NL019: A next-generation TROP2/NECTIN4 dual-target nanobody-based ADC developed from the NanoOne™ Platform
Presenter: Yu Zhang, MD;MS;PhD Session: Antibody-Drug Conjugates and Linker Engineering 1 Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Meiguang Xiong , Binbin Wang , Jie Ni , Chenchen Lu , Fang Yu , Yu Zhang Naliean Therapeutics Co. Ltd, Suzhou, China
Abstract
Background: While antibody-drug conjugates (ADCs) have transformed oncology treatment, conventional IgG-based ADCs are constrained by suboptimal tumor penetration, heterogeneous antigen expression, and Fc receptor-mediated immune toxicity. NanoOne™, developed by Naliean Therapeutics, is an innovative nanobody-based modular ADC platform that redefines ADC engineering through molecular miniaturization, structural precision, and payload flexibility. Methods: NanoOne™ integrates multiple VHH nanobody modules ( Results: NL019, a TROP2/NECTIN4 dual-target ADC armed with a microtubule inhibitor, demonstrated potent and synergistic activity in vitro—including dual-target binding, internalization, and cytotoxicity—while minimizing on-target toxicities seen in single-target ADCs. In multiple xenograft and CDX models, NL019 achieved superior, dose-dependent antitumor efficacy versus benchmark ADCs targeting TROP2 or NECTIN4. Conclusions: NL019 exemplifies the disruptive potential of NanoOne™, combining advanced molecular architecture, precision one/dual-payload conjugation, and superior tumor selectivity. Supported by strong preclinical efficacy and developability, NL019 is advancing toward first-in-human trials. Given the broad expression of TROP2 and NECTIN4 across epithelial malignancies, NL019 has the potential to establish a new generation of broad-spectrum ADC therapeutics.
Disclosure
M. Xiong, None.. B. Wang, None.. J. Ni, None.. C. Lu, None.. F. Yu, None.. Y. Zhang, None.
Cited in
Control: 1585 · Presentation Id: 5349 · Meeting 21436