BSI-04702 / Biosion, OBI Pharma - LARVOL DELTA

In vitro characterization of a novel TROP2-targeting antibody-drug conjugate OBI-992 (AACR 2024) - "Sacituzumab govitecan, a TROP2 ADC conjugated to topoisomerase inhibitor (TOP1) SN-38, has been approved for patients with triple-negative breast cancer. This study aims to investigate the characteristics of a novel TROP2 antibody (R4702) and its ADC OBI-992, which is derived from the conjugation of R4702 with a TOP1 inhibitor exatecan.METHODSClinical study: Prognostic roles of TROP2 and TOP1 in patients were accessed through the "Kaplan-Meier plotter" database from more than 1055 colon cancer patients.In vitro study: An ELISA study was conducted to investigate the binding epitope of R4702...Finally, a synergistic effect of OBI-992 and PARP inhibitors (talazoparib, rucaparib, niraparib, and olaparib) on the enhancement of cancer cell killing and DNA damage was observed.CONCLUSIONHigh expression of both TROP2 and TOP1 is associated with poor survival in patients with colon cancer...Exatecan and exatecan-conjugated ADC OBI-992 showed high cytotoxic activities...."

ADC • Preclinical • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • TACSTD2 • TOP1

Preclinical evaluation of a novel antibody-drug conjugate OBI-992 for Cancer therapy. (PubMed, Sci Rep) - "OBI-992, an investigational TROP2-targeted ADC, is composed of a novel TROP2 antibody (R4702) conjugated to the topoisomerase I (TOP1) inhibitor exatecan through a hydrophilic enzyme-cleavable linker...ADCs sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) were used as benchmarks for OBI-992...Moreover, substantial enhancement of cytotoxicity and DNA damage was found in the combination of OBI-992 with a poly (ADP-ribose) polymerase (PARP) inhibitor (talazoparib). Taken together, the findings in this study support further clinical development of OBI-992."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • TACSTD2 • TOP1

Novel TROP2-targeted CAR T cells with high specificity and sustained efficacy for solid tumors in animal models. (ASCO 2024) - "A novel TROP2-specific R4702 CAR T cell, developed, showcased robust tumor-killing capabilities. The anti-tumor activity persisted upon repeated tumor challenges across various xenograft models, underscoring the potential of R4702 CAR T cells as a promising therapeutic strategy."

CAR T-Cell Therapy • Preclinical • Bladder Cancer • Cervical Cancer • Endometrial Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • TACSTD2