HDM2024: A novel EGFR and HER3 bispecific antibody-drug conjugate exhibits superior antitumor activity and favorable toxicological profile
Presenter: Qingyu Shu Session: Antibody-Drug Conjugates 2 Time: 4/22/2026 9:00:00 AM → 4/22/2026 12:00:00 PM
Authors
Qingyu Shu , Yan Xia , Zhaofeng Qin , Shengxing Zhao , Yang Chen , Rongrong He , Hao Pan , Hongwen Li , Dongzhou Jeffrey Liu Huadong Medicine Co., Ltd., Hangzhou, China
Abstract
Introduction: The epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) are frequently co-expressed in a variety of solid tumors and play crucial roles in driving tumor growth, therapeutic resistance, and metastasis. To overcome the limitations of single-target approaches, we developed a novel bispecific antibody-drug conjugate simultaneously targeting EGFR and HER3. Methods: HDM2024 was engineered using single-valency design, consists of a clinically validated HER3 antibody paired with an EGFR-targeting VHH antibody. The antibody was conjugated with exatecan via a cleavable linker, drug-antibody ratio (DAR) is 4. The efficacy and safety of HDM2024 were tested in xenograft and patient derived xenograft (PDX) models and monkeys, respectively. Results: HDM2024 was designed with balanced affinity towards EGFR and HER3 antigen. In vitro, HDM2024 demonstrated high-affinity binding to both EGFR and HER3 expressing tumor cells, efficient internalization, and potent cytotoxicity across a panel of cancer cell lines with varying expression levels of EGFR and HER3. In vivo, HDM2024 exhibited robust antitumor efficacy in multiple xenograft and patient-derived xenograft (PDX) models, achieving complete or durable tumor regressions at well-tolerated doses. In GLP toxicity study, HDM2024 showed favorable safety with the highest non-severely toxic dose (HNSTD) reaching up to 40mg/kg administered every 2weeks (Q2W) for three cycles. Conclusion: Collectively, these results support HDM2024 as a promising therapeutic candidate for solid cancer treatment. A differentiated ADC drug design endows HDM2024 with enhanced pharmacological efficacy and safety advantages, giving it the potential to become a best-in-class drug candidate. HDM2024 is expected to start the clinical trial in Mar 2026.
Disclosure
Q. Shu, Huadong Medicine Co., Ltd. Employment. Z. Qin, Huadong Medicine Co., Ltd. Employment. S. Zhao, Huadong Medicine Co., Ltd. Employment. Y. Chen, Huadong Medicine Co., Ltd. Employment. R. He, Huadong Medicine Co., Ltd. Employment. H. Pan, Huadong Medicine Co., Ltd. Employment. H. Li, Huadong Medicine Co., Ltd. Employment. D. Liu, Huadong Medicine Co., Ltd. Employment.
Cited in
Control: 895 · Presentation Id: 4515 · Meeting 21436