Preclinical development of ABL206, a novel bispecific antibody-drug conjugate targeting B7-H3 and ROR1.

Authors

Jung A Kwon, Suyoun Lee, Juhee Kim, Byeong Min Yoo, Hyeon Ji Park, Ilhwan Ryu, Junyoung Kim, JaeHyun Eom, Yong-Gyu Son, Donghoon Yeom, Byungje Sung, Myeonghan Yoo, Arim Seo, Jiseon Yoo, Jin Young Park, Jinwon Jung, Jinhyung Ahn, Weon-Kyoo You, Sang Hoon Lee, Min Ji Ko

Published in

mAbs. Volume 18. Issue 1. Pages 2731283. Epub Sep 12, 2026.

Abstract

Bispecific antibody-drug conjugates (BsADCs) represent a promising strategy to enhance tumor selectivity and overcome the limitations of monospecific ADCs. Here, we report the preclinical development of ABL206 (NEOK001), a novel BsADC targeting B7-H3 and ROR1, which are frequently co-expressed in various solid tumors. ABL206 was engineered in a 2 + 2 format and site-specifically conjugated with tavatecan, an exatecan-based linker-payload, utilizing GlycoConnect® technology to yield a highly homogeneous molecule with a drug-to-antibody ratio (DAR) of 4. In vitro, ABL206 demonstrated specific dual antigen binding, internalization, potent target-dependent cytotoxicity and a bystander killing effect. In vivo, ABL206 induced superior tumor regression, outperforming exact-matched monospecific ADCs at equimolar doses. Across 38 patient-derived xenograft (PDX) models spanning nine tumor types, ABL206 demonstrated broad translational potential with strong tumor regression. ABL206 consistently outperformed clinical-stage benchmark monospecific ADCs, ifinatamab deruxtecan (I-DXd) and zilovertamab vedotin, and effectively induced regression in I-DXd-pretreated regrowing tumors. Furthermore, ABL206 exhibited excellent in vitro plasma stability, a robust pharmacokinetic profile in rodents and non-human primates, and a favorable safety profile with the highest non-severely toxic dose (HNSTD) of 60 mg/kg in cynomolgus monkeys. Collectively, these data provide a comprehensive preclinical proof-of-concept for ABL206, supporting its advancement into a Phase 1 clinical trial for patients with advanced solid tumors (NCT07612176).

PMID:
42731893
Bibliographic data and abstract were imported from PubMed on 13 Sep 2026.

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