Micro Developability: Early Assessment of Biologics

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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