Abstract 227: BPRDP056, a novel small molecule drug conjugate specifically targeting phosphatidylserine for cancer therapy

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Zinc(II)-dipicolylamine (Zn-DPA) have been described to specifically complex with phosphatidylserine (PS), which has a higher level at the external surface of cancer cells in tumorigenic condition. BPRDP056 is a Zn-DPA-SN38 conjugate designed to provide a PS-targeting drug delivery of cytotoxic payload SN-38 at the tumor microenvironment, thereby, decrease the dosage of SN38, while induce apoptosis in cancer cells. The in vivo therapeutic efficacy of BPRDP056 against the growths of human tumors has been shown significant in mice subcutaneously bearing a tumor type of pancreas, prostate, colon, liver, breast and glioblastoma, as well as in mice with an orthotopic pancreatic tumor. BPRDP056 shrunk tumors at a lower dosing intensity (~20%) of SN38 compared to CPT-11 in all models tested. Micro-Western assays showed that BPRDP056 exhibited apoptotic cell death signal levels similar to those of CPT-11 in the treated tumors in mice. Furthermore, pharmacokinetic and preliminary toxicology studies showed that BPRDP056 has a good stability in circulation with an acceptable therapeutic safety window in mice. BPRDP056 has been demonstrated with a tumor targeting ability and thus increases the cytotoxic payload SN38 concentration in situ for improved efficacy. Its therapeutic spectrum against malignant neoplasm will be expected to cover the PS-rich tumor microenvironment of all cancer types. BPRDP056 is a first-in-class Small Molecule Drug Conjugate for anti-cancer therapy.Citation Format: Chia-Yu Hsu, Yun-Yu Chen, Chen-Fu Lo, Tai-Yu Chiu, Ching-Ping Chen, Chen-Lung Huang, Chung-Yu Huang, Min-Hsien Wang, Yu-Sheng Chao, Joe C. Shih, Teng-Kuang Yeh, Lun K. Tsou, Chiung-Tong Chen. BPRDP056, a novel small molecule drug conjugate specifically targeting phosphatidylserine for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 227.

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