THE WORLD’S ONLY SINGLE-

SOURCE PLATFORM
FROM CONCEPT TO
COMMERCIALIZATION
State-of-the-art Technology Platforms to
Expedite Global Biologics Development
Chris Chen, CEO WuXi Biologics
ISPE Thailand
July 9 2018
Presentation Outline

 Biologics as Innovative Drugs to Treat Unmet Medical

Needs

 State-of-the-art Platforms at WuXi Biologics

 Successful Collaborations

Connecting Pharmaceutical Knowledge ispe.org 2

Biological Therapeutic Drug Market Share

The market share of biologics in top 100 selling drugs

2008 2016 2022

(30%) 49% 52%

Connecting Pharmaceutical Knowledge ispe.org 3

2016 Best Selling Drugs in Global: 7 out of Top 10 Biologics

Rank Drug Company Diseases 2016 Sales Type

($bn)
1 Adalimumab Abbvie RA 16.4 Biologics
2 Etanercept Amgen RA 9.3 Biologics
3 Sofosbuvir+ledipasvir Gilead HCV 9.1 Chemicals
4 Infliximab J&J RA 8.9 Biologics
5 Rituximab Roche Oncology 7.4 Biologics
6 Lenalidomide Celgene Oncology 7 Chemicals
7 bevacizumab Roche Oncology 6.9 Biologics
8 Trastuzumab Roche Oncology 6.9 Biologics
9 Insulin glargine Sanofi Diabetes 6.4 Biologics
10 Rivaroxaban Bayer Anticoagulant 5.6 Chemicals

Connecting Pharmaceutical Knowledge ispe.org 4

Global Antibody Therapeutics Market

1998 – 2015 Global Antibody Therapeutics Sales ($bn) and CAGR

100 1.8
91.63
158%
90 85.58 1.6

80 76.52
1.4
70 65.41
1.2
60 100% 57.44
53.36 1
50
42.82
0.8
40 67%
34.94
31.21 0.6
50% 50% 47%
30 46%
42%
22
33% 0.4
20 29% 15 23% 25%
10.3 14% 17%
10 8 12% 12% 0.2
4 8% 7%
1.2 2 3
0.8
0 0
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Sales CAGR

Connecting Pharmaceutical Knowledge ispe.org 5

New And Exciting Biologics Drug Targets Emerged

Science：Top of the Y2013 scientific breakthroughs

Connecting Pharmaceutical Knowledge ispe.org 6

Vision of WuXi AppTec Group
“Every drug can be made and every disease can be
treated” through building the open-access platform
with the most comprehensive capabilities and
technologies in the global healthcare industry.

Connecting Pharmaceutical Knowledge ispe.org 7

WuXi AppTec Group - An Open Enabling Platform with 6 Pillars

Small Molecule Cell Therapy Drug R&D and Biologics Genomics In-vitro and
Drug R&D and and Medical Device R&D and and Clinical
Manufacturing Gene Therapy Testing Manufacturing Data Platform Diagnostics

——————————————— WuXi AppTec—————————————— ——WuXi Biologics— ——WuXi NextCODE— ——WuXi Diagnostics—

（Stock code: 603259.SH / 2359.HK） （02269.HK）
）

22,000+ employees | 30+ sites | 3,000+ customers

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WuXi AppTec Group - Our Global Footprint U.S.
Boston MA Genomics &
Biologics
Manufacturing
China Plainsboro NJ DMPK and
Bioanalytical
Philadelphia PA Cell Therapy
Shanghai R&D Headquarters Manufacturing
San Diego CA Small Molecule R&D
Shanghai Clinical / Regulatory and Manufacturing
Austin TX Clinical
Shanghai Preclinical Drug Discovery Development Service

Changzhou Small Molecule R&D and Manufacturing St. Paul MN Medical Device
Testing
Jinshan Small Molecule Manufacturing Atlanta GA Medical Device and
Biologics Testing
Wuxi Biologics Manufacturing

Wuxi Cell and Gene Therapy R&D &

Ireland
Manufacturing
Dundalk Ireland Biologics Manufacturing
Suzhou Drug and Medical Device
Safety Evaluation
Nanjing DMPK and Bioanalytical Singapore
Qidong Small Molecule R&D
Singapore Singapore Biologics Manufacturing
Tianjin Chemistry and Drug Discovery

Chengdu Healthcare Industrial Park Germany

Wuhan Chemistry and Drug Discovery
Munich Germany Drug Discovery
Beijing Clinical / Regulatory

Guangzhou Program Management

Iceland
Shijiazhuang Clinical Development Service, R&D and Manufacturing Reykjavik Iceland Genomics

China U.S. Germany Iceland Israel Ireland Singapore Korea Japan U.K.
Connecting Pharmaceutical Knowledge ispe.org 9
WuXi AppTec Group - Entrusted by >3,500 Collaborative Partners

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WuXi Biologics

June 2017: $587M IPO

Biologics R&D and Manufacturing HKEX: 02269.HK
Top ten IPO on Hong Kong
Stock Exchange 2017
The only open-access biologics
technology platform in the world
Now a member of Hang
offering end-to-end solutions to Seng HK 35 Index and
empower organizations to discover, multiple other indexes
develop and manufacture biologics
from concept to commercial
manufacturing

4,150+ employees, 5 global sites, 220+ customers

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Our Mission and Business Model
Our Mission
To accelerate and TRANSFORM Biologics discovery, development and manufacturing
to benefit patients worldwide

Our “Follow the Molecule” Integrated Solution Model

Our customers’ demand for our services increases as their biologics advance through development and
ultimately to commercialization – our knowledge from working with clients in early stages, streamlines
future development and manufacturing activities and enables cost efficient solutions

Our Strong Proprietary Technology Platform

Biologics & ADC Manufacturing
Platform

Biologics Formulation Platform Biologics Discovery Platform

Biologics Characterization & Proprietary Cell Line Development

Testing Platform Platform

State-of-the-art Cell Culture Platform

Connecting Pharmaceutical Knowledge ispe.org 12

Our Global Footprint

Shijiazhuang
48,000L Wuxi • CMC development
111,000L • Pilot scale manufacture
Suzhou • Clinical and commercial mfg.
• Cell line characterization • Fed-batch and perfusion
• Viral clearance studies • Bioconjugation/ADC DS and DP
• DP FFF (vials & PFS / liquid & lyo)
Worcester, MA Dundalk, Ireland Chengdu
54,000L 48,000L
USA
4,500L

Shanghai
7,000L
Singapore • Discovery
4,500L • CMC development
280K+ • cGMP cell banking
176.5K • Pilot scale manufacture
• GMP DS clinical manufacture

Capacity in Progress (CIP) by Year 112K

(Liters) 52K Providing 280,000L of total bioreactor capacity

35K 42K
5K
and a global supply chain network across 4 countries

2012 2017 2018 2019 2020

Connecting 2021 2022
Pharmaceutical Knowledge ispe.org 13
All Services, One Central Location in China

Shanghai (multiple sites)

Wuxi city (multiple sites) Biologics Discovery
160km from Shanghai Biologics CMC Development
cGMP Cell Banking
Biologics CMC Development
Pilot Scale Manufacture
DS Pilot, Clinical & Commercial Manufacture
DS Clinical Manufacture
DP GMP Fill/Finish (vials & PFS)
Bioconjugation DS & DP Manufacture
All mAb, bispecific Ab and ADC
discovery, CMC and MFG
activities only 1-2 hrs. drive or
Suzhou less in China!
80km from Shanghai
Cell Line Characterization - Greatly streamlines DNA to IND
Viral Clearance Studies timeline
Connecting Pharmaceutical Knowledge ispe.org 14
Experience And Compliance Summary
The world’s ONLY single-source platform from concept to commercialization
Leadership and Team
Led by industry experts with 20+ years of experience across all functional areas
4,300+ employees and 355+ returnees
Track Record
220+ global clients including 13 of Top 20 Large Pharma & 22 of Top 50
205+ client molecules in development and/or GMP manufacture
Regulation
First in China to provide quality system that meets worldwide regulatory standard
Passed 125+ GMP audits from global clients
Approved by U.S. FDA and EMA for Commercial Production of TaiMed’s Trogarzo
IP Protection
We hold ourselves accountable for our clients’ IP

Connecting Pharmaceutical Knowledge ispe.org 15

 Experienced World-Class Leadership Team

Chris Chen, Ph.D. Weichang Zhou, Ph.D. JiJie Gu, Ph.D. Chiang Syin, Ph.D. Jian Dong, MBA Jing Li, M.D., Angus Turner, MBA
Chief Executive Officer Chief Technology Officer Chief Scientific Officer Chief Quality Officer Sr. Vice President Ph.D., MBA Vice President
Sr. Vice President Exec. Vice President Sr. Vice President Global Manufacturing Sr. Vice President Global BD & Alliance
Discovery Services Discovery Services Management

20 years’ experience 25+ years’ experience
Shanghai Kanda, Genzyme, PDL, Merck,
Celgen, AME, Eli Lilly, Fellow of the
Merck American Chemical
University of Society & American
Delaware (Ph.D.) Inst. for Medical and
Tsinghua University Biological Engineering,
(B.S.) University of
Hannover (Ph.D.)
20+ years’ experience 29 years’ experience 25+ years’ experience 20+ years’ 20+ years’
Biologics discovery, in FDA regulatory Unilab Bioscience, experience experience
preclinical and clinical review and GMP Celgen, Eli Novartis, Wyeth Lonza, Bayer,
development compliance Lilly,Shenzhen (Pfizer) AppTec
Harvard, Abbott, US FDA China Office, Kangtai,University of Peking University University of
AbbVie FDA CBER, CFDI of Webster (MBA) (M.D., Ph.D.), Yale Warwick (MBA),
Peking Union Medical CFDA (now NMPA) University (MBA) University of
College (Ph.D.), The Catholic Strathclyde (M.Sc.)
Editorial Board: mAbs University of America
(Ph.D.)

Scientific Advisory Board: James Larrick, M.D. and Ph.D. (Panorama), Ram Sasisekharan, Ph.D. (MIT),
David D. Ho, M.D. (Rockfeller), Wei-Shou Hu, Ph.D. (Univ. of Minnesota) and David Liu, Ph.D. (Harvard)

Connecting Pharmaceutical Knowledge ispe.org 16

Experienced World-Class Leadership Team

Jiexing (Jill) PK Tsai, Ph.D. Jie Chen, Ph.D. Xiaoya (Melinda) Xuelin (Michael) Xuejun (Sherry) Gang Huang, Zhuozhi Jimmy Li, Ph.D. Shiwen Lin, Ph.D.
Cai Vice President Vice President Ding, Ph.D. Gu, Ph.D. Gu, Ph.D. Ph.D. (George) Wang, Vice President Vice President
Vice President Quality (Training and CMC Management Vice President Vice President Vice President Vice President Head of MFG1,Drug Downstream Process
Integration) 20+ years’
Ph.D., MBA Substance Manufacturing
Cell and Protein Training Quality Control CMC Management Analytical Sciences Development
Vice President
Sciences 30+ years’ experience experience 20+ years’ experience 25+ years’ experience 20 years’ experience and Shanghai QC 18+ years’ biologics 25+ years’ biologics CMC
Discovery
20+ years’ in Bioprocess R & D Dyax, Shire Various CRO firms J&J, PPD BMS, Eli Lilly 20+ years’ experience development,scale- experience
20+ years’ experience
experience and managing Third Rutgers University University of University of Massachusetts Amgen, Sigma-Aldrich up&GMP manufacturing Biogen, Therion, BD
CancerVax/Micromet
Amgen, Abbott, party collaboration Wisconsin–Madison Nebraska-Lincoln Institute of Technology Purdue University experience Bioscience, Infimed,
Bayer; Peking
Millennium Merck (Ph.D.) (Ph.D.) (Ph.D.) (Ph.D.) Genentech, Tanox, Diversa Schering-Plough (now
University (Ph.D.),
Wesleyan University University of Minnesota University of Maryland, MSD), Vertex, Agenus
UC Berkeley (MBA)
(M.S.) (Ph.D.) Baltimore County (Ph.D.), Inc.
Tsinghua University Northeastern University
(Ph.D.)

Paul Liu, Ph.D. Brendan McGrath Keqiang (Peter) Liang Tang, Ph.D. DQ Wang, Ph.D. Gang Wang, Weijun (Wesley) Alan Wong, MBA Xuejian (Jerry)
Vice President Vice President Shen Vice President Vice President Ph.D. Wang, Ph.D. Vice President Xu, Ph.D.
Biodevelopment Head of Dundalk, Vice President Cell Culture Process Drug Products Vice President Vice President Head of MFG5&SJZ site Vice President
25+ years’ Ireland Site Head of MFG3, Development 25+ years’ Quality Process 30 years’ experience Quality Assurance
experience 15+ years’ experience Clinical Manufacturing 25+ years’ experience experience, Bayer, 20+ years’ Development Simcere, Regeneron, 25+ years’
Merck,Nektar, Livzon Organon, Schering- 25+ years’ experience in Biologics Adjunct professor at experience 25+ years’ Biogen,Wyeth (Pfizer), experience
Mabpharm, Plough and MSD Laurate Biopharm, development Purdue University CDE of CFDA, US experience Millennium, Le Moyne FDA, Genzyme,
Shanghai Henlius National University of DuPont Pharma, J&J, Bayer, Heska, Imperial and Peking University, FDA China Office, Amgen, Immunex, College (MBA), Wyeth (Pfizer)
University of Galway Ireland (B.S.), BMS College London Former president of FDA CBER & CDER BMS University of Rochester Northeastern
Delaware (Ph.D.) ACCA, lean six sigma New Mexico State McGill University CABS (Chinese Dartmouth Medical University of (B.S.) University (Ph.D.)
black belt University (M.S.) (Ph.D.) American School (Ph.D.) Georgia (Ph.D.)
BioPharmaceutical
Society) in the US
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Deep Pool of Talent

4,300+ people and expanding

VP and above 27
Exec. / Sr. Director ~75 ~9% returnees
Director/Assoc. Director ~210
Supervisor/Manager ~260
Scientist/Engineers/SGA ~3,600

~9% Ph.D. World’s largest

~50% M.S. CMC development
team among all
CDMOs Local CMC leader
& business contact
Connecting Pharmaceutical Knowledge ispe.org 18
Our Track Record

220+ Global clients, including 13 of the top 20 large pharma

Clients from US, China, EU, Japan, Korea, Singapore & Australia
Client molecules in development or manufacturing
205+ (97 in preclinical, 94 in Phase I/II, 13 in Phase III, 1 commercial)
120+ Cell-based assays developed
including 25 qualified for GMP
1 Client
BLA 290+ Stable cell lines developed
for GMP manufacturing
Approved
100+ IND-enabling worldwide
CMC projects completed
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2018 Pipeline Highlights

WuXiBody™ OMT Platform ADC Platform More……

Multiple-Platform Discovery Engines

• “Follow-the- Molecule”
strategy in full motion

57
47 (1) 7 Terminated
97 Preclinical
• Added 57 molecules into the
pipeline in 2018, total 205 in 7 33
68 Phase I 4
development and

205
manufacturing 22
2 26 Phase II 1
• 10 molecules transferred
from competitors including 1 1 5
13
phase III
13 Phase III 1

Commercial
1
Connecting Pharmaceutical Knowledge ispe.org 20
Note: All of the project No. were compared to 2017 Q4
1. The arrows in black are the projects newly added from outside; the arrows in blue are the projects progressing from earlier stage thanks to our Follow-the-molecule strategy; the dashed arrows are terminated projects.
Regulatory

• Innovative biologics co-development joint venture in China

• Innovative ADC mfg./development partnership in China

First • Batch release of cGMP DS & DP from China for US, EU, Australia
and Singapore
• cGMP biologics mfg. facility in China compliant with US, EU and
Chinese regulatory standards

Passed 125+ GMP audits from global clients

Passed 10 audits by EU Qualified Persons (QPs)

Approved by U.S. FDA and EMA for Commercial Production

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Extensive & Expanding Global Partnerships

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We Enabled the Success of Our Partners

2019/02/28
WuXi Biologics Congratulates Amicus on Receiving FDA Breakthrough Therapy Designation for AT-
GAA

2018/12/13
WuXi Biologics Congratulates Tychan on First-in-Class Monoclonal Antibody for Yellow Fever after
Record 7 Months of Development

2018/09/11
WuXi Biologics and Inhibrx Enter an Exclusive Partnership for GMP Manufacturing

2018/05/14
WuXi Biologics Congratulates Aravive Biologics on Achieving Proof-of-Mechanism for Novel Biologic
AVB-S6-500 within 20 Months from Cell Line Development

2018/03/07
WuXi Biologics Congratulates TaiMed on FDA Approval for Trogarzo

2018/01/31
WuXi Biologics Congratulates BioAtla on FDA Clearance of IND Application for CAB-AXL-ADC
Connecting Pharmaceutical Knowledge ispe.org 23
More Anchor and Exclusive Customers

Anchor Clients Exclusive Clients

Exclusive for Projects in Chinese Market

WuXiBodyTM Projects

Undisclosed Swiss Customer

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The WuXi Biologics Value Chain

Monoclonal Antibody Bi-Specific Antibody Fc-fusion Protein Antibody Drug Conjugate Recombinant Protein

Product Types

Discovery Assay/For- Cell Bank- Clinical & Lot

Novel Lead Research Cell Line Bio- Research Viral cGMP DS cGMP DP
Biology/ mulation/ ing/Cell Bio- Release/
mAb Drug Candidate Material Engineering/ Toxicology DMPK analytical Manufac- Process Line Char- Clearance Manufac- Manufac-
analytical Stability
Discovery Screening Selection Generation Construction Services turing Dev. acterization Validation turing turing
Testing Testing

Value Chain
Discovery Developability Assessment Preclinical/Development Clinical/Commercial

Global Supply Chain Network

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Rich Pipeline Across all Biologic Formats

205

• 51 First-in-class programs
131
• One of the largest portfolios
of complex proteins such as
Bispecifics, Antibody Drug
31 Conjugates (ADCs), and
19 14
10 fusion proteins
Total mAb Fusion ADC bsAb* Others
protein • All demonstrating globally
leading technical capabilities

mAb Fusion Protein ADC BsAb

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State-of-the-Art Technology Platforms
WuXiBodyTM Bispecific
1 Platform
• Combine any two antibodies and
assemble into bispecifics
• Easy to express, no aggregation or
mispairing, can be developed 6-18
months faster and much lower COGS
than competitor platforms
• Support 50+ projects per year which
attracts downstream services
WuXia Cell Line Platform
4 5 Technology
• Our own proprietary cell line paired
with our own proprietary algorithm
is more cost-effective, more efficient
and yields better results
• Capacity to develop 60+ cell lines
per year and includes in-house GMP
cell bank manufacture and
characterization
• Developed 290+ cell lines for
therapeutic protein purpose
Connecting
2 Transgenic Animal For
mAbs Discovery
• Access to OMT’s state-of-the-art
transgenic animal technology to
develop fully human antibodies with
high quality, specificity, expression,
solubility and stability
• Proven technology platform used by
20+ other global companies
• Support 50+ projects per year with
potential downstream services
Disposable Manufacturing
• No cleaning and sterilization required
for disposable bioreactors that use pre-
radiated plastic bags as the production
vessel in a stainless holder
• A facility using disposable bioreactors
can be built 12 to 18 months faster
with 30% to 50% less investment, and
can produce 5% to 15% more batches
of products with a higher success rate
Pharmaceutical Knowledge
Antibody Drug Conjugate
3
Discovery
• Integrate our in-house antibody
discovery, toxin and linker to deliver the
ideal lead ADC molecules
• Greatly simplify ADC drug development
by providing a one-stop shop
• 30 ongoing projects with ADC discovery
services with potential downstream
service
WuXiUP continuous
6 manufacturing platform
• The next generation biologic
manufacturing solution to accelerate
biologics development and
manufacturing as well as to improve the
affordability of biologics
• 30-50g/L titer (10-25X greater than Fed-
batch)
• Enabling 1,000L disposable bioreactors
to comparable productivity as traditional
SS tank through WuXiUP
ispe.org 27
Our Capabilities

Discovery and Material Generation

CMC Development

Clinical and Commercial Manufacturing

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Multiple Discovery Platforms

Comprehensive Capabilities
Phage Display
 WuXiBody Bispecific Engineering
TM

 WuXiLiAb® Phage Library Construction

 Traditional and Transgenic Rodent
Hybridoma Generation
 Humanization
Transgenic Rat /  Affinity Maturation
Rat/Mouse Mouse  HTS & Protein Analytics
Hybridoma Hybridoma  Functional Characterization

Connecting Pharmaceutical Knowledge ispe.org 29

Human Naïve Phage Library Screening

Panning/screening assay setup

1-4
weeks

3-4 rounds of panning with monitoring

enrichment by polyclonal phage ELISA
2-3
Features weeks

• Constructed in-house from 29 donors, 58 high

Selection output screening (phage
quality κ and λ sub-libraries
ELISA) 1-2
weeks
• Library total size 1.7x1011 containing more than
90% of error-free scFv transcripts
Hit confirmation/cross-reactivity
testing (phage ELISA and/or FACS) 1-2
• Systematically QC’d and verified library quality weeks

• Evaluated with 16 targets, delivered promising lead IgG conversion, scFv and IgG
for 12 projects expression, and functional testing
• Liquid-phase, solid-phase and cell-based panning
• 2-3 months turnover time for naive library Deliverables: 1-10 leads with varying
• 3-4 months turnover time for immune library binding/cross-reactivity profiles for
functional characterization

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 TM
- Bispecific Ab Platform

DIFFERENTIATION
• Universal: almost any mAb SPEED
sequence can be used to
build bispecifics No CMC challenges: no
• Flexibility: bi/tri/tetra expression, aggregation or
valency based on biology purification challenges –
Save 6-18 months of
development time

QUALITY
• Expected low
immunogenicity: natural
sequence without
complicated engineering
• Typical in vivo half-life to
mAb, longer than typical
bispecifics
More…

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Hybridoma Platform
Ligand’s OmniAb® Platform
Immunization and fusion Features

• AAALAC accredited and licensed animal facility

• Transgenic mice/rat for fully human antibody generation available Traditional
• Multiple immunogen choices (DNA, Peptide, Protein, Cell or combination) and WuXi
Biologics’ proprietary immunization protocol to increase chances of immune responses and Hybridoma OR
cross-reactivity.
• High fusion efficiency through electrofusion Approach
• Semi-solid method for subcloning

Screening Features

• High throughput protein-based and cell-based screening platforms.

• Binding screen by ELISA (protein-based), up to 200 plates/fusion
• Binding screen by Mirrorball (cell-based), up to 100 plates/fusion Immunization
• Binding screen by FACS (cell-based), up to 20 plates/fusion 6-8
weeks
• Well established reporter gene assay for functional screening
• 4 high-throughput flow cytometry and 5 Biacore to support screen Fusion and screening
• Abundant well established functional assays 3-4
weeks
Experience Subcloning & confirmation
3-4
• ~150 successful therapeutic antibody discovery projects via hybridoma platform weeks
• More than 20 successful hybridoma projects through OMT transgenic animal platform Antibody production and
• Extensive & successful experience in Ab discovery targeting GPCR & other difficult targets
hybridoma sequencing
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Largest Biologics Development Organization Among CDMOs
Total of ~1975 people as of Q2, 2019

122 154 241 224 85 418 102 102 151 375

Cell line development (CHO K1/CHO DG44) Protein Reagent Production

Cell Culture Process Development Purification Development

Drug Production Development Analytical Development

CMC Project Management Biologics Conjugation Development

Connecting Pharmaceutical Knowledge ispe.org 33

Integrated CMC Development (1)

CHO K1 CLD Platform

 Cell Line Development (CLD)
 = “Perfect/Ideal”
 FDA/EMA-compliant proprietary system
 290+ Cell lines developed for CMC/MFG
 High titer, stable platform (average 3.6 g/L)
 Competitive timeline (12 weeks to PCB)
 EMA-Certified GMP Cell Banking (10 suites
available)
 Cell Line Characterization (in-house)

Connecting Pharmaceutical Knowledge ispe.org 34

 Cell Culture Titers Profile

Clone Titer Distribution

30.3%
28.1%

19.1% Average Titer: 3.6 g/L

15.7%
Highest Titer: 9.2 g/L
5.6%

1.1%
Titer
(g/L)
<1 1-2 2-3 3-4 4-5 >5

Titer obtained using commercial media with limited development to

expedite IND filing and could be improved further
Data includes: mAbs, bispecific antibodies, fusion and recombinant proteins

Connecting Pharmaceutical Knowledge ispe.org 35

Integrated CMC Development (2)

Extensive PD Capacity Available

 Cell Culture Process
Development
 Advanced fed-batch processes
 High-density concentrated fed-
batch
 Perfusion process via ATF

Connecting Pharmaceutical Knowledge ispe.org 36

Integrated CMC Development (3)

Advanced Purification Process Development

 Standard 3 column purification process
 Customized purifications for fusion and recombinant
proteins
 Early Stage (1 – 20 mg scale)
 Small Scale (20 – 1,000 mg scale)
 Process Integration (500 mg – 5 g scale)
 Scale-up and Pilot Production (20 – 500 g Scale)
Ability to develop continuous downstream technologies also available

Connecting Pharmaceutical Knowledge ispe.org 37

Integrated CMC Development (4)

Formulation, Fill & Finish

 Provide end-to-end formulation development and fill/finish
services
 Three GMP filling lines:
 Bosch filling linefully automated for 2, 6, 8, 10, 14, 20 and 50 mL vials
 Flexicon filling line: non-standard vial sizes
 ADC liquid filling line

Connecting Pharmaceutical Knowledge ispe.org 38

Integrated CMC Development (5)

 Analytical  Mass Spec  Functional

 Quantitation  Intact Mass  ELISA/SPR antigen binding assay
 Physiochemical  Reduced Mass  FACS/ECL cell binding assay
 Glyco-profiling HPLC/UPLC  Deglycosylated Mass  Anti-proliferation, Apoptosis
 Higher order structure  Peptide mapping  Cytokine release, Neutralization
 Aggregate/product  Post-translational  ADCC, CDC, Adhesion
variants modification  Antigen specific immune response
 Impurities/contaminants

Connecting Pharmaceutical Knowledge ispe.org 39

State-of-the-art Forensic Analysis

 Identify unknown visible particles in lot release & stability samples;

 Identify unknown contaminants (such as color particles) in raw materials;
 Identify unknown particles and residues on manufacturing equipment and facilities;
 Examine and evaluate defects, malfunctions or failures of drug devices and containers;
 Trouble-shoot process-related abnormal events such as precipitation, filter clogging,
and unexpected deposition and residues

Key Equipment/Tools
• Stereo Optical Microscope • Fine Particle Manipulation Micro-tools
• Infrared Microscope • Raman Microscope
•Extensive Infrared and Raman Spectral Databases & Powerful Search Software
• Scanning Electron Microscopy (SEM) / Energy-dispersive X-ray Spectroscopy (EDS)

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Pilot Plant
 Material generation, process scalability and robustness evaluation
 Over 370+ batches executed since 2012 (＞98% success rate)
 15,000 sq. ft. Non-GMP clean room suites
 5 x 50 L + 7 x 200 L + 1 x 500 L disposable bioreactors
 3 x AKTA Process + 1 x AKTA Ready + 3 x AKTA Pilot + 2x Millipore Smart
 50 L + 200 L perfusion production

Connecting Pharmaceutical Knowledge ispe.org 41

 Ultra-high Productivity
Continuous Processing
 Process technology platform using
continuous cell culture and
continuous direct product capture

 Ideal not only for labile or difficult to

express proteins – but also mAbs, Fc-
fusion proteins etc.

 Enabling higher productivity with
rapid development, scale-up and
implementation at large scales
 Continuous approach effectively
reduces manufacturing cost of goods
Connecting
Case Study: Achieved cell culture productivity of an
Fc-fusion protein @ 2.5g/L/day and 51g/L bioreactor
volume after proprietary 20-day continuous cell
culture process.
More than 10 times productivity of 3-5g/L
traditional fed-batch process!
Pharmaceutical Knowledge ispe.org 42
Expedites Product Launch & Reduces Mfg. Cost

Comparable to
Traditional bioreactors
Enable 2,000L disposable bioreactors to
achieve comparable productivity as
traditional 20,000L stainless
bioreactors, significantly reduce the
manufacturing cost

High Purification Yield

Achieve ultra-high productivity while
enabling similar purification yield of the
traditional purification process

Scale-up to GMP
The technology is being scaled up to
GMP production and will be deployed
throughout our global manufacturing
network

Connecting Pharmaceutical Knowledge ispe.org 43

Capacities & Benefits of
 Lab scale
 48 x ATF2, w/ 1-15L bioreactor
 Dedicated DeltaV control system (Finesse)
 Pilot (non-GMP) scale
 2 x ATF4, w/15L and 50L bioreactors
 3 x ATF6 w/ 50-250L bioreactors
 Clinical GMP Production
 2 x 250L w/ ATF6 (@Wuxi MFG1)
 1 x 250L w/ ATF6 & 1 x 500L/1000L w/ ATF10
(@Shanghai MFG3)
 Commercial GMP Production
 2x 1000L w/ ATF10 (Wuxi MFG2)
 3x 2000L w/ ATF10 (Wuxi MFG4)
Connecting Pharmaceutical
Comparison with traditional fed-batch
• Achieving roughly same production cell culture
timelines with 5-10X yield with high cell
concentrations, high cell viability and better or
comparable product quality profiles
• Tunable glycan and charge variance profiles,
usually with reduced HMW and LMW
• Higher viable cell concentration and lower cell
specific perfusion rate able to reduce media
consumption & harvest volume
• Higher production facility efficiencies leading
to lower COGs
Knowledge ispe.org 44
World-Class Facility in Wuxi City (MFG 1)
cGMP Biologics Manufacturing

GMP plant in full operation since Q4 2012

Biologics DS/DP clinical manufacturing
ISPE 2014 “Facility of the Year” Special Award (1 x 500/1,000 L, 2 x 2,000 L)
Biologics/ADC DS/DP release testing and stability
Approved for Commercial Production
Connecting Pharmaceutical Knowledge ispe.org 45
World-Class Facility in Wuxi City (MFG 2)
World’s largest mammalian cell culture mfg. facility using disposable bioreactors
7 x 2,000 L
Fed-batch/Concentrated
Fed-batch Cell Culture

Facility A
Polishing
Capture
7 x 2,000 L Purification
Fed-batch/Concentrated
Fed-batch Cell Culture

Facility B
2 x 1,000 L (200-1,000 L wv)
Perfusion Polishing
Cell Culture and Capture Purification

Finished PPQ at 6000L scale and run multiple batches at 12000L scale
Connecting Pharmaceutical Knowledge ispe.org 46
New GMP Facility in Shanghai (MFG 3)

200,000 sq. ft. new

state-of-the-art center:
30,000 sq. ft. PD lab

GMP clinical DS facility

 4 fed-batch lines (2 x 2,000 L;
1 x 1,000 L; 1 x 200 L)
 2 perfusion lines (1 x 200/500 L;
1 x 1,000 L)
 Site increases 2X our clinical mfg.
capacity
 Enable 10 concurrent GMP
campaigns at WuXi Biologics
Connecting Pharmaceutical Knowledge ispe.org 47
Expansion in Wuxi City (MFG 4/5/9)

 Goal: To build one of the largest

biotech hubs globally
 4MM sq. ft. for Discovery,
 Development and Manufacturing
 Clinical and Commercial
Manufacturing
 Up to 200,000 L DS capacity
 PFS and vial DP

New GMP Facility Expansion

WuXi Biologics to Install Industry’s Largest Single-
Use Bioreactor from ABEC at its New Commercial
Manufacturing Facility (MFG 4)
Connecting Pharmaceutical Knowledge ispe.org 48
Robust Global DS (280,000 L) Supply Chain
Site # DS Capacity GMP Ready Location Comments
MFG1 5,000L fed-batch/perfusion 2012 Wuxi Commercial
MFG2 28,000 L fed-batch / 2,000 L perfusion 2017 Wuxi Commercial

MFG3 5,200 L fed-batch / 1,500 L perfusion 2018 Shanghai Clinical/Comm

MFG4 10,000 L fed-batch/CFB 2019 Wuxi Clinical/Comm
MFG5 60,000 L fed-batch 2020 Wuxi Commercial
MFG6 6,000 L (6 x 1,000 L) perfusion 2021 Ireland Commercial
MFG7 48,000 L fed-batch 2021 Ireland Commercial
MFG8 48,000 L fed-batch 2021 Shijiazhuang Commercial
MFG9 10,000 L fed-batch/CFB 2021 Wuxi Clinical/Comm
MFG10 4,000 L fed-batch / 500 L Perfusion 2021 Singapore Clinical/Comm
MFG11 4,000 L fed-batch / 500 L Perfusion 2022 Worcester, MA Clinical/Comm
MFG12 48,000 L (12 x 4,000 L) fed-batch 2022 Chengdu Clinical/Comm

Connecting Pharmaceutical Knowledge ispe.org 49

Rapid Expansion of DP Capacity

DP Capacity GMP Ready Location Comments

Liquid vial with
DP1 2013 Wuxi Commercial
lyophilization
Liquid vial with
DP2 2020 Wuxi Commercial
lyophilization
DP3 ADC conjugation and DP Q3 2019 Wuxi Clinical
DP4 Vial/PFS Q3 2019 Wuxi Clinical
DP5 Commercial PFS 2021 Wuxi Commercial

Connecting Pharmaceutical Knowledge ispe.org 50

DP1: Drug Product Manufacturing Facility

• Operational since 2013, 300+ batches completed to support global trials

• State-of-the-art facility based on US/EU/Chinese cGMP requirements
• Both liquid and lyophilization vials (2/6/8/10/14/20/50mL)
• Fully automated vial wash, depyrogenation, filling and capping line from
Bosch in oRABS
• Capacity at 12,000 2-mL vials per hour, or 100,000 per batch
• Piston pump and peristaltic pump filling system for choice
• 5m2 lyophilizer with fully automated loading and unloading

Connecting Pharmaceutical Knowledge ispe.org 51

DP1: Vial Size & Capacity

Vial Size, mL Liquid fill rate, vials/hr Liquid fill capacity, vials/batch Lyo capacity, vials/batch
2 12,000 84,000 22,400
6 8,500 59,500 11,000
8 8,500 59,500 11,000
10 8,500 59,500 11,000
14 7,800 54,600 10,070
20 5,300 37,100 6,195
50 1,300 9,100 3,300

Connecting Pharmaceutical Knowledge ispe.org 52

DP4: Facility for Vials and PFS Ready Q2 2019

Prep.

Vanrx SA25

Formulation
C Corridor

Connecting Pharmaceutical Knowledge ispe.org 53

DP4: Vanrx SA25 Aseptic Filling Workcell

Large pharma/biopharma also adopted

the Vanrx technology

• Vanrx SA25, isolator in Grade C, no glove needed

• Filling type: peristatic pump, single head (1 filling
needle)
• Filling volume range: 1 – 100 mL
• Container type: Vial and PFS
• Weight check: 100%
• Max speed: 25 units/min

Connecting Pharmaceutical Knowledge ispe.org 54

ADC and Bio-conjugates

mAb Linker Payload ADC

Lab-scale     TDC NNAA Bispecific-ADC
Non-GMP pilot scale    
cGMP manufacturing
> 2kg > 5kg > 5kg Up to 1kg*
scale per batch
Enzyme-
Lys based Cys based
 Multiple conjugation strategy assisted
 Diversified protein/antibody/polymer conjugation
Micelle
 Library of drugs and linkers
 Analytical capabilities KIH
 Formulation development / stability studies
 Bioactivity and DMPK analysis
PEGylation
New DP3 GMP facility ready and expanding to O
O
O
commercial GMP of bioconjugate DS and DP by 2022 n

Connecting Pharmaceutical Knowledge ispe.org 55

DP3: GMP ADC Manufacturing Facility

 Dedicated and segregated area (66,000 sq ft) for high

potency conjugation, formulation and fill/finish including
lyophilized ADC, cytotoxin and small molecule Injectables
 OEB5 Isolator for payload-linker dispensing and
dissolution preparation
 Single-used bioreactor and filling line to avoid cross-
contamination
 ADC conjugation batch scale up to 2 kgs
 Fully automated vial washing, depyrogenation, filling, and
vial loading-unloading
 Nitrogen blanketed filling and light protected production

Connecting Pharmaceutical Knowledge ispe.org 56

DP3: Dedicated GMP Filling (Liquid & Lyo) for ADCs

• High-potent DP filling and lyophilization in isolator-based system

• Up to 100,000 2-mL vials/batch (liquid) and 6,000 20-mL vials/batch (lyo)
• 50 batches/year – 300 K vials/year

Connecting Pharmaceutical Knowledge ispe.org 57

57
U.S. FDA & EMA -Approved Quality System

 Strong quality leadership team:

 CQO + 2 VP + 9 Sr. directors + 3 Former FDA consultants
 Recent FDA PLI: one of the most extensive PLIs
 5 FDA Investigators for 13 days
 1463 documents reviewed
 1028 questions answered
 133 SMEs interviewed
 481 data integrity-checks
 39 site tours

Connecting Pharmaceutical Knowledge ispe.org 58

Our Capabilities Summary

The world’s ONLY single-source platform from concept to commercialization

Integrated discovery services utilizing hybridoma, phage

display and transgenic mice.

Pre-clinical assessment of lead mAb candidate and

developability study for early stage de-risking.

Integrated cell line and process development supported

by state-of-the-art analytical and bio-assay services.

World’s largest mammalian cell culture manufacturing The World’s ONLY single source
facility using disposable bioreactors, reflects WuXi’s
platform from concept to
vision of market trend.
commercialization and expanding
global supply chain (4 countries)

Connecting Pharmaceutical Knowledge ispe.org 59

Why WuXi Biologics?
U.S. FDA & EMA Approved Quality System for Commercial Manufacturing
Cutting • WuXiBodyTM bispecific (universal, 6-18 months of time-saving, no CMC issue)
Edge • WuXia cell line (robust cell line with proven track record)
• WuXiUP continuous manufacturing platform (30-50g/L titer, 10+x)
Technology
IND Filing Timeline
Best • Industry average: 18-24 months
Timeline • WuXi average: 15 months
• WuXi record: From 9 months to 7 months

Excellent • 100% projects delivered

Track • No customer transfer out
• Excellent customer satisfaction and high recognition
Record

• 60 INDs and 5 BLAs per year

Unparalleled • Largest scientist team in the world: 1,975
Capacity • Largest capacity using single-use bioreactor: 280,000 L by 2022

Connecting Pharmaceutical Knowledge ispe.org 60