Early-stage biologics drug developability testing using <1 mg antibody completed within 2 weeks, from in silico analysis, PK prediction to biophysical analysis.
Protein Sciences: Early-stage R&D Micro Developability Package
Micro developability studies consist of a series of advanced assays conducted via high-throughput analysis to evaluate large quantities of different drug candidates. These studies allow lead molecules to be examined at earlier stages of R&D using minimal material. Most of the assays in these studies can be completed within two weeks using less than 1 mg of protein. These studies allow molecules to be screened, evaluated, eliminated, or advanced to the next candidate selection stage. For small biotech companies, these early-stage micro developability results also allow more accurate assessment and valuation of their assets.
In Silico Sequence Liability Immunogenicity Aggregation PK Prediction
In Silico Analysis
~1000
Early Stability Assessment SEC (Low pH, Freeze/Thaw) iCE (charge/pI, 40 °C) CE-SDS (NR/R) Binding&Bioassay (on cell function, 40°C)
In Silico Sequence Analysis Mass Spec Biophysical Polyreactivity/O-target/PK Predicting
~100
Biophysical DSF/DSC (Tm, Tagg) Solubility
Stability/Formulation Mass Spec
<5
Polyreactivity/Off-target/PK Predicting Human FcRn (BLI) ADCC/CDC Effector Function Binding (BLI)
Development
AC-SINS/HIC (self interaction) Baculovirus/DNA/Insulin ELISA Serum Susceptibility (Cleavage)
Assays needs <1 mg Protein Evaluate multiple molecules at early stage
Mass spec Intact: Clipping CE-MS: Charge Peptide Mapping: PTM Disulfide/Glycan
Micro Developability
Developability Study
Affinity-Capture Self-Interaction Nanoparticle Spectroscopy (AC-SINS) AC-SINS is one of the key methods to assess product stability in developability studies.
• Assessment of self-association of antibodies through wavelength shift of AuNP • Greater shift indicates higher risk of self-association/aggregation • A good prediction of aggregation/PK profile of mAbs
Non-self-associating mAb
Self-associating mAbs
400 450 500 550 0.1 0.15 0.2 0.25 0.3 0.35 0.4
400 450 500 550 0.1 0.15 0.2 0.25 0.3 0.35 0.4
[blank+2h*](3, 1) [blank+2h*](3, 2)
[atezolizumab+2h](1, 2) [atezolizumab+2h](2, 2)
[buer*](3,7) [buer*](4,7)
0.08 0.1 0.12 0.14 0.16 0.18 0.2 0.22 0.24
(536, 0.3722) (540, 0.3756) (530, 0.3801) (527, 0.3783)
(534, 0.3819)
(534, 0.2288) (530, 0.2171) (560, 0.1765)
[crenezumab+2h](1, 5) [crenezumab+2h](2, 5)
[blank+2h*](3, 1) [blank+2h*](3, 2)
[Vesencumab](3,6) [Vesencumab](4,6)
(588, 0.1738)
(560, 0.2663)
(554, 0.2604)
600 650 700 750
600 650 700 750
450
500
550
600
650
Wavelength (nm)
Wavelength (nm)
Wavelength (nm)
Low Risk
High Risk
MWD1E, Sig=280,4 Ref=o
MWD1E, Sig=280,4 Ref=o
MWD1E, Sig=280,4 Ref=o
100 110
100 110
100 110
14.075
13.912
10 20 30 40 50 60 70 80 90
10 20 30 40 50 60 70 80 90
10 20 30 40 50 60 70 80 90
8.916
14.421
14.664
15.077
15.344
12.622
15.677
12.596 12.270
8.229
2 3 4 5 6 7 8 9 1011121314151617 0
2 3 4 5 6 7 8 9 1011121314151617 0
2 3 4 5 6 7 8 9 1011121314151617 0
Time (min)
AC-SINS Associated with HIC Time (min)
Time (min)
Baculovirus/DNA/insulin ELISA • Assessment of non-specific binding of mAbs • Higher score indicates higher risk of non-specific binding • A good prediction of PK profile of mAbs • Data correlates well with DNA insulin etc. ELISA
Baculovirus ELISA 450nm
10 12
Eculizumab Ganitumab Tremelimumab Vesencumab
0 2 4 6 8
0
0.4
2
10
50
250
mAb Concentration(ug/ml)
Differential Scanning Fluorimetry (DSF) Assay • Measures melting temperatures and predict the stability and storage of antibody drugs • Lower Tm indicates lower stability of mAbs
Melt Peak
Melt Peak
40 60 20
50
0
0
-80 -60 -40 -20
-50
-100
-100
20 30 40 50 60 70 80 90
20 30 40 50 60 70 80 90
Temperature, Celsius
Temperature, Celsius
About WuXi Biologics About WuXi Biologics
Learn more: Protein Sciences: Early-stage R&D Micro Developability Package
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 | info@wuxibiologics.com
2-7-2023
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