News Release

Millennium and Wyeth-Ayerst announce the discovery of key potassium ion channel modulating proteins

Peer-Reviewed Publication

Noonan/Russo Communications

Potential applications in therapeutic development for central nervous system disorders

CAMBRIDGE, Mass., February 3, 2000 -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM) and Wyeth-Ayerst Research, the research division of American Home Products Corporation (NYSE:AHP) today announced that they have published the identification of a family of proteins called Potassium Channel Interacting Proteins (KChIPs) that associate with and regulate the activity of certain potassium ion channels, called "A-type" channels. The study, which appears in the February 3, 2000 issue of Nature, is part of an ongoing collaboration between Wyeth-Ayerst Research and Millennium. These A-type potassium channels are thought to be involved in the control of the electrical signals of the brain and other excitable tissues. Abnormalities in the electrical signals of these tissues may form the basis for a variety of disorders including anxiety, depression, ischemia and epilepsy.

Millennium and Wyeth-Ayerst scientists believe that this paper, titled "Modulation of A-type Potassium Channels by a Family of Calcium Sensors," is the first publication to identify a modulator of the function of these key potassium channels. Prior to this discovery, the activity of the isolated channel was found to be significantly different from the natural activity measured in the brain. The companies believe that these KChIPs are important missing components of native A-type potassium channels which helps explain the difference. The identification of these additional components may allow for the development of new drug screens to identify compounds that modulate A-type potassium channels in a tissue-specific manner. This may allow for the development of therapeutics for CNS disorders that do not cause unwanted side effects in other non-brain tissues such as the heart.

"We have found that KChIPs restore many important features of the physiological properties of native A-type potassium channels," said Frank An, Ph.D., scientist at Millennium and first author on the paper. "KChIPs may modulate specific potassium currents and therefore also regulate the excitability of key neurons in the brain. This discovery may prove important to understanding the molecular basis of a wide range of central nervous system diseases."

"The discovery and publication of key potassium ion channel modulating proteins is a good example of the collaborative scientific effort between Millennium and Wyeth-Ayerst scientists," said Ken Rhodes, Ph.D., a scientist at Wyeth-Ayerst and one of the authors of the Nature paper.

In 1998, Millennium and Wyeth-Ayerst announced the discovery of a novel gene that regulates the activity of this ion channel, and encodes one of these KChIPs, which triggered a milestone payment to Millennium. This potassium channel has been implicated in several disorders and diseases including anxiety, depression, ischemia and epilepsy. Ion channels in general are involved in all physiological functions within the body, and therefore, have attracted broad interest as targets for therapeutics.

This joint research was conducted under Millennium's collaboration with Wyeth-Ayerst to develop novel treatments for a broad range of CNS diseases. The companies' original agreement, which began in 1996, was extended for an additional two years in 1999. A separate alliance between Millennium and Wyeth-Ayerst, formed in December 1996, focuses on antibacterial drug discovery. Millennium has delivered nine antibacterial drug targets to Wyeth-Ayerst since that alliance began.

Wyeth-Ayerst Research is a major research-oriented pharmaceutical company with leading products in the areas of women's healthcare, cardiovascular and metabolic disease therapies, central nervous system drugs, anti-inflammatory agents, vaccines and genetic pharmaceuticals. American Home Products Corporation is a world leader in the research, development and marketing of pharmaceuticals and other health-care products. It is also a leader in agricultural products, animal health care, medical devices and food products.

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. The Company is applying this platform to integrate the initial discovery of disease-related genes, the development of drugs specific for these diseases and the management of patients affected by these diseases. Headquartered in Cambridge, Massachusetts, Millennium and its affiliates currently employ more than 1,000 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 unanticipated difficulties and delays relating to gene identification, drug discovery and clinical development processes; Millennium's ability to successfully integrate the operations of LeukoSite, Inc.; 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 substantial additional funds required for progress in drug discovery and development. The factors that could affect the performance of Millennium 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 "Risk Factors" in the registration statement on Form S-4 filed by Millennium with the Securities and Exchange Commission on November 5, 1999.

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