Micro Developability: Early Assessment of Biologics

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)

[bu„er*](3,7) [bu„er*](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 450 nm

10 12

Eculizumab Ganitumab Tremelimumab Vesencumab

0 2 4 6 8

0

0.4

2

10

50

250

mAb Concentration (µg/mL)

Differential Scanning Fluorimetry (DSF) Assay • Measures melting temperatures and predicts 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 (°C)

Temperature (°C)

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

5-1-2024

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