Abstract 6751: AT2604 is a highly efficacious ADC targeting alkaline phosphatases ALPP and ALPPL2

Abstract Placental alkaline phosphatases, ALPP and ALPPL2, are highly homologous, membrane-bound proteins involved in fetal development. Despite having limited expression in normal tissues, they are highly differentiated in multiple tumor cells making them ideal targets for antibody drug conjugate (ADC) development. AT2604 is an ADC incorporating an anti-ALPP/ALPPL2 antibody conjugated to monomethyl auristatin E (MMAE) with high DAR 4 homogeneity; and displays strong tumor growth inhibition at low doses in CDX models of gastric and pancreatic cancer. In patient-derived xenograft models of gastric cancer with moderate- and low-antigen expression, AT2604 achieves near-complete tumor regression at 3 and 6 mg/kg (QWx3), respectively. A preliminary toxicity assessment in non-human primates concluded a well-tolerated dose of 10 mg/kg (Q3Wx3) without exhibiting any non-reversible adverse effects.and good plasma stability; implying that AT2604 possesses an improved safety profile over other vedotin-based ADCs. Citation Format: Bryan K.S. Yeung, Wei Qi Tan, You Xue Wu, Xi Yun Zhang, Yin Wen Cheng, Shao Jun Liu, Chen Zhong, Bin Zou. AT2604 is a highly efficacious ADC targeting alkaline phosphatases ALPP and ALPPL2​ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6751.