1999


From: Noonan/Russo Communications

Millennium and the Whitehead Institute identify novel protein important in fat absorption

Discovery of Potential Target for Improved Obesity Therapeutics Described in the Cover Article of Molecular Cell

Cambridge, Mass., September 24, 1999 -- Millennium Pharmaceuticals, Inc (Nasdaq: MLNM) and the Whitehead Institute for Biomedical Research today announced the discovery of a novel protein involved in fat absorption. Data relating to the identification and function of the protein appear in today's issue of the journal Molecular Cell. The protein, FATP4, plays a role in transporting fatty acid molecules from the intestine into the body. Inhibition of the protein's function may provide new approaches to treating obesity.

The data, described in a paper titled "Identification of the major intestinal fatty acid transport protein," were generated collaboratively by scientists at Millennium and in the laboratory of Dr. Harvey F. Lodish at the Whitehead. FATP4 is a member of a family of fatty acid transport proteins and is expressed at high levels in enterocytes, a cell-type found in the intestinal lining. The addition of human FATP4 to cells in which the protein is not normally expressed resulted in a large increase in the uptake of fatty acids. Inhibition of FATP4 with anti-sense oligonucleotides in a mouse enterocyte cell-culture model produced a proportional reduction in the uptake of these fatty acid molecules.

"The transport of fatty acids from the intestines into the body is a key step in the absorption and metabolism of dietary fat and its conversion to body fat," said Lou Tartaglia, Ph.D., senior director of metabolic disease at Millennium. "The identification of the intestinal fatty acid transport protein provides new insight into the molecular and biochemical pathways involved in the transport and utilization of dietary fat," added Tartaglia.

"Previously, our laboratory had identified a novel class of proteins called FATPs, which are associated with fatty acid transport proteins," said Dr. Harvey F. Lodish of the Whitehead Institute. "To date we have identified five of these proteins in mice and six in humans. FATP4 expression is very high in enterocytes, while other members of the family are expressed in other tissues. We are excited about the potential therapeutic impact of this gene discovery."

"The discovery of FATP, which is currently in small molecule drug discovery at Millennium, has great promise as a target for new obesity therapeutics," said Ruth Gimeno, Ph.D., FATP project leader at Millennium.

Millennium and the Whitehead have filed joint patents on the fatty acid transporters, including FATP4. Millennium has exclusively licensed the rights to the FATP4 gene and to the other members of the FATP family identified by Dr. Lodish and his colleagues. The company intends to continue development of FATP4 using internally available resources while it evaluates potential partnership opportunities for its robust pipeline of obesity targets.

"The most widely prescribed obesity drug on the market today blocks an earlier step in the process of absorbing dietary fat," said Robert Tepper, M.D., chief scientific officer of Millennium. "It is possible that therapeutic approaches based on blocking the function of FATP4 may be more efficacious and may mitigate certain unpleasant side effects associated with the currently available drug," Dr. Tepper added.

In the United States, more than one half of adults--97 million people--are overweight or obese, according to the U.S. National Institutes of Health. Human obesity greatly increases the risk for the development of diabetes, heart disease, high blood pressure and stroke.

The authors of the paper are as follows:

    Andreas Stahl, Whitehead Institute for Biomedical Research
    David J. Hirsch, Whitehead Institute for Biomedical Research
    Ruth E. Gimeno, Millennium Pharmaceuticals, Inc.
    Sandhya Punreddy, Millennium Pharmaceuticals, Inc.
    Pei Ge, Millennium Pharmaceuticals, Inc.
    Nicki Watson, Whitehead Institute for Biomedical Research
    Shraddha Patel, Whitehead Institute for Biomedical Research
    Mariana Kotler, Whitehead Institute for Biomedical Research
    Alejandra Raimondi, Millennium Pharmaceuticals, Inc.
    Louis A. Tartaglia, Millennium Pharmaceuticals, Inc.
    Harvey Lodish, Whitehead Institute for Biomedical Research

Millennium, a leading drug discovery and development company, employs large-scale genetics, genomics, high throughput screening and informatics in an integrated science and technology platform. This innovative drug discovery platform is applied across the entire healthcare sector, from gene identification through patient management, to accelerate and transform the discovery and development of proprietary therapeutic and diagnostic products and services. Headquartered in Cambridge, Massachusetts, Millennium and its affiliates currently employ more than 800 people.

This press release contains forward-looking statements that involve a number of risks and uncertainties. Among the factors that could cause actual results to differ materially from those indicated in such forward looking statements include uncertainties relating to gene identification, drug discovery and clinical development processes; changes in relationships with strategic partners and dependence upon strategic partners for the performance of critical activities under collaborative agreements; the impact of competitive products and technological changes; uncertainties relating to patent protection and regulatory approval; and uncertainties relating to the ability of Millennium and its affiliates to obtain the substantial additional funds required for progress in drug discovery and development. The factors that could affect Millennium's performance are more fully described in filings by Millennium with the Securities and Exchange Commission including but not limited to the factors set forth under the heading "Business - Factors That May Affect Results'' in the Annual Report on Form 10-K of Millennium for the year ended December 31, 1998 as filed on March 24, 1999.

Editor's Note: This release is available on Millennium's home page at: http://www.mlnm.com




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