Doer Biologics Presents Preclinical Data of DR319-DP, a Bispecific Dual-Payload ADC Targeting Nectin-4 and Trop-2, at AACR 2026

DR319：Nectin-4/Trop-2 bispecific ADC

Despite the fact that Trop-2 and Nectin-4 are highly promising targets for the new generation of antibody-drug conjugates (ADCs), the emergence of drug resistance,"Toxicity triggered by both 'off-target/off-tumor' and 'on-target/off-tumor' effects remains an urgent issue."Solving Key Treatment Challenges. To maximize antitumor activity while reducing systemic toxicity and broadening the therapeutic window, this study developed a "1+1" configuration, Avidity-driven bispecific antibody—DR319, featuring a monovalent low-affinity binding arm targeting Trop-2 VHH. This design enables potent binding to Nectin-4/Trop-2 double-positive tumor cells while minimizing binding to single-positive cells, thereby reducing peripheral toxicity.

We conjugated DR319 with a novel linker-topoisomerase I inhibitor (TopoI) payload CPD3 to obtain DR319-CPD3. In mouse models, DR319-CPD3 demonstrated superior anti-tumor effects compared to single-target ADCs. Additionally, this study constructed a dual-payload ADC-DR319-DP based on the glycoconjugation dual-payload platform (YT-DP). DR319-DP employs a payload combination of a topoisomerase I inhibitor (TopoI) with a DAR value of 4 and a microtubule inhibitor (MTI) with a DAR value of 2. In preclinical studies, the dual mechanism of action (MOA) payloads of DR319-DP achieved stronger and more sustained tumor inhibition than single-target/single-payload benchmark ADCs across various CDX and PDX tumor models. These preclinical results strongly support the clinical development of the DR319 series ADCs, which are expected to become potential best-in-class drugs for solid tumor treatment.