full-length DAR4 antibody-drug conjugate

A full-length DAR4 antibody-drug conjugate (ADC) is a therapeutic construct consisting of a complete monoclonal antibody (typically an IgG) linked to a cytotoxic payload with an average drug-to-antibody ratio (DAR) of 4. In the context of the ALM-502 development program by Almac Discovery, this specific ADC format was utilized as a benchmarking comparator to evaluate the performance of ALM-502, which features a smaller antibody architecture and a DAR of 2. The DAR4 ADC used in these studies targets the developmental proteins ALPP (placental alkaline phosphatase) and ALPPL2 (placental-like alkaline phosphatase 2), which are overexpressed in various solid tumors including gastric, pancreatic, ovarian, and bladder cancers. Preclinical data presented at AACR 2026 indicated that the full-length DAR4 ADC was less effective than the optimized ALM-502 design in terms of tumor penetration and anti-tumor efficacy in xenograft models when compared on a payload-equivalent basis.