SITC 2023: DM001, a Novel TROP2xEGFR Bispecific ADC, Demonstrates Potent Tumor Growth Inhibition in Preclinical Models and Favorable Safety Profile in Cynomolgus Monkey
- EGFR and TROP2 are extensively co-expressed in many solid tumors, allowing dual targeting them with bsADCs.
- DM001 bsADCs simultaneous targeting both EGFR and TROP2 showed superior efficacy compared with parental single-targeting ADCs in PDX models.
- The new topoisomerase I inhibitor linker/paylopad (BLD1102) exhibits excellent hydrophilicity and is highly stable in human, monkey, and mouse plasmas and in vivo in mice.
- BLD1102 has strong bystander killing effect.
- DM001 (DM001-BLD1102) demonstrated superior anti-tumor activity to DM001-vcM MAE in PDX models, including in MMAE-resistant models.
- DM001 (DM001-BLD1102) inhibited the growth of NSCLC PDX models with or with out EGFR mutations, as well as growth of TNBC, HNSCC, CRC, ESCC and GC PDXs.
- Pilot safety study of DM001 (DM001-BLD1102) did not show general toxicities in cynomolgus monkeys. Further study is planned.
Used in the study: Bispecific ADC Platform