Antibody Developability Assessment | Abzena

Developability Assessment

Four pillar approach – specificity, functionality, safety and manufacturability

Abzena’s assessment is based on multiple readouts that capture the fundamental characteristics of successful drug design: specificity, functionality, safety and manufacturability.

Developability assessment can severely reduce the time and expenditure required to take multiple lead candidates through expensive cell line development and manufacturing runs when the molecule has inherent liabilities. Failure to identify inherent risks early in a molecule’s development can cost a company millions of dollars in wasted expenditure when many of the liabilities can be engineered out or managed if identified early.

Abzena’s approach to developability assessment is based around the typical drug development stages of Discovery, Selection, Optimization and Development/Manufacture. Providing high throughput in silico assessment during the early stages to comprehensive in vitro and in vivo studies at later stages.

Below is a guide to the assessment done at each stage, however every molecule is different, and assessment is tailored to the molecule.

Stage I – Candidate Discovery

Assessment of 20-50 leads following Antibody Discovery

High throughput in silico and in vitro screening that identifies candidates that may be difficult to express, are unstable or hard to manufacture

Specificity

  • Assessment of mouse / NHP Cross Reactivity (Flow, Biacore, ELISA)
  • Binding to closely related family members

Functionality

  • Assessment of binding by Octet, Biacore, ELISA, HTRF or flow cytometry
  • Activity in high throughput cell-based functional assays

Safety

  • In silico assessment of potential for immune response

Manufacturability

  • In silico assessment combining primary sequence analysis and homology modelling to provide contextual identification of post translational modifications

Stage II – Candidate Design & Ranking

Assessment of typically 5-20 variants during design

Comprehensive assessment of molecule’s safety, manufacturability and other liabilities. Provides a comprehensive ranked report to give a clear picture of which molecules should be taken forward.

Specificity

  • Assessment of mouse / NHP Cross Reactivity (Flow, Biacore, ELISA)
  • Binding to closely related family members

Functionality

  • Binding to soluble antigen by Octet or Biacore, or to cells by flow cytometry
  • Cell-based or biochemical functional assays
  • Fc-mediated e.g. Fc γ, C1q, FcγR

Safety

  • In silico software used during design phase to minimise the presence of T-cell epitopes

Manufacturability

  • Expression information
  • Aggregation
  • Charge Variance
  • Thermal stability with UNcle biostability platform

Stage III – Lead Selection

Assessment of 2-5 leads and benchmarking against clinically-relevant molecules

Detailed in vitro tests with clinical comparators and assess how molecules may perform with clinical relevance

Specificity

  • Per customer requirements (e.g. early IHC/tissue cross-reactivity)

Functionality

  • Binding to soluble antigen by Biacore or to cells by flow cytometry
  • Complex cell-based or biochemical functional assays
  • Fc functional assays

Safety

  • EpiScreen™ immunogenicity assessment & Cytokine Screen™

Manufacturability

  • Stability assessment
    • Freeze thaw
    • Forced deamidation & oxidation
    • Mechanical/shear stress
  • Pre-formulation assessment
    • Thermal stability
    • Aggregation propensity
    • Subvisible particle analysis

Stage IV – Cell Line Development

Assessment of 1-2 lead molecules progressing through Cell Line Development

Specificity

  • Per customer requirements

Functionality

  • Target-mediated:
    • Binding to soluble antigen by Biacore or to cells by flow cytometry
    • Complex cell-based or biochemical functional assays

Safety

  • Assess impact of different formulations on immunogenicity

Manufacturability

  • Critical quality attributes
  • Formulation development
    • Evaluate impact on functional & safety parameters
    • Buffer, pH and ionic strength
    • Excipient screening & compatibility
    • Storage temperature

Developability for Antibody Drug Conjugates

Abzena can also evaluate ADCs for specific developability issues such as internalisation, DAR, serum stability, release kinetics, cell viability, MoA, bystander effect, drug resistance and tissue metabolomics.

shutterstock_143646112A Flexible Approach

Abzena will work with each customer to identify the right set of assays and analytics to evaluate their drug candidate. Abzena have worked with 100s of candidates, so have the expertise to help guide your approach. The developability assessment uses an FTE model which provides a flexible way to guide the assessment as the results come in, allowing more in-depth analysis or removal of superfluous analysis as necessary, without having to re-negotiate contracts.

To get more information or to schedule a teleconference please contact us.

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