Tumor-specific cell killing by ADCs relies on target-mediated internalization and release of cytotoxic payload. CS5001 is an ADC armed with an ultra-potent pyrrolobenzodiazepine (PBD) payload to maximize cytotoxicity mediated by receptor tyrosine kinas-like orphan receptor 1 (ROR1), a tumor-specific receptor for both hematologic malignancies and solid tumors. This translational study of CS5001 aims to explore the potential of developing CS5001 in solid tumors, including the evaluation of ROR1 expression in human samples of various solid tumor, in vitro cytotoxicity and in vivo efficacy of CS5001 and their correlation with ROR1 expression, validating ROR1 expression as a potential predictive biomarker in subsequent clinical development of CS5001. The results showed that ROR1 was expressed in multiple solid tumors, and CS5001 exhibited potent cytotoxicity against both hematological and solid tumor cells expressing ROR1. CS5001 also showed significant ROR1-dependent tumor growth inhibition in mouse xenografts of solid tumors and human TNBC PDX models. CS5001 is a promising candidate drug with precision treatment potential in both hematologic tumors and malignant solid tumors.
'We are delighted to present the translational data of CS5001 at the World ADC London conference in
The global multi-regional dose finding phase I clinical trial of CS5001 has completed safety evaluation of several dose levels, with results indicating good safety and tolerability.
Previously, preclinical data of CS5001 was presented in a late-breaking abstract (LBA) session at the 33rd International Molecular Targets and Cancer Therapeutics Symposium in 2021. The data indicated that CS5001 exhibits strong selective cytotoxicity in various ROR1-expressing tumor cell lines and significant in vivo anti-tumor activity in both blood and solid tumor xenograft mouse models.
About CS5001 (ROR1 ADC)
CS5001 is now a clinical-stage antibody-drug conjugate (ADC) targeting ROR1 (receptor tyrosine kinase-like orphan receptor 1). CS5001 has uniquely designed and LCB's proprietary tumor-cleavable linker and pyrrolobenzodiazepine (PBD) prodrug. Only after reaching the tumor, the linker and prodrug are cleaved to release the PBD toxin, resulting in lethal DNA cross-links in cancer cells. The use of the linker plus PBD prodrug effectively helps addressing the toxicity problem associated with traditional PBD payloads, leading to a better safety profile.
Additionally, CS5001 utilizes site-specific conjugation for a precise drug antibody ratio of which enables homogeneous production and large-scale manufacturing.
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About CStone
CStone (HKEX: 2616) is a biopharmaceutical company focused on research, development, and commercialization of innovative immuno-oncology and precision medicines to address the unmet medical needs of cancer patients in
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