LFB GROUP & SANOFI combine their bioproduction capabilities to provide integrated CMO services for biopharmaceuticals

MAbLaunchTM is a joint bioproduction platform combining LFB BIOMAnUFACTURInG (LFB Group) and BioLaunch (Sanofi) capabilities in the field of contract development and manufacturing services. The platform is supported by a collaboration agreement between Sanofi* and the LFB Group** to capitalize on the use of their respective industrial capacities and to provide the widest range of CMO services to customers in the most flexible manner.

MAbLaunchTM has developed considerable expertise in process development and manufacturing of monoclonal antibodies and recombinant proteins using mammalian cell technology.

The MAbLaunchTM offer starts with cell line development, going through process development and scale up and continuing into manufacturing of clinical and commercial batches. *through its subsidiary Sanofi Chimie

**through its subsidiary LFB BIOTECHnOLOGIESGMP production facilities:

• USP: 6 independent bioproduction lines with the following bioreactor capacities:

> 1x 300L (stainless steel bioreactor) > 1x 1,000L (disposable bioreactor) > 1x 2,000L (disposable bioreactor;

available soon > 3x 10,000L (stainless steel

bioreactors)

• Industrial chromatography systems

• Ultrafiltration/Diafiltration systems

• Viral inactivation/Nanofiltration

• Fill and finish facilities: > Pre-filled syringes from 0.5mL to 20mL > Cartridges from 1.7mL to 3.2mL > Vials from 2mL to 150mL > Lyophilized vials from 2mL to 20mL > Dosing system: time/pressure or

peristaltic pump

• Inspection: automated or semi-automated

Pilot facilities:Process development, pilot production and scale-up

• Bioengineering laboratory

• Mammalian cell line development platforms ( CHO and YB2/0 - EMABling® )

• Quality Control laboratory

• Roller bottle systems

• Spinners

• 25L Wave system

• 40L stainless steel bioreactor

• 50L & 200L disposable bioreactors

• Chromatography systems

• Virus inactivation and nanofiltration

• Filtration, ultrafiltration

• Analytical systems

Contract Biomanufacturing Services offer

Service Discovery Pre-clinical development

Clinical development Registration Commercialization

Pro

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Cell line development

Expression vector construction

MAb chimerization and humanization

Vector transfection and transient expression

Stable cell line generation and clone selection

EMABling® technology (see details on the right page )

Cell banking

Process development and scale-up

Cell culture Process development - Media optimization, yield improvement

downstream Process development

Viral clearance validation

Manufacturing of non-GMP batches up to 200L

Analytical development stability studies - QC testing

Manufacturing of clinical and commercial

batches

GMP master and working cell bank production

Manufacturing of GMP batches at 300L and 1,000L scale

Manufacturing of GMP batches at 10,000L scale

Galenic form development

Fill and finish vials, pre-filled syringes, freeze-dried vials, cartridges

Stability studies

Clinical packing

Contract Biomanufacturing Services offer

CeLL Line deveLOPMenT

MAbLaunchTM is able to offer bioproduction services using the client’s own cell line, or through a specific cell line development program, to express the client’s recombinant protein, using proprietary or non-proprietary cell expression systems.

The different steps may include molecular and cellular engineering to create a chimeric or humanized monoclonal antibody by vector construction, gene transfection and cell line development in order to establish a stable cell line.

neW! eMABling® technologyEMABling® is a technology developed by the LFB Group to produce highy active recombinant monoclonal antibodies using the YB2/0 cell line. These antibodies display an enhanced antibody-dependent cellular cytotoxicity (AdCC) activity due to an improved glycosylation profile. LFB’s research in this area has been based on the study of structure-function relationships for monoclonal antibodies and critical impact of post-translational modifications to their functional activity (role of glycans). Combined with specifically optimized expression vectors / CD medium and a powerful CLD process (including the use ClonePix-FL™ cloning robot), the EMABling® platform leads to gram-per-liter producing clones.

Customers now can access to the EMABling® platform to produce their own recombinant high-AdCC mAbs.

PrOCeSS deveLOPMenT And SCALe-uP

Process development and scale-up are essential to obtain a competitive commercial product. To tackle this important issue, MAbLaunchTM’s services cover adaptation of cell culture to serum-free media and/or media optimization for yield improvement.Upstream and downstream process optimizations are executed in state-of-the-art facilities. MAbLaunchTM’s technological options include static or stirred vessels, hollow-fiber bioreactors or disposable bioreactors. Our in-house scientists and our network of experts will facilitate the development of optimum cell culture conditions for each cell line. Our engineering staff have vast experience and the technical knowledge necessary to select the best chromatography and filtration systems, most appropriate buffers to establish optimal purification processes and viral clearance methods. MAbLaunchTM has a proven track record in tackling a number of challenging processes and scale-up, resulting in successful production of many antibodies and recombinant proteins.

MAnuFACTurinG OF CLiniCAL And COMMerCiAL BATCheS

With its versatile range of production technologies, MAbLaunchTM can undertake GMP cell banking and production of biopharmaceuticals for Phase I to Phase III clinical trials and small to large-scale commercial supplies to meet the specific needs of our customers.

In conjunction with these drug substance manufacturing capabilities, MAbLaunchTM (via the international network of Sanofi facilities) is able to offer access to significant fill & finish capacities for various finished dosage forms: • pre-filled syringes • liquid vials • lyophilized vials • cartridges

From state-of-the-art facilities, MabLaunchTM will be in a position to supply clinical and commercial products on a worldwide basis.

According to customer needs, associated services may range from standard transfer activities (scaling-up, analytical transfer, stability studies…) to specific support on technical issues, such as dosage form switch or compatibility studies, by experienced industrial and pharmaceutical development teams.

Program management and regulatory supportMAbLaunchTM understands the need to be at the forefront of developments in the field of Quality Assurance and Regulatory Affairs as well as the importance of transferring this information to its clients. MAbLaunchTM has access to the expertise and experience of the Sanofi and LFB teams, in Quality Control, Quality Assurance, Regulatory and Program Management. Our quality systems are dedicated to providing high-value products and services which enable our customers to conduct a project with confidence.

Each project is managed by a dedicated, experienced and multidisciplinary team who works in close collaboration with each customer to ensure that milestones are reached and that cost and timeline targets are met.

Key benefits : The advantages of large pharma combined with flexible CMO services• Comprehensive and global offer of services for protein-based biopharmaceuticals, from

mammalian cell line development to optimization of cell culture conditions and process development at small scale to preclinical, clinical and commercial manufacturing of drug substance and drug product

• An integrated, dual platform approach, which is fully adaptable to customer needs, offering the most suitable solution for each project, from small to large production quantities

• Extensive experience in evaluation, optimization and scale-up; avoiding unnecessary costs and delays in development

• Successful production track records for pre-clinical, clinical and commercial supply to biopharmaceutical companies

• Seamless integration: unified project management and quality assurance systems

• Thorough regulatory and QA support, including full documentation and controls at all steps of development and manufacturing

• Optimized entry cost and long-term cost effectiveness management

MAbLaunchTM is your CMO Partner for biologics

tobias.metzenthin@sanofi.com

roger.kriegl@sanofi.com

Tobias METZENTHIN

Roger KRIEGL