Millennium Pharmaceuticals, Inc. (Cambridge, Massachusetts) Advances Aurora A Kinase Program

CHICAGO, June 3 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. today announced two important advancements in its Aurora A kinase program. Preliminary results from a Phase I study of MLN8054, a first- in-class, orally-administered, small molecule to the Aurora A kinase, were presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. In addition, the Company initiated a new Phase I clinical program for MLN8237, a second-generation Aurora A kinase inhibitor.

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Inhibition of the Aurora A kinase represents a novel approach to treating cancer. Aurora A kinases are required for cancer cells to divide and create tumors. In preclinical models, the inhibition of Aurora A kinases has been shown to stop the proliferation of the cells and reduce tumor growth. Aurora A kinases have been shown to be over-expressed in a variety of cancers.

"The preliminary results from the MLN8054 Phase I study validate the potential of our product candidates in this exciting area," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "Building on our early experience with MLN8054 and our enhanced understanding of the biology and chemistry of the Aurora A kinase, we have engineered MLN8237, with expectations for even better efficacy and tolerability."


Phase I Clinical Trial of MLN8054, a Selective Inhibitor of Aurora A Kinase (Abstract #3577)

Data were presented on 49 patients with advanced-stage malignancies, including colorectal and non-small cell lung cancers and sarcoma, from an ongoing Phase I trial. Preliminary findings and next steps included:

-- Once-daily oral administration was well tolerated at seven days, at which point steady-state exposure of the drug was achieved -- The only drug-limiting toxicity was predicted, off-target somnolence, which was successfully managed with a four-times-daily dosing regimen and the addition of methylphenidate; dose escalation continues -- In terms of clinical response, six patients maintained stable disease for longer than eight months, even though a maximum tolerated dose has not yet been identified -- In skin biopsies taken from patients with higher blood concentrations of MLN8054, early evidence of Aurora A kinase inhibition was observed - In particular, analysis of biopsies showed that skin cells showed evidence of mitotic arrest, which is indicative of Aurora A kinase inhibition -- When a dose is established for the four-times-daily dosing, treatment duration will be extended to 14 days to evaluate the effect of prolonged exposure to the drug

The study is being conducted to determine the dose-limiting toxicities and maximum tolerated dose of MLN8054 in advanced-stage cancer patients. Pharmacokinetics are also being measured through serial blood samples. Pharmacodynamics are being measured through serial skin biopsies to assess inhibition of Aurora A kinase.


Based on the early clinical experience with MLN8054, Millennium engineered a second-generation Aurora A kinase inhibitor, MLN8237. The Company recently initiated a Phase I trial for this new molecule. The open-label, dose- escalation study will enroll advanced-stage cancer patients and is designed to determine safety and maximum tolerated dose of this new product candidate. The Company will develop both Aurora A kinase inhibitors simultaneously to determine which one could be brought forward to pivotal trials. The Company typically develops second-generation molecules as part of its small molecule strategy.

About Millennium

Millennium Pharmaceuticals, Inc., 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's research, development and commercialization activities are focused in two therapeutic areas: oncology and inflammation. By applying its knowledge of the human genome, understanding of disease mechanisms and industrialized drug discovery platform, Millennium is developing an exciting pipeline of innovative product candidates. Millennium's website is

This press release contains "forward-looking statements," including statements about the Company's growth and development of products. Various important risks may cause the Company's actual results to differ materially from the results indicated by these forward-looking statements, including: adverse results in its drug discovery and clinical development programs; failure to obtain patent protection for its discoveries; commercial limitations imposed by patents owned or controlled by third parties; the Company's dependence upon strategic alliance partners to develop and commercialize products and services based on its work; difficulties or delays in obtaining regulatory approvals to market products and services resulting from its development efforts; product withdrawals; competitive factors; difficulties or delays in manufacturing the Company's products; government and third-party reimbursement rates; the commercial success of VELCADE(R) (bortezomib) for Injection and INTEGRILIN(R) (eptifibatide) Injection; achieving revenue consistent with internal forecasts; and the requirement for substantial funding to conduct research and development and to expand commercialization activities. For a further list and description of the risks and uncertainties the Company faces, see the reports it has filed with the Securities and Exchange Commission. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.


Jennifer Snyder (media) Kyle Kuvalanka (investors)

(617) 448-0281 (857) 498-0818

Photo: Archive: http://photoarchive.ap.orgPRN Photo Desk, photodesk@prnewswire.comMillennium Pharmaceuticals, Inc.

CONTACT: Media, Jennifer Snyder, +1-617-448-0281, or Investors, KyleKuvalanka, +1-857-498-0818, both for Millennium Pharmaceuticals, Inc.

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