Early-stage biologics drug developability testing using <1 mg antibody completed within 2 weeks, from in silico analysis, PK prediction to biophysical analysis.
Early-Stage Developability Assessments for Lead Optimization · In Silico Analysis · Off-Target/PK-Assessment · Mass Spec · Biophysical · Forced Degradation Studies
Developability is a Key Criteria WuXi Biologics’ Micro Developability Platform is specially designed to support early- to mid-stages of drug discovery, offering a suite of high-throughput (HTP), low-sample-consumption assays that can evaluate biophysical properties, PK, and manufacturability. Early-stage screening for therapeutic antibodies often prioritizes binding affinity and function, while critical developability factors are frequently overlooked, leading to CMC and clinical challenges. WuXi Biologics has developed the Micro Developability platform, a HTP analytical suite that requires less than 1 mg of antibody. This platform utilizes HTP in silico screening and early-stage developability testing to assess biophysical properties, PK, and manufacturability. By analyzing critical developability aspects with expert interpretation, these early assessments help optimize leads, mitigate downstream risks, and facilitate a seamless transition to CMC development.
In Silico Analysis · Sequence liability · Immunogenicity · Aggregation
STAGE I
i l
STAGE II
Poly-Specificity /PK-Predicting · AC-SINS (self-interaction) · BVP/DNA/Insulin ELISA · Human FcRn affinity · Serum stability (cleavage)
STAGE III
Manufacturability · Biophysical: DSF · Stability: thermo, F/T, pH · Mass spectrometry: · Peptide mapping · CIEF-MS
· Sequence liability · Immunogenicity · Off-target binding/poly-specificity · Poor stability CMC
Total sample required: <1 mg for most assays
Features and Applications
Key Features of the Platform:
· Mass Spec analysis · <1 mg protein needed · HTP evaluation of many molecules at research stage
· Early stability assessments · In silico analysis (Figure 1) · Off-target/PK-assessment assays (Figure 2) · Biophysical characterization
Figure 1
Figure 2
Liability · Post-translational modification · CDR hotspots · Free cysteine · Fc mutation · Amino acid usage frequency
Aggregation · Structure prediction · Hydrophobicity based · Free cysteine based
Immunogenicity · Sequence similarity based · MHC based · Humanization
AC-SINS
Evaluation of self-association tendency
AC-SINS
BVP/DNA/Insulin ELISA Evaluation of charge- based/non-specific binding
BVP/DNA/ Insulin ELISA
FcRn Affinity Evaluation of clearance
FcRn Affinity
Serum Stability Evaluation of half-life
Serum Stability
Sequence liability and CDR hotspot, aggregation, and immunogenicity
Micro Developability Evaluation Overview
Category
Method
Purpose / Analytical Focus
Identifies potential liabilities such as PTMs, CDR hotspots, free cysteines, Fc mutations, and amino acid usage fr equen cy Predicts immunogenic risk based on structural, hydrophobicity, and free cysteine-related factors Assesses aggregation risk b ased on sequen ce similarity, MHC binding, and humani z ation
Liability
In Silico Analysis
Immunogenicity
Aggregation
AC-SINS and HIC
Measures self-interaction tendency
BVP /DNA/Insulin ELISA Human F cRn (BLI) Serum susceptibility
Evaluates charge-b ased/non-specific binding
O ff -Target /P K-Assessment
Assesses antibody clearance
Assesses serum stability and molecules’ half-life
DSF / T agg
Detects T m , T agg
Biophysical
Solubility /Vis cosity
For high-concentration molecules
D L S
Measures particle si z e and polydispersity
Intact Mass
Analy z es clipping variants
CE-MS
Determines charge variants and heterogeneity
Mass Spec
Peptide mapping Disulfide/Gl ycan
Identifies PTMs
Characteri z es disulfide bond and glycan profiles Monitors thermal stress, low pH, free z e / thaw stability Monitors thermal stress, low pH, free z e / thaw stability Monitors thermal stress, low pH, free z e / thaw stability Monitors thermal stress, low pH, free z e / thaw stability Monitors thermal stress, low pH, free z e / thaw stability
SEC
iCIEF
Forced Degradation Studies
CE-SDS (NR/R) Peptide mapping
SPR
Antibody Developability Optimization
With multiple successful cases, our team excels in developability optimization of challenging molecules. Below are select examples showcasing how our experts resolve early developability issues to enable optimal molecular properties for CMC development.
Expression
Degradation
Non-Specific Binding Elimin a ted
Increased 7-fold
Elimin a ted
Original Optimized
300
2 00
1 00
0
0.00 1
0.0 1
0. 1 1
1 0
1 00
1 000
mAb
mAb
mAb
Original
Op timi z ed
Original
Op timi z ed
Abs (nM)
Thermal Stability
Aggregation
Pharmacokinetics
Enhanced 11 °C
Increased 160 hours
Reduced
Original
Op timi z ed
Original Purity: 53.61%
Original Optimized
Optimized Purity: 94.98%
scFv
scFv
Fusion protein
About WuXi Biologics CRO Services
WuXi Biologics is a leading global CRDMO, with the R represented by our premium-quality CRO Services. With expertise in diverse drug modalities, we deliver comprehensive research services, including antibody discovery, protein production and engineering, and in vitro/in vivo testing, to seamlessly advance our clients’ molecules from concept to CMC development.
https://www.wuxibiologics.com/cro-services/ | PS_Marketing@wuxibiologics.com Drug Development Experience Empowering Research Services for Biologics
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