Antibody Drug Conjugates
Antibody Drug Conjugate (ADCs)
Syngene’s Antibody Drug Conjugate (ADC) unit brings together an array of multidisciplinary capabilities in antibody generation, linker and payload chemistry, conjugation chemistry, in vitro and in vivo oncology in an integrated platform.
Integrated ADC Discovery, Development and Manufacturing - Breadth of service under one roof: Syngene’s Antibody Drug Conjugate (ADC) unit brings together an array of multidisciplinary capabilities in Antibody Discovery and Engineering, Antibody Development and Manufacturing, Linker Optimization, Linker and Payload Development and Manufacturing, ADC Conjugation Development and Scale-up, In vitro and In vivo Oncology, Pharmacology and Toxicology on an integrated platform.
The services are offered in integrated, clustered and standalone as needed by our customers
- Antibody engineering for conjugation and other optimizations
- Linker chemistry: Optimization and evaluation, experience of cleavable, self-immolating and non-cleavable linker systems, click Chemistry based linkers, peptide based linkers, dendrimers, etc.
- Payload chemistry: Novel and standard payloads (Duocarmycin, Auristatin, Tubulysin, DM1, DM4, SN38, Etoposide, Bleomycin, Podophyllotoxin, etc), synthesis and derivatization of Toxins.
- Conjugation chemistry: Thiol based, using engineered and native Cys residues in antibodies; Lys based and others.
- Cytotoxic development and cGMP manufacturing
- Conjugation strategy and process development
- Conjugation scale up and cGMP manufacturing (Facility upcoming)
- Analytical method development
- In vitro evaluation (binding, internalization, potency etc.)
Generation and rapid evaluation of ADC panels
Selecting the best mAb and an appropriate linker-payload system for a particular cancer target can be a daunting task at an early discovery stage of ADCs. Syngene offers the capacity to generate a Panel of ADCs combining (Conjugation) a set of lead mAbs (Antibody Panel) and linker payload systems (non-proprietary and client licensed Linker technologies) at a small scale followed by their analytical (Aggregation, Affinity, Payload stability and cytotoxicity), Pharmacokinetics, and in vivo efficacy evaluation.
ADC evaluation and Analytical offerings includes the following:
- mAb: Target engagement, Species cross reactivity, Internalization, PK properties (half-life of naked mAb), Tumor targeting and off site accumulation (whole animal imaging), Stability and other physico-chemical properties
- ADC: LC ESI MS: DAR, HIC: DAR and homogeneity, SE HPLC: Agreegation, LC MS: Free drug, Antigen binding: SPR and Flow Cytometry, In vitro potency: Survival assays (MTT), spheroid, Plasma and pH stability: LC MS, Payload release: LC MS, In vivo pharmacology, Tumor growth inhibition (ATCC cell lines and PDX), PK (ADC, Free-drug, DAR), Tox (Rodent (both GLP, non-GLP)
- Linker-Payload: Potency, Solubility, Plasma and pH stability, Payload release kinetics, Payload cellular stability and other analytical properties.
ADC Generation - Scale:
ADC Manufacturing Scale
- Discovery: 20-500 mg (ADC)
- Process Development: Up to 3 g (ADC)
- Manufacturing: Up to 500 g (ADC).
- cGMP Conjugation Facility: Single use technlogy up to 200L conjugation scale followed by chormoatographic purification used in the facility under development.
- Dedicated high-potent compound handling labs (Link to CD)
- Dedicated isolators for conjugation (OEL band 5 or equivalent)
- Purification systems
- Mass spec
- HPLC etc
Key projects completed
- Discovery and proof-of-concept of a patentable novel linker system
- Discovery and development of an ADC (currently nearing IND submission) using client-licensed linker technology
- Rapid generation and evaluation of ADC panels (various technology platforms) conjugation through in vivo efficacy