Antibody–Drug Conjugates (ADCs) such as T-DM1 rely on intracellular lysosomal degradation to release active catabolites, yet identifying these low abundance species within a complex biological matrix remains a major analytical challenge. This case study presents a systematic profiling of T-DM1 payload containing catabolites generated in human liver lysosomes, offering critical insights into the ADC’s processing pathways that directly inform efficacy, safety, and risk assessment.

Highlights

• Comprehensive Catabolite Panel: 12 distinct payload containing species identified from lysosomal digestion.
• Major Metabolite Confirmed: Lys-MCC-DM1 as the predominant catabolite, reflecting extensive proteolytic trimming.
• Novel Species Detected: Newly identified Ser-Lys-MCC-DM1 variants, showcasing analytical sensitivity.
• Actionable Mechanistic Insight: Detailed catabolite profiles support DMPK evaluation and ADC design decisions.

Download the full case study to explore how this analytical approach can strengthen your ADC programs and de‑risk candidate selection.