DM001 is a bispecific antibody-drug conjugate (ADC) designed to treat solid tumors by targeting both TROP2 and EGFR receptors. The bispecific antibody was assembled using common light chain antibodies produced by RenLite, a fully human antibody mouse originate from Biocytogen. Its monoclonal antibody structure facilitates easy purification and drug conjugation. The structure of bispecific DM001 is a monoclonal antibody with common-light chain, based on the Biocytogen RenLite® Platform, which is stable with high purity. The Linker-Payload of DM001 is named as BLD1102 (topoisomerase inhibitor, TOPi), as described in the following figure.
Briefly, BLD1102 is a new ADC platform developed by Biocytogen independently. BCPT02 is a novel topoisomerase 1 inhibitor with broad-spectrum and potent tumor killing ability. The uniquely designed cleavable linker has excellent hydrophilicity, the hydrophilic properties of ADC is comparable with monoclonal antibody, which greatly improves the physicochemical properties of the ADC. BLD1102-ADC exhibits high stability in plasma and high tumor killing efficacy, making it an excellent next-generation ADC technology platform.
1.TROP2 x EGFR bispecific antibody (DM001 unconjugated, DM001 unconj. for short) showed continuous binding on hTROP2 and hEGFR antigens of DM001 via SPR. Binding affinity
Figure 1. Continuous binding on hTROP2 and hEGFR antigens of DM001 via SPR.
2. DM001 unconj. has superior endocytosis activity over monovalent antibodies in antigen double-positive NCI-H292 cancer cells.
Figure 2. Internalization of DM001 BsAb on NCI-H292 cells measured by Incucyte.
3.DM001 showed outstanding tumor inhibition in CDX models.
Figure 3. DM001 induced dose-dependent tumor inhibition in NSCLC CDX（B-NDG + A431）model.
4.DM001 showed outstanding tumor inhibition in PDX models.
Figure 4. DM001 induced showed robust anti-tumor effect in various PDX models.
5.DM001 has excellent hydrophilicity
Figure 5. DM001 bsAb conjugated to BLD1102 with DAR4 and DAR8, then characterised using SEC-HPLC for determine aggregation and HIC-HPLC/RP-HPLC for determine hydrophilicity.
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