adc - chempartnerantibody-drug conjugation with different chemistries. validated adc production and...
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ADCDiscoveryADCDiscovery
Biologics
Well Established ADC Preparation andCharacterizationProceduresAntibody-drug conjugation with different chemistries.Validated ADC production and purification process.
PKMouse, rat, monkey Bioanalytical development PK/PD modeling &simulationIn vitro stability in biological matrices
Pharmacology, PKPD & Exploratory Toxicity
High potency lab facility to limit toxin exposure (OEL < 1ug/m3)35 chemists with experience in payloads and linkers Resynthesis of Kadcyla and Adcetris from Mertansine and AuristatinIdentification, synthesis and modification of toxinsLinker design, synthesis and evaluationOptimize payload-linker for overall profile
Chemistry
EstablishedChemistry Capacity
998 Halei Road #5 Zhangjiang Hi-Tech Park PudongShanghai, China 201203China: +86 21 5132 0000 USA: +1 781 996 5291Europe: +45 4586 9000 Japan: +81 3 [email protected]
Jason Xiang, Ph.DExecutive DirectorTel: +86 21 5137 [email protected]
Louis LiuExecutive DirectorTel: +86 21 [email protected]
Contacts
Complete ADC quality control and characterization methods.
ELISA, FACS and Biacore for antigen binding activity.Cell based assays for in vitro efficacy and bioactivity of antibody and ADC.Quality control in each production step for drug to antibody ratio (DAR), purity, aggregation, endotoxin, residues of free drug and solvent, etc.Advanced analytical tools and technologies, LC-MS, HPLC-HIC SEC, iCIEF, peptide mapping, conjugation site mapping, etc.
Dedicated ADC conjugation labs and In-Process QC equipments.
Exploratory Toxicity Single dose, repeated dose, dose range finding.
PharmacologyEfficacy Studies 124 cell line xenografts and 162 PDXs (patient derivedxenograft)Positive and negative controls
BiodistributionImaging with labeled mAb Ex vivo tissue concentration analysis
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Extensive characterization methods are availablefor ADC product analysis
As a case study, Herceptin-DM1 (T-DM1) was prepared and its PK profile is similar to the published data
No internalization Internalized
AntibodyInternalization
Assay
PK parameters Unit Total Ab
CL mL/day/kg 7.44Vss mL/kg 84.8V1 mL/kg 37.2
Alpha t1/2 day 0.0248Beta t1/2 day 7.94
PK parameters Unit T-DM1CL mL/day/kg 13.3Vss mL/kg 113V1 mL/kg 52.3
Alpha t1/2 day 0.0622Beta t1/2 day 5.93
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Acute toxicity of T-DM1 from a case study was assessed. Results showed tested ADC products are well-tolerated at the tested dosages.
In vivo efficacy results from T-DM1 case study using NCI-N87 gastric cancer xenograft model. Data showed full regression of tumor after treatment with 15mg/kg of ADC.
Antibody Internalization Assay LC-MS analysis of ADC
Tumor volume changes of SCID mice intreatment of NCI-N87 xenografts
0 7 14 21 28 35 42 490
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3000Vehicle, ivHerceptin, 3mg/kg, ivHerceptin, 15mg/kg, iv
T-DM1, 3mg/kg, ivT-DM1, 15mg/kg, iv
Days post grouping (day)
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