Doer Biologics Showcases DR510, a Dual-Masking EGFR T-Cell Engager Prodrug Built on the Accubody® Platform, at ESMO 2025

T-cell engagers (TCEs) face significant challenges in the treatment of solid tumors, including on-target off-tumor toxicity, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). TME-activated TCE prodrugs represent a potential strategy to address these issues.

This study reports the preclinical development of DR510, a TCE prodrug targeting EGFR independently developed by Doer Biologics. DR510 employs a proprietary cleavable substrate linker and a VHH masking domain (VHHm) derived from SP34-specific neutralizing anti-CD3 antibodies as the activity-shielding domain. Through non-covalent binding between VHHm and aCD3 scFv, the conformation of the EGFR Fab fragment can be simultaneously "locked" to achieve dual activity shielding of both the EGFR Fab and aCD3 scFv. Additionally, an albumin-binding domain (ABD) for half-life extension is fused to the N-terminus of VHHm. In the tumor microenvironment (TME), single-site cleavage activates the TCE and releases ABD-VHHm, enhancing therapeutic activity while minimizing peripheral off-target toxicity.

In all preclinical tumor models, DR510 demonstrated superior inhibition of tumor growth compared to another clinical-stage prodrug targeting the same pathway at equimolar doses (0.066~0.2 mg/kg). In cynomolgus monkey pre-toxicology studies, DR510 exhibited favorable pharmacokinetic properties and tolerability at doses of 0.65 mg/kg and 1.3 mg/kg, with only a slight increase in IL-6 observed, indicating a very low risk of CRS.

DR510 is developed based on Doer Biologics' proprietary Accubody® technology platform, which does not require screening for different shielding peptides to achieve dual shielding—a feature that distinguishes it from most previously reported TCE prodrugs. The unique dual masking design of DR510 strikes a critical balance between efficacy and safety. Based on preclinical data, DR510 is currently planned to advance into clinical translation for the treatment of EGFR-positive solid tumors.

EGFR is widely expressed in a variety of solid tumors and is a key signaling pathway mediating tumor growth and metastasis. However, there are currently no EGFR TCE drugs on the market. Given the tremendous potential of immunotherapy in the field of oncology, Doer Biologics will fully advance the clinical development of DR510, committing to the development of innovative cancer treatment solutions to meet urgent clinical needs.