Developability assessment for monoclonal antibody drug candidates: a case study

Area of Science:

• Biopharmaceutical Development
• Protein Chemistry
• Drug Discovery

Background:

• Industry screening evaluates risks for drug candidates, complicated by biological therapeutics like monoclonal antibodies (mAbs).
• Early assessment of drug-like properties (DLP) is vital for cost and time efficiency in developing stable drug products.
• Monoclonal antibody derivatives and complex constructs present unique development challenges.

Purpose of the Study:

• To present a case study on screening four IgG1 mAbs with variable domain sequence variations for drug-like properties.
• To evaluate the utility of a comprehensive, tiered analytical approach for assessing molecular and stability characteristics.
• To identify potential development challenges early in the drug discovery process.

Main Methods:

• Employed a comprehensive, tiered analytical approach using multiple tools.
• Assessed molecular characteristics, conformational stability, colloidal stability, and short-term storage stability.
• Investigated a specific mAb (mAb-2) with adverse colloidal properties across an expanded pH range.

Main Results:

• Most drug-like properties for the four IgG1 mAb candidates were comparable and acceptable.
• mAb-2 exhibited unfavorable colloidal properties, including a propensity for phase separation at specific pH values.
• The comprehensive DLP assessment identified a need for additional development efforts for mAb-2.

Conclusions:

• Comprehensive DLP assessments, particularly across an expanded pH range, are beneficial for identifying development challenges.
• This adaptable screening approach aids in selecting promising molecules with potential stability issues.
• The methodology is particularly valuable for the development of complex antibody constructs and biotherapeutics.