trastuzumab bromoseradeg / Fortitude Biomedicines - LARVOL DELTA

A novel covalent BRD4 degrader-HER2-targeting antibody-drug conjugate (DAC) overcomes trastuzumab deruxtecan resistance in HER2-positive cancers (AACR 2026) - "Trastuzumab bromoseradeg (T-BsD) was synthesized by cysteine conjugation chemistry via the cleavable Valine-Citrulline-para-aminobenzyl carbamate (Val-Cit-PABC; VCP) linker with an average drug-to-antibody ratio (DAR) of ~4. By integrating potent BRD4 degradation with HER2-targeted delivery, T-BsD achieves superior activity and effectively bypasses the two most clinically relevant T-DXd resistance pathways. Together, these data strongly support the selective BRD4 degrader as a promising payload for developing next-generation ADCs that can benefit patients who are refractory or resistant to current ADC therapies."

ADC • Oncology • ABCC1 • BRD4 • TOP1