and biotechnological development - Analytical development - Physical quality studies - Clinical supplies

PILOT PLANT PRODUCTION FROM TECHNICAL / ENGINEERING RUNS TO CLINICAL SUPPLIES

- Process Engineering and scale-up - Process safety

COMMERCIAL SUPPLY AT INDUSTRIAL SCALE

QUALITY & REGULATORY SUPPORT

CUSTOM SYNTHESIS & API CONTRACT MANUFACTURING UNDER cGMPFOR APIs OR MULTI-STEP INTERMEDIATES

Within the Industrial Affairs Division of Sanofi , CEPiA is an organization fully dedicated to third party activities. One of the key activities of CEPiA is to offer a broad range of innovative solutions including:• Intermediates and Active Pharmaceutical Ingredients (APIs) supply• Custom Synthesis & API Contract Manufacturing• Pharma Contract Manufacturing

CEPiA

CEPiA AT A GLANCE• 200 CEPiA collaborators close to customers• More than 200 APIs on catalogue…• … sold in 80 countries• API & Pharmaceutical CMO Services• 30 % of Chemistry and Biotechnology industrial activities of Sanofi

CEPiA guarantees REACH compliance.

• Oligosaccharides• Peptides• Oligonucleotides• Corticosteroids and Hormones• Prostaglandins• Opiates and opioids• Highly Active Products (HAP) • Multi-step heterocyclic chemistry

CHEMISTRY

• Plasmids• Therapeutic proteins (Production / Extraction / Purifi cation) - Extractive proteins - Recombinant proteins• Monoclonal antibodies

BIOTECHNOLOGY

EXPERTISE FIELDS

PROJECT IMPLEMENTATION

MARKET EVALUATION

SANOFI INDUSTRIAL CAPABILITIES & CAPACITIES

CUSTOMER VISITCONFIDENTIAL DISCLOSURE AGREEMENT (CDA)INITIAL DISCUSSIONS

NON-BINDING OFFER (NBO)PROCESS DEVELOPMENT & COMMERCIAL SUPPLY

AGREEMENT(S)LETTER OF INTENTPURCHASE ORDER

DEVELOPMENT SERVICE AGREEMENTMANUFACTURING & SUPPLY AGREEMENT

INQUIRY MANAGEMENTTECHNICAL PACKAGEREQUEST FOR PROPOSAL (RFP)

PRE-FEASIBILITY STUDY

DEVELOPMENT PLANINDUSTRIAL STRATEGY

COMMERCIAL SUPPLY

TECHNICAL TRANSFERVALIDATION

INDUSTRIAL PRODUCTION

COMPREHENSIVE CUSTOMER SERVICE

• Process development and commercial API production• Fully integrated offer including Drug Product and packaging INTERACTIVE PROJECT MANAGEMENT

• Project team with all relevant functions• Effi cient activities coordination (planning optimization)• Regular follow-up meetings to master operational and strategic project management

COLLABORATION BASED ON RESPECT

• Confi dentiality and Intellectual Property• Project timelines• Environment ➜ sustainable development (NYSE)• Ethical Chart• Sarbane-Oxley compliance

PROACTIVE SCIENTIFIC & COMMERCIAL RELATIONSHIP

• Proposals for potential improvements• Flexibility and responsiveness to customers’ needs RELIABLE & LONG-TERM PARTNERSHIP

CEPiA OFFERS

TIMEFRAMERFP NBO CONTRACT SIGNING PRODUCTION START

CDA NEGOTIATION

1 WEEK

COMMERCIAL SUPPLYTECHNICAL TRANSFER

4 - 8 MONTHS

CONTRACT NEGOTIATION

2 – 4 MONTHS

PRE-FEASIBILITY STUDY

4-6 WEEKS

CUSTOM SYNTHESIS & API CONTRACT MANUFACTURING

EUROPE & ROW: CHEMISTRY

Yannick LE STANCyannick.lestanc@sanofi .comTel: + 33 1 55 71 26 38

SteroidsOpiatesHighly Active ProductsSmall molecules

OligosaccharidesPeptidesOligonucleotidesSmall molecules

Mourad SAADYmourad.saady@sanofi .comTel: + 33 1 55 71 20 81

EUROPE & ROW: BIOTECHNOLOGY

Arnaud MARTINarnaud.martin@sanofi .comTel: + 33 1 55 71 24 88

NORTH AMERICA

Bob HUANGbaoguo.huang@sanofi .comTel: + 1 908 981 6969

John FULMERjohn.fulmer@sanofi .comTel: + 1 908 981 4217

Alan BENSONalan.benson@sanofi .comTel: + 1 314 416 5156

Monoclonal antibodiesPlasmidsRecombinant proteins

Extractive proteinsBiocatalysisBiochemical derivatives

Patrick CASTETSpatrick.castets@sanofi .comTel: + 33 1 55 71 26 39

GLOBAL HEAD

Philippe CLAVELphilippe.clavel@sanofi .comTel: + 33 1 55 71 68 72

JAPAN

Hikaru OHSAWAhikaru.ohsawa@sanofi .comTel: + 81 3 6301 3450

Chiho TADERAchiho.tadera@sanofi .comTel: +81 3 6301 3450

SCIENTIFIC & BUSINESSINTELLIGENCE

France-Emmanuelle THOLEfrance.thole@sanofi .comTel: + 33 1 55 71 28 76

Screenings & EvaluationsProspection supportMarket studies

20, avenue Raymond Aron F-92165 Antony Cedex - France - Tel: +33 1 55 71 42 82Communication: catherine.ortet@sanofi .com | www.cepia-sanofi .com

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Ankleshwar

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Our core competency is process development in chemistry and biotechnology. This involves:• Development, scale-up of APIs and intermediates processes from route scouting, laboratory development to kilolab and pilot plant scale• Technology transfers of chemical and biotechnological processes to production• Optimizing commercial processes through continuous improvements• Respect of cost and timelines

CEPiA’s strengths are:• High quality standards: excellent track record with Health Authorities• Technical experts including Process Development and production sites• Patents and legal representatives• Quality Assurance and Regulatory Affairs support• A global purchasing policy for an optimized supply chain of solvents and raw materials• Security / reliability of supply: possibility of internal dual sourcing• Financial stability

FACILITIES AND TECHNOLOGIES

INDUSTRIAL NETWORK

SUSTAINABLE DEVELOPMENT

CHEMISTRY & BIOTECHNOLOGY

CHEMISTRY

BIOCHEMISTRY

BIOTECHNOLOGY

HEADQUARTERS

VERSATILITY OF EQUIPMENT

High quality standards: excellent

AND TECHNOLOGIES

AnkleshwarAnkleshwar

Our core competency is process Our core competency is process development in chemistry and development in chemistry and excellent

AND TECHNOLOGIES

CHEMISTRY

EUROPE FOCUS

Frankfurt

Ploërmel

Vertolaye

Mourenx

Elbeuf

Ujpest

LyonGaressio

Haverhill

Sisteron

Aramon

Vitry

Antony

Brindisi

CHEMISTRY· Multi-purpose equipment from pilot-scale to 20 m3

· Total volume reactor > 4 000 m3

· Hydrogenations (up to 200 bar, up to 18 m3)· Temperature range (-120 °C to 220 °C)· Reactors in stainless steel, glass-lined, hastelloy· Continuous reaction processes· High vacuum product distillations (rectifi cation/thin-fi lm)· Large scale chromatography (reverse phase/ion exchange)· Centrifuges, fi lter-dryers, stirred pressure fi lters· Finished processing of APIs (milling, micronization, clean room packaging) · Examples of hazardous chemicals handled at industrial scale: o NaN3 (azidation, tetrazole formation) o Methylating agents (CH3Cl up to 15 bar, (CH3)2SO4) o Strong organometallic bases (NaNH2, LiHMDS, BuLi) o Cyanides (NaCN, KCN) o Hydrazine (H2N-NH2) o In situ generated borane (BH3)

CHEMISTRY· Synthetic alternative route scouting· Laboratory initial screening· Scale-up from 10 mL to 20 L reactors· Process optimization· Defi nition of optimal operating procedures and critical

parameters· Preparation of impurities : full synthesis and / or isolation· Preparation of reference standards· Production support: o Process improvement o Troubleshooting

BIOTECHNOLOGY· Upstream process: o Fermenters from 10 to 200 m3

o Mammalian cell culture : 400 to 10 000 L o Plasmids: dedicated facility with 3 500 L reactor · Downstream process: o Biomass separation by membrane or centrifuge

technology o Excellence in viral safety : pre-viral / post viral zoning o Industrial chromatography (reverse phase, ion

exchange diameter, up to 1,4 m) o Filtration technologies: microfi ltration,

ultrafi ltration and nanofi ltration o Effi cient networking with Sanofi Fill and Finish

plants (integrated offer)

BIOTECHNOLOGY· Upstream: o Microbiology and molecular biology o Enzymology o Fermentation o Media Optimization o Cell engineering and cell culture · Downstream: o Extraction and fi ltrations o Refolding o Precipitation and crystallization

STATE-OF-THE-ART PRODUCTION FACILITIES

CHEMISTRY & BIOTECHNOLOGY DEVELOPMENT

PROCESS ENGINEERING· Thermal exchanges· Material transfers· Stirring· Scale-up and scale-down studies· Extraction and separation (Liquid/Liquid, Solid/Liquid)· Industrial chromatography· Modelization, equipment design and piloting· Process intensifi cation

PHYSICAL QUALITY· Crystallization design (polymorph and morphology screening)· Filtration and drying processes· Solid chain, milling, micronization· Powder properties determination

PROCESS SAFETY· Thermal analysis· Powder safety (granulometry, electrostatic properties explosion)· Runaway reactor

ENVIRONMENTAL DATA· Biodegradability of effl uent· Ecotoxicity· Support to waste water treatment plants

PILOT PLANT BATCHES· Technical batches (engineering, scale-up)· Clinical supply· Primary stability· Registration (DMF)

ANALYTICAL CAPABILITIES· Development and validation of analytical methods· Structural characterization· Impurity identifi cation, quantifi cation and tracking· Glycan mapping, peptide mapping, identifi cation of aggregates· Comparability studies· Purity analysis· Stability studies· Trace analysis (organic or inorganic)

QUALITY CONTROL· In-Process-Controls (IPCs)· Testing of raw materials & APIs· Testing of standards and reference materials· Cleaning verifi cation and validation

QUALITY ASSURANCE & REGULATORY SUPPORT

· cGMP compliance· Regulatory support for fi ling· Qualifi cation of suppliers· Release of materials

HIGHLY ACTIVE PRODUCTS

ISO 7 CLASSIFICATION

OUTSTANDING FACILITIES

OEB 5 COMPOUNDS

HIGHLY SKILLED TEAMS

CEPiA offers to customers to have their Highly Active Product (HAP) projects handled by the same ex-perts who developed and manu-facture the two marketed drugs: Docetaxel (Taxotere®) and Cabazi-taxel (Jevtana®)

We are committed to sharing our scientifi c knowledge and experience in pharmacology and toxicology to support your project.

Our internal team of experts in industrial hygiene can assess OEB* categorization for APIs and upstream intermediates only when necessary to minimize costs. We apply the OEB* index from 1 to 5 relative to the product toxicity. OEB* index corresponds to an OEL** range (see the following table).

Our high level of expertise acquired through solid and long lasting experience in handling cytotoxic compounds is strongly set on four principles:

*OEB: Occupational Exposure Brand**OEL: Occupational Exposure Level

OEB* OEL** Range (µg/m3)

OEB 1 1 000 - 5 000

OEB 2 100 - 1 000

OEB 3 10 - 100

OEB 4 1 - 10

OEB 5 < 1

• Extensive knowledge in Chemistry

• State-of-the-art facilities

• Highly trained team

• Environment, Health and Safety experts

Our facilities for highly active compounds manufacturing are located near Paris (France), operated under cGMP procedures and are governed by Sanofi Quality Control. On the same site, two production units are suitable for technical transfer and process development, small scale production and large industrial scale manufacturing. These two units are operated in ISO 7 classifi cation for OEB 4 and OEB 5 compounds and are regularly inspected by Health Authorities, including FDA,EMA & PMDA.

All the production lines are equipped with the latest technologies in isolators, glove boxes, vessels and drying equipment. Machinery is fully or partially segregated with air control systems satisfying the most stringent requirements for product and personnel protection.

Our volume range is 5 - 1 000 L reactors in stainless steel, hastelloy and glass-lined for a total of 39 reactors (total volume of 10 m3). Upon request, we provide milling and micronization services for HAP in ISO 7 room. The total staff is nearly 80, working in one or two shifts. Highly trained personnel are recognized for their ability to work meticulously and safely in contained environment.

CONTACTS

HAPEurope: yannick.lestanc@sanofi .comUSA: alan.benson@sanofi .comJapan: hikaru.ohsawa@sanofi .com

HIGHLY SKILLED TEAMS

20, avenue Raymond Aron F-92165 Antony Cedex - France - Tel: +33 1 55 71 42 82Communication: catherine.ortet@sanofi .com | www.cepia-sanofi .com

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CHEMISTRY & BIOTECHNOLOGY

20, avenue Raymond Aron F-92165 Antony Cedex - France - Tel: +33 1 55 71 42 82Communication: catherine.ortet@sanofi .com | www.cepia-sanofi .com

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OLIGOSACCHARIDES20 YEARS EXPERTISE

200 CHEMICAL STEPS DEVELOPED

SYNTHETIC HEPARINOÏDS

WORLDWIDE LEADER

Sanofi has been involved in oligo-saccharide chemistry since the 90’s and is recognized as a world-wide leader in API manufacturing in this fi eld.Amongst this family of very active anti-thrombotic derivatives, Sanofi developed and marketed semi-synthetic or fully synthetic hepari-noïds. For the fully synthetic oligosac-charides, Sanofi has developed complex molecules which manu-facture requires a high number of chemical steps (up to 80 chemical steps).

For the projects, we develop a sy-nergetic approach using a common building-blocks strategy based on our worldwide industrial network.Main advantages:• Minimize the number of chemical intermediates• Reduce lead time• Increase security of supply• Optimize cost of goods.

More than 200 chemical steps have been developed by our teams and more than 100 experts have been involved to ensure a high level of performance on this very specifi c chemistry being able to manage even at production scale:

• Activation of oligosaccharides throughout trichloroacetimidates, thioglycosides

• Coupling reactions (glycosylations): - stereoselective & stereospecifi c reactions - low temperature (down to -50 °C at production scale) - anhydrous conditions (water contents below 10 ppm)

• Orthogonal protection/deprotection strategy

• Specifi c expertises in: - azidation - hydrazine handling

In addition, our analytical department fully supports these development activities with:

• Chromatography techniques (HPLC, GC, IC, CE) with specifi c detection for molecules without UV absorption

• Mass spectrometry (Q-TOF, TOF, Ion-trap) and NMR (500 MHz and 300 MHz) to elucidate very complex chemical structures

CONTACTS

OLIGOSACCHARIDESEurope: mourad.saady@sanofi .comUSA: baoguo.huang@sanofi .comJapan: hikaru.ohsawa@sanofi .com

Laboratories for oligosaccharidesynthesis and analysis

• Kilolab facilities for production of small scale batches to support phase I to phase III clinical studies

• Kiloprep facilities for normal, reverse phase chromatography: Prochrom systems (50 to 300 mm)

• Pilot plant and production facilities: from 50 L to 6 000 L

• Ion exchange dedicated purifi cation facilities from grams to kilograms of APIs

TOOLS - FACILITIES

WORLDWIDE LEADER

20, avenue Raymond Aron F-92165 Antony Cedex - France - Tel: +33 1 55 71 42 82Communication: catherine.ortet@sanofi .com | www.cepia-sanofi .com

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PEPTIDES & OLIGONUCLEOTIDES

STATE-OF-THE-ART EQUIPMENT

SCIENTIFIC EXPERTISE

INNOVATIVE PLATFORM

LIQUID & SOLID PHASE CHEMISTRY

Our “TIDES” Platform is embedded in a unique state-of-the-art infrastruc-ture on one of the largest industrial chemistry & biotechnology sites in Frankfurt (Germany). CEPiA offers customized services (manufacturing and analytical) from clinical phase to submission and launch (grams scale up to kilo-grams quantities), including regula-tory support, as well as commercial supplies. On the same location, cGMP API manufacturing can be combined with Drug Product and Devices technologies.

Our facilities are regularly inspected by Health Authorities, including FDA, EMA and PMDA.

One of our current development is the oligonucleotide-peptide conju-gation.

• Liquid phase peptide synthesis and synthesis of intermediates (50 - 600 L)

• Solid phase peptide synthesis (10 - 280 L)

PEPTIDE DEVELOPMENT AND PRODUCTION

ProcessDevelopment

Pilot Synthesizer10-80 L

Clinical TrialQuantities

CommercialBatches

Chromatography300/350 mm

columns (lEx, RP)

Lyophilizers(10 Kg + 40 Kg ice)

Production Plant

Production Plant

Synthesizer 280 L

Production Plant

Chromatographyup to 1 400 mm

columns (lEx, RP)in industrial network

Lyophilizer(100 Kg ice)

Synthesis

Purifi cation

Isolation

Cleavage & Precipitaion

Solid Support/Resin

Resin + Peptide

Chromatography 1

Chromatography 2

Vacuum - Distillation

Lyophilization

Crude Peptide

Pure Peptide

Full analytical service: - Structural characterization - Development of analytical methods - QC testing for batch release - Full scope of analytical studies needed for fi ling

Solvent supply lines, storage areas and waste management are designed according to the latest European standards.

Through Sanofi ’s 25 years experience in the fi eld of oligonucleotides, CEPiA can provide different classes of Oligonucleotides such as DNA, 2’-O-Modifi ed, phosphorothioate derivatives.

Chromatographyup to 1 400 mm

in industrial network

Production Plant

Pilot Synthetizer up to 600 mmoles

scale of crude Oligonucleotide (“Oligo Process”

with 12 independent amidite ports)

LyophilizerIsolation

Purifi cation

Desalting &Concentration

Synthesis

Deprotection & Cleavage

Chromatography

Solid Support

Ultra-fi ltration

Oligonucleotide/Support

OligonucleotideSolution

Lyophilization

PureOligonucleotide

OLIGONUCLEOTIDE DEVELOPMENT AND PRODUCTION

CONTACTS

TIDESEurope: mourad.saady@sanofi .comUSA: Peptides alan.benson@sanofi .com Oligonucleotides baoguo.huang@sanofi .com Japan: hikaru.ohsawa@sanofi .com

INNOVATIVE PLATFORM

20, avenue Raymond Aron F-92165 Antony Cedex - France - Tel: +33 1 55 71 42 82Communication: catherine.ortet@sanofi .com | www.cepia-sanofi .com

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VIRAL VECTORSFOR GENE THERAPY AND VACCINES APPLICATIONS

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Sanofi has been a pionneer in the fi eld of Gene therapy in the 80s’ through Gencell organization developping Viral Vectors. Sanofi through its vaccines division has a successfull history in virus production with launch of a large number of vaccines based on viruses.CEPiA offers its services to produce Viral Vectors through its Sanofi Pasteur and Genzyme divisions.

VIRAL VECTORS

MERIAL

SANOFI PASTEUR

GENE THERAPY

THERAPEUTIC VACCINES

GENCELL 1998

GENZYME

Sanofi team, with 20 years of experience, is a leading com-pany in the production of viral vaccines (wild type or recom-binant virus) and viral vectors.CEPiA offers a broad range of services such as, cell and virus banking, process scale up to commercial scale scale manufacturing with various technologies (static culture, dynamic culture in single use bioreactors up to 1000 L).Through Sanofi industrial network, CEPiA can provide Fill & Finish services.

Lyon (France) a cluster of excellence to support external partners’ projects:• Experts in Virology for vector

optimization• Upstream and downstream process

excellence based on mammalian cell culture (suspension and adherent cell line on microcarriers), viral culture for vaccines production

• Engineering teams worldwide,working in close cooperation with equipment manufacturers

• Global knowledge managementto implement the most recent technical innovations

• Analytical and regulatory services• Fill & Finish facilities

CONTACTS

Viral VectorsEurope: arnaud.martin@sanofi .comUSA: john.fulmer@sanofi .comJapan: hikaru.ohsawa@sanofi .com

Broad range of products upon request :- Adenovirus- Recombinant adeno-associated virus (rAAV)- Sendaï virus- Modifi ed Ankara virus (MVA)- Lentivirus The teams, located in Lyon (France), have a signifi cant track record and have a successfull and diversifi ed experience in process and analytical transfers.Sanofi Pasteur and Genzyme collaborate to established a seamless project management.

Clinical batches can be provided from Sanofi Pasteur’s site located in Marcy L’Etoile (Lyon, France).For the production of commercial batches, a new industrial platform in Lyon (France) combining expertise from Sanofi Pasteur and Genzyme will be operational in 2015.

20, avenue Raymond Aron F-92165 Antony Cedex - France - Tel: +33 1 55 71 42 82Communication: catherine.ortet@sanofi .com | www.cepia-sanofi .com

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In a worldwide competitive and fast evolving environment, start-up pharmaceutical and biotech companies need fl exibility. Takingadvantage of historical success, CEPiA offers to its customers a fl exible and innovative solution to achieve success with their bio-logics projects, from development to commercialization.

CHIMERIZATION AND HUMANIZATION

MAbLaunch™

PERFUSION & FED-BATCHES

mAbs

CHO CELLS

INTERLEUKINS

BIOPHARMACEUTICAL PRODUCTS (2 OF 2)MAMMALIAN CELL CULTURE

Sanofi offers biomanufacturing services from clinical phases to commercial scale:• Expression vector construction• mAb chimerization and humanization• Cell line development• Biosafety risk assessment done by viral experts• Strong analytical background with sophisticated glycosylated proteins• Full range of analytical and regulatory support• Fill & fi nish facilities to offer one-stop-shop

Development and production of monoclonal antibodies and therapeutic proteins from two facilities.

CAPI organization (Frankfurt, Germany) from early phaseto phase III:• 66 technical experts for development of mAbs processes and analytical for in-house and customers purpose• Perfusion and fed-batches• Disposable and stainless steel bioreactors from 20 L to 2 500 L• Purifi cation column from 20 cm to 60 cm• Signifi cant track records• Successful transfer of processes and analytical methods• Analytical expertise to characterize proteins and release cGMP batches

A FULLY INTEGRATED ORGANIZATION TO PRODUCEMONOCLONAL ANTIBODIES & THERAPEUTIC PROTEINSFROM MAMMALIAN CELL CULTURE

A FULLY INTEGRATED ORGANIZATION TO PRODUCEA FULLY INTEGRATED ORGANIZATION TO PRODUCEMONOCLONAL ANTIBODIES & THERAPEUTIC PROTEINSMONOCLONAL ANTIBODIES & THERAPEUTIC PROTEINSFROM MAMMALIAN CELL CULTURE

BioLaunch organization co-located with Process Development (Vitry-sur-Seine, France): from phase III to commercial batches• 60 scientists and technicians• recently built state-of-the-art facility dedicated to mammalian cells bioproduction• 3 modular stainless steel trains• 2 separate seed trains from 100 L up to 3 000 L• 1 bioreactor of 2500 L and 3 bioreactors of 10 000 L based on fed-batch processing• broad range of associated downstream process (DSP) to achieve purifi cation of mAbs

Additionally, LFB Biomanufacturing & Sanofi have combined their bioproduction capabilities to provide integrated CMO services for biopharmaceuticals (MAbLaunch™, see specifi c brochure).

CONTACTS

MAMMALIAN CELL CULTUREEurope: arnaud.martin@sanofi .comUSA: john.fulmer@sanofi .comJapan: hikaru.ohsawa@sanofi .com

VITRY-SUR-SEINE (FRANCE)

mAbs

20, avenue Raymond Aron F-92165 Antony Cedex - France - Tel: +33 1 55 71 42 82Communication: catherine.ortet@sanofi .com | www.cepia-sanofi .com

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FROM INSULIN AND GROWTH HORMONETO BIOPHARMACEUTICAL CMO SERVICE

FRAGMENTS OF ANTIBODIES (Fabs)

POLYCLONAL ANTIBODIES

PLASMIDS ANDDNA VACCINES

BACTERIA & YEASTS

ENZYMES

PROTEINS

BIOPHARMACEUTICAL PRODUCTS (1 OF 2)MICROORGANISM FERMENTATION & EXTRACTION

HOECHST1923 Production of extractive insulin1936 Crystallized insulin 1976 Production of semi-synthetic insulin

AVENTIS 1999 Recombinant insulin from E.Coli fermentation (Insuman®)2000 Launch of Lantus® 2004 Launch of Apidra®

SANOFI-AVENTIS 2005 Routine production of recombinant urate oxidase2009 Purifi cation of therapeutic proteins

SANOFI1984 Recombinant hGh through E.Coli fermentation

GENZYME 1994 Launch of Cerezyme®

2001 Launch of Fabrazyme®

2002 Launch of Aldurazyme®

2006 Launch of Myozyme®

From the 60’s, Sanofi has been a leader in the fi eld of large-scale fermentation with the productionof vitamins, antibiotics and steroids. In the 80’s, the production of recombinant proteins and enzymes has been a pillar of growth for the company.Fighting against Diabetes, Sanofi has become a leader in recombinant processing through its biosynthetic insulin business.Moreover, Sanofi has built a large library of microorganisms and non-natural enzymes, in order to have access to the optimized complex molecules.

Expertise available from 3 centers of excellence:Frankfurt (Germany): specialized in fermentation and downstream process (DSP)Aramon (France): specialized in DSP to process natural extracts, plants, and animal milkLyon-Gerland (France)-(former Genzyme plant): skills and capacities to process blood derivatives (site purifi es Thymoglobulin from blood cells)

Continuous process and cost improvement using latest innovation (combining stainless steel and disposable equipment)

A broad range of services to achieve your success: • Biosafety risk assessment done by viral experts• Fill & fi nish facilities to offer one-stop-shop (liquid and lyophilized vials, injectable syringes)

Our upstream expertise covers:• Strain building and optimization (molecular biology team in Frankfurt- Germany)• Master cell bank cGMP production and storage• High density fermentation up to 55 m3

• High throughput cell disruption techniques• Inclusion body technology (processing, refolding)

Our downstream expertise covers:• Isolation techniques of a broad range of solutes and solids: continuous centrifugation, fi ltration, drying• Process scale-up using in-house know-how and tools• Large scale low to high pressure

chromatographic techniques for the purifi cation of proteins (glycosylated, multimeric)

PRODUCTION AND PURIFICATION OF THERAPEUTIC PROTEINS AND ENZYMES:FERMENTATION / PLANT EXTRACTION / ANIMAL ORIGINPRODUCTION AND PURIFICATION OF THERAPEUTIC PROTEINS AND ENZYMES:FERMENTATION / PLANT EXTRACTION / ANIMAL ORIGINPRODUCTION AND PURIFICATION OF THERAPEUTIC PROTEINS AND ENZYMES:FERMENTATION / PLANT EXTRACTION / ANIMAL ORIGINPRODUCTION AND PURIFICATION OF THERAPEUTIC PROTEINS AND ENZYMES:FERMENTATION / PLANT EXTRACTION / ANIMAL ORIGINPRODUCTION AND PURIFICATION OF THERAPEUTIC PROTEINS AND ENZYMES:PRODUCTION AND PURIFICATION OF THERAPEUTIC PROTEINS AND ENZYMES:FERMENTATION / PLANT EXTRACTION / ANIMAL ORIGINFERMENTATION / PLANT EXTRACTION / ANIMAL ORIGINPRODUCTION AND PURIFICATION OF THERAPEUTIC PROTEINS AND ENZYMES:PRODUCTION AND PURIFICATION OF THERAPEUTIC PROTEINS AND ENZYMES:FERMENTATION / PLANT EXTRACTION / ANIMAL ORIGIN

THERAPEUTIC PLASMIDS& DNA VACCINES

Sanofi has an unique expertise with creation, productionand purifi cation of plasmids through in-house program.One compound completed international phase III studies:INDs and IMPDs submitted and drug substance validation completed.

State-of-the-art workshop located in Frankfurt (Germany)is equipped with several trains of fermentation up to3 500 L with associated downstream process (DSP).

Upstream process :• Cell banking: master cell bank, working cell bank• High cell density fermentation

Downstream process :• Specifi c equipment for continuous cell lysis• Expertise in the purifi cation of plasmids at large scale• Technology available for the affi nity chromatography of plasmids

Specifi c technology andplasmid design:• Sanofi patented pCOR technology• Batch size: 30 / 40 g• High number of copies• No antibiotic resistance gene• Insertion of multimer resolution gene

Example of a plasmiddeveloped in-house:• Double stranded circular DNA• Supercoiled form• Size: 1.5 million Dalton

CONTACTS

MICROORGANISM FERMENTATION & EXTRACTIONEurope: arnaud.martin@sanofi .com patrick.castets@sanofi .comUSA: john.fulmer@sanofi .comJapan: hikaru.ohsawa@sanofi .com

Contract manufacturingservices offer:• cGMP batches from preclinical phase to commercial scale• Transfer of customer’s process and analytical methods• Fill & fi nish facilities• Specifi c analytical expertise (to characterize and release material)

20, avenue Raymond Aron F-92165 Antony Cedex - France - Tel: +33 1 55 71 42 82Communication: catherine.ortet@sanofi .com | www.cepia-sanofi .com

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