Sartorius Stedim CellcaCustom Cell Line & Process Development for Pharmaceutical Purposes May 2017

Overview of Contents

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Cellca History

Overview: Cellca Technology Platform

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Products & Services

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Key Parameters: Why Cellca?

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5 Contact Information

Cellca History

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2012-2015

20152005-2010

2010-2012

• Founded by Dr. Cayli• Focus: R&D,

integrate molecular& cellular biologywith process know-how

• ProductDevelopment

• Building Infrastructure

• First technologytransfer

• Growing thecompany & customer base

• Completed 48 projects

• Improving theplatform & performance

• Growinginternationally asa part ofSartorius group

Overview: Cellca Technology Platform

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Host cellline

Expression Vector

UpstreamProcess Design

Media System

Host Cell Line: CHO DG44 growth in suspension, 18 h doubling time, long term stability

Expression Vector: DHFR selection system, low DHFR expression, S/MAR elements, optimal signal peptide

Media System: Optimized, chemically defined, free of animal components, proteins & peptones, high cell densities, viabilities & productivity

Upstream Process Design: robust, easy to scale, provenperformance in various bioreactor systems

Cellca

Cell Line Development

Process Transfer

GMP Production

Downstream Processing

Fill & Finish

Process Development

CMO/Client

Products & Services

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FEE FOR SERVICE

Our service is divided into individual work packages starting from DNA synthesis to RCB generation, stability studies, or process confirmation in lab-scale bioreactors.

TECHNOLOGY PLATFORM LICENSING

Technology transfer to enable in-house generation of high producing cell lines

MEDIA SUPPLY All parts of the media system are completely chemically defined and optimized for the different stages. They are commercially available.

Key Parameters: Why Cellca?

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Speed

Performance Customer Focus

Track Record

Scalability

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From DNA to RCB within 4-5 months.

No need for media and process development. Save up to 3 months by omitting scalability studies!

Speed

Vector Cloning Transfection and Pool Generation Single Cell Cloning Clone Evaluation RCB Preparation

From DNA to RCB in 4 to 5 months

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Scalability

Cellca technology platform was developed from scratch specifically for the industrial production

Focused development at Cellca lead to a process providing:

Direct and robust scale-up to production scale

No need for scalability studies

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Scalability

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Comparison VCC, Viability, Product conc. - 25-mL, 5-L & 1000-L

SF 25-mL VCC BIR 5-L VCCSUB 1000-L Xcellerex VCC SF 25-mL ViabilityBIR 5-L Viability SUB 1000-L Xcellerex ViabilitySF 25-mL Product BIR 5-L ProductSUB 1000-L Xcellerex Product

VCCViability

Viability

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Performance: Titer

Efficient cost reduction by achieving steadily productivities of 3g/L or more

Cost reduced by 50% by omitting media and process optimization

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Cost of Goods €/gClone distribution Cellca*95%; ≥ 3 g/L

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Performance: Quality

Targeted modification of quality attributes (e.g. glycosylation pattern)

Application for biosimilars

Scalability of modifications

Cellca Track Record (March 2016)

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>40 cell lines built to date Small, Medium and

Big Pharma US, EU, Asia

Customers 60% returning

customers

95% express 3 g/L or more

Monoclonal Antibodies (IgG1, IgG4, IgG2)

Fusion Proteins

Fab-related products

Bispecifics

Biosimilars

Applications:

NBE

Biosimilar projects

Replacement E. coli

Productivity Improvement

Track Record

2 g/L 3 g/L 4 g/L 5 g/L 6 g/L

Pre-clinic &Phase 1 4 21 9 4 2

Phase 2 1 1 - - 1

Phase 3 1 - - - -

Market Approval - - - - -

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DetailedDiscussions

F2F, TCs

Agreement by both

sides

Final proposal SLA

PROJECT:Committed project team & close contactwith Customer Order Manager:

Renate WestnerAlexander PietschmannHeike Mayer (Head of Team)

Customer Focus

Kick Off Data Packages Regular TCs

Scopechangespossible

Final report

PROPOSAL:Direct service and support byProduct Management Team:

Adelheid BurkhardtDr. Lucia Rieger

Benefits of Cellca Technology Platform

SPEED From DNA to high-titre RCB in 4-6 months. Save up to 3 monthsby omitting the need for scalability studies.

SCALABILITY Processes can be easily transferred and scaled-up to a range of bioreactors up to 1000L.

PERFORMANCE 95 % of our developed cell lines deliver protein titres exceeding 3 g/Lin a 12-14 day standard fed-batch process.

TRACK RECORD More than 40 successfully completed projects using the CellcaCHO Expression Platform.

CUSTOMER FOCUS Committed project teams and dedicated client manager’s make it their purpose to deliver service excellence and meet our clients requirements.

For more information on Sartorius Stedim Cellca’sCell Line Development services:

Contact us at www.biooutsource.com/contact-us/