AACR 2026: Dor Bio and Yantang Bio Unveil DR319-DP, a First-in-Class Bispecific Dual-Payload ADC Targeting Nectin-4/Trop-2 to Overcome Resistance and Toxicity in Solid Tumors
Doer Biologics
Biological Drug Developer
At the 2026 AACR Annual Meeting, Zhejiang Doer Biologics Co., Ltd. ("Doer Biologics") presented preclinical data for DR319-DP, a world-first Nectin-4/Trop-2 bispecific antibody dual-payload ADC developed in collaboration with Glyco-therapy Biotechnology Co., Ltd. ("Glyco-therapy Biotechnology").
Trop-2 and Nectin-4 are currently hot targets in the ADC field, but their clinical application still faces bottlenecks such as frequent drug resistance and a narrow therapeutic window. Additionally, since Nectin-4 and Trop-2 are expressed to some extent in normal skin and ocular tissues (with relatively higher expression of Trop-2), traditional ADCs targeting Trop-2 and Nectin-4 also face the challenge of on-target/off-tumor toxicity.
To address the aforementioned issues, Doer Biologics and Glyco-therapy Biotechnology Co., Ltd. have joined hands to effectively combine the "1+1" bispecific antibody architecture with the glycan conjugated dual-payload platform YT-DP, creating a new generation of bispecific antibody dual-payload ADC that boasts high specificity, high efficacy, and low toxicity: DR319-DP (Trop2/Nectin-4 bispecific antibody, TOP1i/DAR4 + MMAE/DAR2).
Schematic Diagram of DR319-DP Molecular Structure
DR319-DP Antibody: The DR319 portion of the antibody utilizes an Avidity-driven anti-Trop-2 VHH (low affinity/high avidity) combined with an anti-Nectin-4 monoclonal antibody in a "1+1" structure. This design enhances binding to Nectin-4/Trop-2 double-positive tumor cells while significantly reducing on-target/off-tumor binding to single-positive cells.
DR319 demonstrates potent endocytosis on Nectin-4/Trop2 double-positive cells and significantly outperforms Enfortumab.
DR319-DP has a similar affinity to naked DR319.
DR319-DP exhibits potent cytotoxic activity on Nectin4/Trop2 double-positive cells, while showing significantly reduced cytotoxic activity on Nectin-4 single-positive cells.
DR319DP demonstrates superior bystander killing activity compared to PADCEV.
DR319DP exhibits excellent stability in vitro.
DR319DP Exhibits Potent and Durable Antitumor Activity in Multiple Mouse Models.
In various mouse CDX and PDX models, DR319-DP demonstrated potent and durable tumor inhibition activity. At a dose of 1 mg/kg, DR319-DP achieved comparable tumor inhibition effects to PADCEV at 8 mg/kg and the combination of PADCEV at 4 mg/kg + SKB264 at 4 mg/kg. Moreover, DR319-DP showed significant advantages over ADCs conjugated with a single TOP1i payload (DR319-CPD3). Notably, a single administration of DR319-DP resulted in remarkable regression of large tumor volume tumors (TNBC PDX). Additionally, DR319-DP exhibited a longer half-life and superior pharmacokinetic properties compared to DR319-CPD3 and PADCEV in cynomolgus monkeys, rats, and immunodeficient mice (data not shown).
The poster of DR319-DP at the AACR 2026 venue attracted significant attention and interest from attendees. Dr. Junfang Xu, Chief Medical Officer of Huadong Medicine, Dr. Yi Yang, CEO of Glyco-therapy Biotechnology Co., Ltd., and Dr. Yongliang Fang, COO of Doer Biologics, presented the poster of DR319-DP on-site and engaged in in-depth discussions with participants.
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The preclinical data presented at AACR 2026 suggest that DR319DP outperforms traditional single-target or single-payload ADCs in terms of precision, efficacy, safety, and overcoming resistance, demonstrating strong clinical development potential. It is expected to become a Best-in-class dual-antibody dual-payload ADC in the field of pan-solid tumors.
About Doer Biologics
Doer Biologics focuses on innovative biopharmaceuticals such as multispecific antibodies, ADCs, and long-acting proteins. Relying on its proprietary core technology platforms, it continuously develops first-in-class/best-in-class pipelines to benefit patients worldwide.
About Glyco-therapy Biotechnology Co., Ltd.
Glyco-therapy Biotechnology Co., Ltd. focuses on the development of a new generation of multi-specificity conjugate drugs, driven by its core technology platforms: the proprietary glyco-conjugation technology platform (YTConju®), the TOP1i technology platform (YT-CLTpTM), and the dual-payload technology platform (YT-DP).