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Bioconjugation Discovery
Extensive R&D capabilities and world-class expertise
Extensive R&D capabilities and world-class expertise is available at WuXi XDC to generate, engineer, evaluate and optimize antibody drug conjugate (ADC)/bioconjugate lead candidates including trouble-shooting and overcoming the challenges associated with complex bioconjugated moieties. Wide-ranging R&D of the bioconjugation key intermediates, including mAb/protein, payload and linkers, is also available and is a cornerstone of the WuXi XDC technology platform.
Comprehensive Capabilities and Vast Project Experiences from ADC to XDC
From ADC to XDC, the boundaries of bioconjugates are continually expanding. At WuXi XDC, we have conducted a vast array of projects across bioconjugation landscape. Our capability from ADCs to XDCs:
- ADC/BsADC/Dual Payload ADC
- Antibody-Oligonucleotide Conjugate
- Antibody-Chelator Conjugate
- Degrader Antibody Conjugate
- Immuno-Stimulant Antibody Conjugate
- Antibody-Peptide Conjugate
- Vaccine Conjugate
- PEGylation-Based Conjugate
- Protein-Protein Conjugate
- Antibody-Glycan Conjugate
- Antibody-Fluorophore Conjugate
- Peptide-Oligo Conjugate
- and more…
Bioconjugation Discovery Services & Capabilities Overview
High-throughput Conjugation
To maximize the efficiency of your drug discovery efforts, we use a state-of-the-art high-throughput ADC conjugation platform and a highly vetted project management system to facilitate ADC candidate selection. We utilize high-throughput (HTP) methodologies for the generation and evaluation of antibody intermediates at microgram scale. In the example to the right, IgGs from hybridoma crude culture media, regardless of their concentrations, can be made into ADCs of the same DAR (tunable from DAR2-DAR4 and with low residual free drug) for batch analyses and selections of antibody for further evaluation.
Conjugation Capabilities
The discovery services team at WuXi XDC applies multiple methods for the synthesis of bioconjugates between payloads that include protein degraders, peptides and oligonucleotides, etc. and macromolecules that include proteins (e.g., antibodies, fusion proteins), amongst others. We use many types of conjugation technologies including traditional cysteine- and lysine-conjugation, and many of the widely used site-directed conjugation methods such as THIOMAB™, non-natural amino acid incorporation, and glycol site- and enzyme-assisted conjugation. Our bioconjugation experience encompasses multiple carriers and an extensive linker and payload library is available for your R&D purposes as demonstrated in the table:
State-of-the-Art Conjugation Technology
The discovery team at WuXi XDC has extensive experience in various bioconjugation types. Over 10 conjugation technologies are applied to generate conjugates.
- Lysine (random)
- Interchain cysteine (random)
- Interchain cysteine (site-specific): WuXiDAR4
- Interchain cysteine (site-specific): ThioBridge
- Cysteine (site-specific): THIOMAB
- mTransglutaminase
- Sortase A
- Farnesyltransferase (ConjuAll)
- GlycoConnect (glycosyl transferase)
- Affinity peptide-mediated conjugation
- And more
Proprietary Drug-to-Antibody Ratio and Enrichment Technology
The most clinically validated conjugation sites, including those used by many blockbuster ADCs, are interchain cysteines. Using these sites as a foundation, WuXi XDC developed the novel WuXiDARx™ conjugation platform. WuXiDARx™ provides a highly flexible drug-to-antibody ratio (DAR), demonstrated homogeneity, compatibility with native IgG1 and many commonly used linker-payloads, and a simplified CMC process. This technology is valuable not only at the discovery stage to streamline ADC engineering and identify the optimal DAR when screening antibody and linker-payload combinations, but also at the CMC stage to accelerate CMC development and reduce development risks and eventual large-scale manufacturing costs.
WuXiDARx™ offers the following advantages:
- Flexible DAR approaches: DAR2, DAR4, and DAR6
- High homogeneity of a single conjugated species: ≥ 65% without column purification; ≥ 95% with column purification
- Compatibility with native IgG1: no protein engineering modifications required
- Compatibility with common linker-payloads: no connector modifications needed
- Cost-effective bioconjugation process
WuXiDAR4™ is our most advanced WuXiDARx™ platform. ADCs produced from WuXiDAR4™ demonstrated comparable cytotoxicity to ADCs produced by conventional stochastic conjugation methods, but demonstrate better PK profiles and tolerability. So far, seven ADC molecules, generated via the WuXiDAR4™ platform, have entered clinical trials.
Flexible Developability Study Packages for your Bioconjugates
Gram-scale conjugation identifies potential challenges and risks during development.
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