Integrated in vivo pharmacology services (PK/PD/Tox, efficacy and immunohistology) to evaluate diverse therapeutic modalities, supporting preclinical studies, IND filing and beyond
In Vivo Pharmacology Services
Integrated In Vivo Pharmacology Services • Pharmacokinetics (PK) and pharmacodynamics (PD) • Efficacy • Toxicology • Immunohistology
With experience spanning over 800 projects, WuXi Biologics offers integrated, end-to-end in vivo pharmacology services across diverse therapeutic modalities, including monoclonal and bispecific antibodies, ADCs, fusion proteins, and CAR-T therapies. Our deep expertise in key therapeutic areas such as oncology, autoimmune diseases, inflammatory disorders, and diabetes ensures streamlined support from preclinical studies through IND filing and beyond.
In Vivo and Ex Vivo Capabilities
Efficacy Study
Our in vivo and ex vivo capabilities encompass multiple species, extensive PK/PD/Tox studies, and a broad array of efficacy models, delivering actionable insights into mechanism of action (MOA), distribution, and drug candidate efficacy to accelerate your biologic drug projects.
G4 Ab2 3mg/kg G5 Ab2 0.5mg/kg
G1 Control 3mg/kg G2 Ab1 3mg/kg G3 Ab1 0.5mg/kg
10e+06 10e+05 10e+07 10e+08 10e+09 10e+10 10e+11 10e+12 0.1 1 10 100 1000 10000 100000
Tumor-Luciferase Reporter
In Vivo Efficacy Study Models
PK, PD, and Exploratory Toxicity
Multiple Species
Days Post Grouping 0 3 6 9 121518212427
• Mouse, rat and monkey • PK, PD, IHC
• Syngeneic
Rodent PK Study
Humanized/WT • CDX; CDX/PBMC • GVHD • Autoimmunity • Rare disease • Metabolic disease
• In vivo imaging and bio-distribution • In vitro , ex vivo biomarker and MOA studies
Ab1 10 mg/kg Ab3 10 mg/kg Ab2 10 mg/kg
Organ Distribution Analysis
0
3
6
9
12
15
IHC Staining
Time (day)
Holistic PK, PD, and Toxicity Studies
• Rapid response: Monkeys scheduled within 7 days • Highly customized assay development • Flexibility: Adaptable to specific client requirements • Data interpretation: Insightful analysis for integrated projects • Total timeline: 6–11 weeks PK, PD, and Toxicity Service Features
Our comprehensive PK, PD, and toxicity studies include multi-species screening, a dose-concentration-response evaluation, and a determination of safe dosage levels, facilitating leads optimization and supporting every stage of drug development, from early discovery to IND filing.
PK
PD
Tox
Immunophenotyping
Cytokine Analysis
Hematology
TCE-2_(1) TCE-2_(10)
0.1 1 10 100 1000
30 40
150
1000 2000 3000 4000
WBC#
TCE-2 1 mg/kg TCE-2 10 mg/kg
TNF
0 5.58 10 20 26.6
100
p
50
Day-3 0
-72h 1h 2h 4h 8h 24h 144h 0
Time (Day) 0 1 2 3 4 5 6 7
Bio-distribution
TA-12, 15 mg/kg, Male TA-12, 15 mg/kg, Female Receptor Occupancy
Histology
0 20 40 60 80 100
Stained inflammatory cells
0 7 1421 283542 Days a er the treatment
-1
Extensive Efficacy Model Collections
29 Autoimmune Disease Modes
15 Syngeneic Models
87 CDX (PBMC) Models
27 IVIS Imaging Models
7 Metabolism Models
Immunology & Metabolism
Oncology
*Build engineered cell-lines and establish new models on demand
Comprehensive Immunohistology Capabilities
• Comprehensive panel of staining methods: Includes HE, IHC, IF, EHC, and TCR • In-depth tissue analysis: Target evaluation, antibody distribution, immune cells infiltration, and more • Qualified pathology analysis
T Cell Infiltration
Tumor Antigen IHC for Model Characterization & Selection
HE Staining
PBS
mAb1
mAb2
Relative Quantification
***
***
50
Lung Lung
40
High expression High expression
Medium expression Medium expression
Low expression Low Expression
Kidney
30
Multiplex IF for Immuno-Profiling
20
10
0
PBS
mAb1
mAb2
DAPI
hCD4
hCD8
Merged
Case Study 1: Single-Source Solution for In Vivo Characterization of TCE
In this case study, the PK of TCEs was evaluated in vivo . The dose-concentration-response relationship for efficacy was also determined using a cell-derived xenograft (CDX) and peripheral blood mononuclear cells (PBMC) model designed based on tumor target validation through immunohistochemistry (IHC).
Customized PK Platform for TCE
CDX/PBMC Efficacy Model for TCE NCI-H524 in NDG-hPBMC
Biotin
TCE-1 Fc+Fc TCE-1 CD3+Fc
1000
PBS B (0.54 mg/kg) B (0.18 mg/kg) B (0.06 mg/kg) A (0.36 mg/kg) A (0.12 mg/kg) A (0.04 mg/kg) W (0.45 mg/kg) W (0.15 mg/kg) W (0.05 mg/kg)
1000 1500 2000 2500
100
Fc-Fc
Target validation
10
• Customized PK platform: Enables precise measurement of total IgG and TCE levels • Validated CD3 antigen: Ensures specificity and efficacy • Rationally designed CDX and PBMC efficacy model: Supported by target validation to enable potent PBMC donor screening Case Study 2: Established hFcRn Mouse Model for Early-Stage Fc Engineering Assessment 0 7 14 1 Time (Day) CD3-Fc 0 7 14 0 500 Days aer treatment
21
In this case study, we use a well-established hFcRn mouse model to assess Fc engineering at an early stage and simulate the in vivo PK profiles of both human mice and non-human primates (NHPs). • Enhanced PK profiles: An Fc-engineered antibody shows improved PK compared to its wild-type counterpart. • Strong linear correlation in t1/2: A consistent t1/2 correlation was observed between hFcRn and NHP models.
PK Curve of hFcRn Mice IV Infusion
Linear Simulation of t 1/2 Between hFcRn Mice and NHP
5 10 15 20 25
Pearson’s r = 0.91; P < 0.001
1000
G1_Wt t1/2=113 G2-Fc Engineered t1/2=260h
100
10
1
5
10
15
20
25
0.1
hFcRn mice half life (days)
0
7
14
21
Time (Day)
Valente et al; mAbs; 2020, VOL. 12, NO. 1, 13
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.
The world’s leading global single-source platform from concept to commercialization
wuxibiologics.com | PS_BD@wuxibiologics.com
12-3-2024
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