As a core technological trajectory for next-generation precision cancer therapies, dual-payload antibody-drug conjugates (ADCs) hold significant promise to resolve the clinical limitations of conventional single-payload ADCs. However, CMC development of dual-payload ADCs is widely recognized within the industry as exceptionally challenging, with core technical barriers concentrated in four critical dimensions: elevated chain mispairing and conjugation complexity for KIH-based BsAb-ADCs, aggravated payload-driven aggregation, strict DAR uniformity demands relying on coordinated expression-conjugation, and complicated analytical separation of overlapping dual-payloads/bispecific impurities.

Leveraging our accumulated expertise in ADC development and integrated technology platforms , Altruist has resolved the end-to-end development bottlenecks associated with dual-antibody dual-payload ADCs. In this whitepaper, we share the core technical barriers and control strategies for dual-payload ADCs, a KIH bispecific antibody dual-payload ADC case study, and our comprehensive quality control (QC) and in-process control (IPC) system to ensure the safety and efficacy of final drug products.