Millennium Presents New Data on Investigational Drugs for Novel Cancer Targets at EORTC-NCI-AACR Symposium
CAMBRIDGE, Mass., Oct. 22 /PRNewswire/ — Millennium: The Takeda Oncology Company today announced new data from early non-clinical studies of Millennium/Takeda-discovered pipeline molecules highlighting novel therapeutic pathways in oncology. MLN4924 data build on the growing body of evidence supporting the importance of the Millennium-discovered Nedd8 Activating Enzyme (NAE) in tumor growth and survival. It is a first-in-class small molecule inhibitor of NAE. Both clinical and non-clinical studies of MLN8237 confirm the importance of inhibiting Aurora A kinase, which is required for cells to proceed through cell division.
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TAK-285 and TAK-593 are receptor tyrosine kinase inhibitors. Non-clinical data suggest their efficacy in affecting the Epidermal Growth Factor Receptor / Human Epidermal Growth Factor Receptor (EGFR/HER) and Vascular Endothelial Growth Factor/Platelet Derived Growth Factor (VEGF/PDGF) pathways, respectively. The data from 21 Millennium abstracts were presented at the 20th EORTC-NCI-AACR* Symposium on “Molecular Targets and Cancer Therapeutics” held October 21 to 24 in Geneva, Switzerland.
“These new data demonstrate the potential of novel pathways and innovative approaches to existing pathways that will further oncology research,” said Nancy Simonian, M.D., Chief Medical Officer, Millennium. “Early results such as these demonstrate our oncology expertise in advancing both the current Millennium oncology molecules and those we are integrating into our pipeline from Takeda.”
MLN4924 is a first-in-class small molecule inhibitor of NAE, a new target discovered by Millennium scientists. Data from two non-clinical studies showcased at EORTC highlight its potent activity in inducing apoptosis, or programmed cell death, in cultured human tumor cells and human tumors grown in mice.
MLN4924 advanced to clinical trials with the first patient dosed in April 2008. The two Phase I dose escalation studies aim to assess safety, tolerability, pharmacokinetic and pharmacodynamic effects in patients with advanced solid tumors or with hematological malignancies.
-- Pharmacodynamic and efficacy relationship of MLN4924, a novel small molecule inhibitor of Nedd8-activating enzyme, in human xenograft tumors grown in immunocompromised mice -- Lead investigator: Allison Berger, Senior Scientist, Millennium -- Abstract #85: Poster -- MLN4924, a potent and novel small molecule inhibitor of Nedd8 activating enzyme, induces DNA re-replication and apoptosis in cultured human tumor cells -- Lead investigator: Michael Millhollen, Scientist, Millennium -- Abstract #356: Poster MLN8237
This Millennium-discovered Aurora A kinase inhibitor currently is being studied in Phase I trials in adults both in the United States and Spain. Millennium plans to expand the MLN8237 program into Phase II trials in late 2008/early 2009.
Researchers also are investigating MLN8237 as a potential oral single-agent therapy for children with either relapsed acute lymphoblastic leukemia (ALL) or advanced neuroblastoma-two pediatric cancers that are difficult to treat. In October 2008, the first pediatric patient was dosed with MLN8237 in a clinical trial conducted by the Children’s Oncology Group (COG).
New MLN8237 clinical data about safety, dosing, pharmacokinetic and pharmacodynamic results in adults, along with preclinical data about activity in tumor models of pediatric malignancies, were presented at EORTC.
-- MLN8237, an oral selective Aurora A kinase inhibitor: initial results of dose-finding pharmacokinetic-pharmacodynamic Phase I study -- Lead investigator: J. Tabernero Caturla, Hospital Universitario Vall d'Hebron, Barcelona, Spain -- Abstract #285: Poster -- Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MLN8237, a selective Aurora A kinase inhibitor, in the United States -- Lead investigator: Jeffrey R. Infante, M.D., Investigator, Drug Development & GI Cancer Research, Sarah Cannon Research Institute, Nashville, Tennessee -- Abstract #280: Poster -- Pediatric Preclinical Testing Program (PPTP) stage 2 testing of the Aurora A kinase inhibitor MLN8237 -- Lead investigator: Malcolm Smith, M.D., Ph.D., Associate Chief, Pediatric Oncology, Cancer Therapy Evaluation Program, National Cancer Institute -- Abstract #286: Poster TAK-285
TAK-285 is a novel EGFR/HER dual kinase inhibitor that is being studied in Phase I trials in adults both in the United States and Japan. New TAK-285 non-clinical data presented at EORTC suggest good target specificity, favorable pharmacokinetics and tumor distribution, efficacy in EGFR- and HER2-expressing xenograft models, activity in tumors harboring activated RAS or inactivated LKB1 mutations and activation of AMPK pathways in cardiac cells.
-- Tyrosine kinase inhibitors, such as TAK-285, GW572016 or SU11248, protect or damage the heart based on their ability to activate AMPK -- Lead investigator: S.A. Shell, Targeted Molecular Diagnostics, Research and Development, Westmont, Illinois -- Abstract #78: Poster -- In vivo antitumor efficacy of TAK-285, a novel ErbB1/ErbB2 dual kinase inhibitor -- Lead investigator: A. Iwahara, Takeda Pharmaceutical Company, Japan -- Abstract #311: Poster -- Novel inhibitory mechanisms of TAK-285, a new EGFR/ErbB2 dual inhibitor -- Lead investigator: S.A. Shell, Targeted Molecular Diagnostics, Research and Development, Westmont, Illinois -- Abstract #313: Poster -- Combined antitumor efficacies of TAK-285, a novel ErbB1/ErbB2 dual kinase inhibitor, with other anticancer drugs -- Lead investigator: T. Tamura, Takeda Pharmaceutical Company, Japan -- Abstract #314: Poster TAK-593
TAK-593 is a novel small molecule selective inhibitor of the tyrosine kinases for the VEGF and PDGF receptor families. New non-clinical TAK-593 data presented at EORTC show potent pseudo-irreversibility against VEGF2 and PDGFbeta.
-- Unique enzymatic profile of a potent and selective BEGFR/PDGFR tyrosine kinase inhibitor, TAK-593: potent pseudo-irreversibility against VEGFR and PDGFR -- Lead investigator: H. Miki, Takeda Pharmaceutical Company, Japan -- Abstract #50: Poster -- TAK-593, a potent and selective VEGFR/PDGFR tyrosine kinase inhibitor, effects the tumor vascularity and vascular permeability -- Lead investigator: A. Hori, Takeda Pharmaceutical Company, Japan -- Abstract #51: Poster -- In vivo profiles of a novel compound, TAK-593, a highly potent and selective inhibitor against VEGF and PDGF tyrosine kinases -- Lead investigator: A. Mizutani, Takeda Pharmaceutical Company, Japan -- Abstract #56: Poster About Millennium
Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a novel cancer product, and has a robust clinical development pipeline of product candidates. Millennium was acquired by Takeda Pharmaceutical Company Ltd in May, 2008. The Company’s research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website, http://www.millennium.com/.
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Millennium: The Takeda Oncology Company
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