Bispecific ADCs: Making 1+1>2
Bispecific ADCs (BsADCs) is an innovative targeted therapy utilizing a bispecific antibody to target moiety in ADC. This allows BsADCs to simultaneously target two antigens/epitopes, potentially overcoming resistance mechanisms seen with single-target therapies and improving efficacy.
As of the 1st of April 2025, Beacon currently tracks 226 bispecific ADCs (BsADCs), representing a 54% increase from August 2024. The majority of these assets are currently in active preclinical development, and no drugs have been approved to date. This indicates substantial market potential for drug developers to strive for a leading position in bringing the first BsADCs to the market.
Target and linker/payload selection can be considered two of the paramount designs when constructing BsADCs, ultimately dictating the therapeutic efficacy and toxicity of the molecule. Of the disclosed targets for BsADCs, the majority of assets are designed to target EGFR (49), taking over HER-2. Additionally, while most of the linkers and payloads are undisclosed, we saw that 25% of BsADCs involve topoisomerase I inhibitor followed by tubulin inhibitors.
Summary of Bispecific ADCs in Clinical Trials
As of April 2025, 27 BsADCs have progressed to the clinic. Only 8 BsADCs have progressed to phase 2 and phase 3 of clinical trials, with the JSKN003 trial setting the pace, having completed dosing of the first patient with HER-2-low breast cancer in Dec 2023.
In summary, the advent of unique bispecific targeting modes has infused fresh innovation into the field of ADCs, marking a new generation of ADCs. Despite being in the early stages of development, BsADC presents a novel approach with considerable potential.
