Taiho Pharmaceutical Co. Ltd., the developer of the first orally available fluorouracil (FU) Chemotherapeutic treatment (TS-1/S-1), is presenting early stage data for eight novel oncology compounds, including potential first-in-class therapies. The data being presented during the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland underscore Taiho’s steadfast commitment to improving cornerstone anti-metabolic cancer agents and developing novel molecular targeted therapies that can be used alone or in combination worldwide.
“The data being presented demonstrate Taiho’s ability to develop novel molecular targeted agents as well as next generation cytotoxic therapies, and underscore our continued commitment to developing investigational anticancer drugs that have the potential to improve treatment options available to cancer patients,” says Masayuki Kobayashi, Taiho Pharmaceutical’s president. “Our strategy surrounding innovative research and clinical development reinforces Taiho’s pursuit of becoming a top-ten oncology company in the next decade.”
Preclinical results being presented at the EORTC-NCI-AACR Symposium show that the TAS-102 antitumor agent exhibited marked tumor growth delay after drug treatment due to FTD incorporation into DNA when evaluated using a well-recognized animal model for breast cancer, and a survival benefit in a colon cancer model.
A Phase II study of TAS-102, conducted in Japan, demonstrated an improvement in overall survival of patients with metastatic colorectal cancer. Taiho took the encouraging results from this Phase II study and completed the required western Phase I studies to initiate a global Phase III program within a 15 month period.
Exploring New Treatment Options – Alone and in Combination
Highlights of the preclinical results of Taiho’s investigational drugs being presented at the EORTC-NCI-AACR Symposium include:
--TAS-114, a first-in-class dUTPase (deoxyuridine 5’-triphosphate nucleotidehydrolase) and DPD (dihydropyrimidine dehydrogenase) dual inhibitor, was evaluated in three preclinical data sets in combination with a capecitabine-based chemotherapy as well as with S-1, and showed an impact on key pathway regulation and improvements in cytotoxicity of FU in vitro. Phase I studies are underway to explore the use of TAS-114 in combination with capecitabine, and separate studies examining the compound in combination with S-1. TAS-114 is being developed for potential use in treating solid tumors.
--TAS-115, a dual inhibitor of hepatocyte and vascular endothelial growth factor receptors, suppressed prostate cancer cell proliferation and osteoclast differentiation following bone resportion. Additionally, the combination of hepatocyte growth factor receptor gene expression signature and hepatocyte growth factor may represent a promising therapeutic biomarker for TAS-115. Taiho is developing TAS-115 as a potential treatment for solid tumors, and a Phase I study is underway.
--TAS-116, a HSP90 inhibitor, showed a high tumor/retina concentration ratio that may be important in minimizing ocular toxicity, which is a known class effect of this class of agents.
--TAS-117, an AKT inhibitor, in combination with taxanes, enhanced apoptosis induction and exhibited synergistic antitumor activity in in vitro and in vivo models.
--TAS-2104, a highly selective Aurora A inhibitor, was found to enhance anti-proliferation activity by taxanes, suggesting that the compound is suitable to test clinically in combination with taxanes.
--TAS-2913, a mutant-selective epidermal growth factor receptor inhibitor, was studied in vitro and findings suggest it may represent a new therapeutic option in the treatment of non-small cell lung cancer that is resistant to epidermal growth factor receptors and tyrosine kinase inhibitors.
--TAS-2985, a small molecule inhibitor of fibroblast growth factor receptors (FGFRs), demonstrated strong tumor growth inhibition in animal xenograft models, and a pharmacodynamic assay suggested the compound inhibits FGFR activity selectively in a human tumor xenograft model. Additionally, in vitro, the molecule selectively inhibited growth of human cancer cell lines in a FGFR-dependent manner.