Therapeutic mRNA Production Services from Sequence to IND

An integrated service, featuring an up to 300 L scale fermenter, ensures efficient mRNA transcription, purification, and state-of-the-art mRNA-LNP production with expertise and excellence in quality system. This platform covers all critical CMC processes, achieving a timeline of 8 months from DNA to IND filing.

Services for mRNA Products

Advancing mRNA Therapeutics and Vaccines from Sequence to IND

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WuXi Biologics offers extensive development capabilities and GMP manufacturing capacity for mRNA therapeutics and vaccines. Our expert and highly-trained team provides end-to-end services from early-stage development through to initial plasmid DNA manufacturing and on to drug substance (DS) and drug product (DP) GMP production. Our GMP services include a manufacturing facility with up to 300L scale fermenter for plasmid DNA production and 50L volume vessels and purification equipment for mRNA transcription and purification. In addition, state-of-the-art mRNA-LNP production systems and robotic aseptic filling systems are available for DP manufacturing. Like all of our services, the foundation of our mRNA service platform is built upon remarkable in-house, single-source CMC development and manufacturing capabilities and expertise, execution excellence, and our world-class quality system. TIPS: We also provide rapid material generation and high-quality feasibility study services as standalone projects.

WuXi Biologics’ services for mRNA therapeutics and vaccines

Integrated, End-to-end Services from Sequence to IND

Plasmid DNA manufacturing

E. coli strain construction

Plasmid purification

Plasmid DNA

Fermentation

In vitro transcription (Co-capping or post-capping)

mRNA transcription and purification

Key services include: Sequence optimization MCB/WCB creation and testing Process development:

Plasmid DNA linearized template

mRNA purification

mRNA DS

mRNA-LNP formulation

Sterile filtration

LNP encapsulation

TFF

mRNA-LNP

Plasmid DNA: E. coli fermentation, cell lysis and purification mRNA: In Vitro Transcription (IVT) including co-capping or post-capping, purification LNP: encapsulation, UF/DF, fill/finish

DS & DP manufacturing

Stability

mRNA DS

mRNA-LNP

Release

Tech transfer and scale-up GMP manufacturing: DS and DP Comprehensive analytical development and QC testing capability Full CMC and regulatory support

WuXi Biologics services cover all critical CMC processes with a timeline of 8 months from DNA to IND filing.

8 months from DNA to IND filing

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Tox materials release

GMP pDNA release

DNA

GMP mRNA release

GMP mRNA-LNP DP release

Drug Substance

Our GMP services include a manufacturing facility with up to 300 L scale fermenter for plasmid DNA production and various volume vessels and purification equipment for mRNA transcription and purification.

For Sequence to Cell Bank

mRNA DS suite #1

Sequence synthesis

Sequence synthesis in 2-4 weeks; codon optimization

Vector construction

A matrix of vector backbones with different UTRs, polyA, restriction sites, etc.

Strain & clone screening

E. coli strain and clone screening for stable and high production of plasmid DNA

Bacterial cell banking

PD & GMP cell banking; cell bank release and testing

WuXi Biologics provides a matrix of vector backbones with different designs of promoters, UTRs, polyA, restriction sites, etc.

mRNA DS suite #2

mRNA Production Process

pDNA linearization

• Selection of restriction enzyme • Optimization of reagent concentration and reaction condition to ensure complete linearization

GMP plasmid DNA intermediate production • State-of-the-art GMP suites • Multiple single-use fermenters up to 300 L • Platform process with high yield

Purification of linearized pDNA

in vitro transcription

• With or without cap analogs • Optimization of reagent concentration and reaction conditions to achieve high yield of mRNA & complete digestion of pDNA template

GMP drug substance

mRNA recovery*

• One suite of pDNA linearization • One suite of mRNA synthesis • One purification suite for mRNA, with extensive utilization of advanced single use technology

Enzymatic capping*

• Optimization of reagent concentration and reaction conditions to achieve high capping efficiency and minimize enzyme cost

mRNA purification

*Not required for co-transciptional capping

Drug Product

Drug Product Manufacturing

Our DP offerings include state-of-the-art mRNA-LNP production systems as well as robotic aseptic filling systems.

• Two segregated Vanrx SA25 Robotic filling lines • Microfluidic and T-junction encapsulation processes • Aseptic formulation isolator • Single-use systems • Ready-to-use container-closure systems (vials and pre-filled syringes)

Drug Product Development

• Microfluidic and T-Junction mixing technologies • Formulation development, process development and technology transfer • Lyophilization cycle development • Stability, stress study, CCIT, clinical in-use study • 25 µL to 10 L scale (feasibility / pilot) • Extensive mRNA-LNP DP characterization techniques: particle size, PDI, encapsulation rate, potency, etc.

From sequence to LNP for all mRNA programs

Flexible dosage forms: liquid and frozen vials, freeze-dried vials and pre-filled syringes

Microfluidic Mixing Technology

Impingement Jets Mixing Technology

0.6 m 2 freeze-dryer equipped with AI software and nucleation control technology

Analytical Science and Quality Control

• Comprehensive analytical capabilities for full CMC packages that enable IND/BLA filings • Tox/Clinical lot DS/DP release and stability testing • Reference standard generation, qualification, characterization, storage, and life-time management • Analytical investigation/troubleshooting for GMP manufacturing related issues

Our dedicated team of highly trained and experienced analytical and QC professionals, allows us to offer: • Integrated labs that support diverse mRNA modalities • Methods development, transfer and qualification/validation • Product biochemical, biophysical, and biological characterization and comparability analysis

Identity

Purity

Impurity

Potency

Safety

pDNA supercoiled% A260/280 by UV absorbance

pDNA sequencing Restriction enzyme digestion

pDNA

Residual dsRNA Residual host cell protein by ELISA Residual host cell DNA Residual solvent Residual antibiotics Residual DNA template

S terility Bioburden Mycoplasma Endotoxin

RNA integrity and fragment Capping efficiency polyA tail length Encapsulation efficiency LNP size and zeta potential LNP morphology

In vitro GOI expression by Cell-based Assay(CBA)

RNA length RNA sequencing

RNA

RNA-LNP

Lipid identification

• Document management/ training • Deviation/CC/CAPA • Quality agreement management • Management review

• Batch release • Warehouse management • Product reception, storage, and distribution • Handling of abnormal and nonconforming materials and products • Supplier management

Quality Assurance System

• Internal audit • Batch release

• Sample management • Retained sample management • Reference standard management • Stability management • Environmental monitoring • Contamination and cross- contamination control strategy • DS/DP production technique transfer • Risk assessment of NPI • Clearance and changeover • Cleaning and disinfection

• Calibration and maintenance • Pest control • Validation management • Water system/HVAC

• Distribution and control of label

About WuXi Biologics

WuXi Biologics is a leading contract research, development and manufacturing organization (CRDMO) that provides end-to-end capabilities to healthcare organizations worldwide. With operations in China, the United States, Ireland, Germany, and Singapore, we enable our partners to effectively and efficiently bring biologics and vaccines to patients worldwide through our comprehensive and high-quality drug development model.

wuxibiologics.com | info@wuxibiologics.com The world’s leading global single-source platform from concept to commercialization.

5-12-2023

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