Ascentage Pharma announced that the latest results from three preclinical studies of the company's novel drug candidates olverembatinib, MDM2-p53 inhibitor alrizomadlin, FAK/ALK/ROS1 tyrosine kinase inhibitor APG-2449, and EED inhibitor APG-5918, have been selected for presentations at the 2024 American Association of Cancer Research Annual Meeting (AACR 2024). These three preclinical abstracts from Ascentage Pharma include: Olverembatinib, a novel multikinase inhibitor, demonstrates superior antitumor activity in succinate dehydrogenase (SDH)-deficient neoplasms - Results from this preclinical study show that in SDH-deficient cancer cells, olverembatinib has superior efficacy compared to other approved tyrosine kinase inhibitors. Mechanistically, olverembatinib can exert its antitumor effects in SDH-deficient neoplasms by modulating multiple signal pathways involved in cell hypoxia, angiogenesis, proliferation, and survival.

These results provide a scientific rationale for the future development of olverembatinib in SHD-deficient cancers with an urgent unmet medical need. Embryonic ectoderm development (EED) inhibitor APG-5918 (EEDi-5273) and MDM2 inhibitor alrizomadlin (APG-115) synergistically inhibit tumor growth in preclinical models of prostate cancer (PCa): Results from this preclinical study show that in preclinical models of PCa, targeting both EED and MDM2 can synergistically enhance antitumor activities by modulating pathways related to DNA methylation, cell cycle, and apoptosis. These findings provide a scientific rationale for the future clinical development of APG-5918 in combination with alrizomadlin for the treatment of PCa.

APG-2449, a novel focal adhesion kinase (FAK) inhibitor, inhibits metastasis and enhances the antitumor efficacy of PEGylated liposome doxorubicin (PLD) in epithelial ovarian cancer (EOC): Results from this preclinical study show that the novel FAK inhibitor APG-2449 can reduce the metastasis of tumor cells and achieve synergistic antitumor effects with PLD in xenograft mouse models of ovarian cancer. These results support the future clinical development of APG-2449 in combination with PLD for the treatment of ovarian cancer.