To support our clients and to overcome the challenges associated with complex modalities such as bispecific antibodies (bsAb) and multispecific antibodies (msAb), WuXi Biologics has established the WuXiBody and SDArBody bsAb and msAb engineering and development platforms.
Bispecific/Multispecific Antibody Platforms
Novel Technologies Providing Flexible Valency and Outstanding Developability
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Bispecific antibodies (bsAbs) and multispecific antibodies (msAbs) are a growing class of biotherapeutics that come with many engineering and development challenges. WuXi Biologics established the WuXiBody and SDArBody technology platforms to overcome these challenges and meet the needs of biologics developers pursuing different biology and therapeutic approaches via these novel modalities. WuXiBody TM A proprietary, highly flexible engineering platform that greatly enhances the developability characteristics of bsAbs. SDArBody TM A unique platform utilizing single domain antibodies (VHH) as building blocks to further facilitate the exploration of more complex biologics such as msAbs.
Overcoming Technical Challenges of BsAbs and MsAbs Platforms
WuXiBody TM BsAb Technology Platform
The technical challenges of developing bsAb and msAb include: (A) the engineering challenges to solve chain mispairing issues; (B) Developability issues that impact manufacturing efficiencies and costs or clinical efficacy and safety Primary Technical Challenges
The WuXiBody platform is an innovative, proprietary technology platform developed for the expanding use of bispecific antibodies as therapeutics. Based on novel engineering, the platform expedites the drug development process by 6-18 months and significantly reduces production costs. This platform takes almost any monoclonal antibody (mAb) sequence pair and assembles it into a bispecific construct. The platforms unique structural flexibility allows for efficient construction of various formats with different valency (e.g., 2, 3 or 4 binding sites).
(A)
(B)
E icacy
Safety
Examples of formats enabled by WuXiBody
Side Products (chain mispairing)
VH
VH
VL
VL
Clinical Candidate
Immunogenicity
PK/PD
CH1
CL
TCR Cꞵ
TCR Cɑ
Physio Chemical Properties
A
A
A
A
A
A
B
B
B
Manufacturability
B
B
A
A
B
B
B
A
B
B
B
A
B
B
B
1+2
2+2
1+1
1+2
2+2
1+1
1+2
2+2
WuXiBody and SDArBody platforms were developed to overcome these challenges.
The WuXiBody platform enables our partners to take any two monoclonal antibodies (mAbs) and engineers these into a highly-functional bsAb and to bring those novel bsAbs into the clinic significantly faster and with titers and yields rivaling regular mAbs.
Target Biology
Ab Engineering
Development
Flexibility: 1+1, 1+2 or 2+2 binding sites Pharmacokinetics: long in vivo half-life
Universality: Compatible with most mAb pairs
Strong Developability: High titer, yield, solubility and serum stability
X months
2-4 months
16-18 months
WuXiBody TM
Targets
mAbs
IND-ready
WuXiBody TM Advantages
Fast development and no CMC challenges
Development/CMC Advantages
Engineering Advantages
• Saves 6-18 months of development time • Reduces manufacturing costs by as much as 90% • Can be used in both fed-batch and concentrated fed-batch production • Provides high protein expression in CHO cells (2-5 g/L, >30 g/L intensified perfusion culture (IPC)) • No aggregation issues • Very stable: >2 weeks in serum at 37 °C • High solubility: 30-100 mg/ml • Similar yield to mAbs
• Compatible with almost any mAb sequence • Available in both symmetric and asymmetrical formats
• Accommodates different valency formats (bi, tri and tetra) based on project needs and biology • Provides similar purification schemes as for mAbs • Ensures long In vivo half-life • Utilizes natural human sequence without complicated engineering resulting in low immunogenicity
SDArBody TM MsAb Technology Platform
SDArBody is a novel technology platform to enable the generation of multispecific proteins utilizing WuXi Biologics’ unique VHH libraries and discovery capabilities. This highly flexible platform offers our clients the ability to generate multispecific antibodies with high affinity, low immunogenicity risk and excellent developability characteristics.
Multiple Approaches to Discover VHH Leads
VHH Optimization
SDArBody Engineering
• >10 11 size naïve library from 100+ alpaca donors • >10 11 size humanized synthetic VHH library • Immune library based on proprietary immunization protocol to achieve desired immune responses Phage display • Cutting edge Berkeley Lights Beacon system • Proprietary antibody to isolate alpaca plasma cells Single B cell selection
Humanization
VHH Advantages: • High Affinities • Smaller molecular size • Ideal for binding to difficult targets and epitopes • Excellent developability • Low immunogenicity risk • Great flexibility in building multispecific biologic
A inity Maturation
1-4 months
2-3 months
1-2 months
Multiple VHH lead generation and screening approaches have been developed for the SDArBody platform, including traditional phage display, and single B cell selection. After humanization (and optional affinity maturation), the VHH leads can be freely assembled into SDArBody msAb.
Other BsAb and MsAb platforms from WuXi Biologics
WuXi Biologics offers expertise and additional technology platforms beyond WuXiBody and SDArBody for the development of bispecific antibodies (bsAbs) and multispecific antibodies(msAbs). Our other platforms includes scFv and transgenic hybridoma approaches as well as experience with many technologies readily available in the public domain. To learn more, please visit: wuxibiologics.com/discovery/bispecific-antibody
WuXi Biologics General Platform
Transgenic Rats with Common Light Chain
• Extensive engineering provides more stable scFv • SKYBody bsAbs and msAbs demonstrate good developability characteristics Proprietary platform for bsAbs generated using scFv
• Experience with 100+ formats available in the public domain • Engineering of bsAbs and msAbs using scFab and scFv • Optimize molecules to improve developability while maintaining antigen-binding
• Fully human antibody repertoire using transgenic rodents • Generates antibodies with common light chain –ideal for bsAb development
Integrated End-To-End Discovery Services
What makes WuXi Biologics unique is our integrated, one-stop biologics discovery and development service platform from target to IND. Our comprehensive single-source services reduce risk and save significant time by incorporating developability assessment into the discovery activities. To learn more about our integrated discovery services, please visit: wuxibiologics.com/discovery
DISCOVERY
CMC DEVELOPMENT
Target (Concept) Target Evaluation Reagent Material Generation
Lead Optimization & Characterization Optimization (e.g., humanization, affinity maturation, Fc engineering) In vitro characterization (e.g., binding, epitope binning & mapping, functional assays) In vivo characterization (e.g., PK/PD, tox, efficacy, tumor models, ex vivo studies)
Antibody Discovery Monoclonal, bispecific & multispecific antibody engineering, generation and screening Hybridoma (including transgenic), phage display, VHH immune libraries and single cell B cloning platforms Other molecule modalities (antibody fragments, fusion proteins, ADCs etc.)
IND Filing Support Clinical development plan/ protocols & registration support Pre-IND meeting, CMC Dossier preparation, & regulatory affairs consultation
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.
11-21-2023
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