Millinium discovers ACE2, a novel cardiovascular drug target, with potential to lead to new treatments

August 30, 2000

Discovery Published in the Journal Circulation Research

CAMBRIDGE, Mass., August 31, 2000 -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM) today announced it has discovered a potential new target for treating cardiovascular disease. The discovery of ACE-related carboxypeptidase (ACE2), the first known human homologue of angiotensin-converting enzyme (ACE), is described in the August 31st issue of Circulation Research, a publication of the American Heart Association. Together, Millennium and Eli Lilly and Company (NYSE: LLY), Millennium's partner in heart failure research, will pursue the development of potential drugs targeted to ACE2 for the treatment of congestive heart failure.

The findings, reported in the article, "A Novel Angiotensin-Converting Enzyme-Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1-9," were made by a team of Millennium scientists lead by Susan Acton, Ph.D. ACE2 is significant because it is the first identified human homologue of ACE, a known catalyst in hypertension and congestive heart failure, and is therefore, a potential new target for these cardiovascular diseases.

The data indicate significant differences between the ACE2 and ACE genes. ACE, which is found throughout the vascular system, produces a potent vasoconstrictor, angiotensin II. ACE inhibitor drugs, a class of therapy currently on the market, reduce both hypertension and morbidity and mortality from heart failure by blocking the production of angiotensin II. In contrast to ACE, ACE2 is specifically expressed in the heart, kidneys, and testes and produces an angiotensin peptide whose function is currently unknown. In addition, ACE2 is not inhibited by current ACE inhibitor drugs on the market.

"Because ACE2 is restricted to the heart and kidneys, it holds promise for the development of very specific drugs for the treatment of cardiovascular disease," said Roger Breitbart, M.D., senior director of cardiovascular biology at Millennium. "Millennium and Lilly scientists are moving this novel target into preclinical validation studies with the goal of developing innovative treatments for congestive heart failure, an area of tremendous unmet medical need.

"This novel and very exciting target signifies the strength of Millennium's scientific effort in the discovery and development of potential breakthrough therapeutic and predictive medicine products, said Robert Tepper, M.D., chief scientific officer at Millennium. "Further, this target validates Millennium's genomics-based approach to drug discovery and development, and is exemplary of the hundreds of other discoveries Millennium is pursuing within our broad research pipeline."

Millennium scientists discovered ACE2 as part of ongoing search for novel genes related to heart failure. It was identified from thousands of gene sequences obtained from biopsies of human heart tissues. Millennium uses a unique genomics-based approach to drug discovery, employing the Company's leading, integrated technology platform. This gene-to-patient platform employs DNA arrays, computational biology, and cell-based and genetic disease models, as well as an integrated chemical lead discovery and validation platform. Scientists use this platform to discover genes in novel molecular pathways that lead to diseases, such as congestive heart failure, and then to validate the potential of these genes as innovative therapeutic targets for breakthrough medical products.
Further Research in Cardiovascular Disease
Millennium and Lilly scientists will be presenting additional scientific research in the area of congestive heart failure at two national scientific meetings this fall.

Background on Cardiovascular Disease and Congestive Heart Failure
According to the American Heart Association, almost 60 million Americans suffer from one or more types of cardiovascular diseases (CVD). In 1997, CVD caused 953,110 deaths (41.2 percent of all deaths); about one sixth of all people killed by CVD are under age 65. There are three major risk factors for CVD, including cigarette smoking, high blood cholesterol and hypertension, all of which are modifiable with treatment.

Congestive heart failure is a condition in which the heart cannot pump enough blood to meet the needs of the body's other organs. Approximately 4,600,000 Americans suffer from congestive heart failure (CHF), with 550,000 new cases occurring each year. Seventy-five percent of patients have hypertension prior to the development of CHF. The five-year mortality rate for CHF is about 50 percent.

Millennium, a leading biopharmaceutical company, applies its comprehensive and integrated science and technology platform for the discovery and development of breakthrough therapeutic and predictive medicine products, with a goal of delivering personalized medicine. Through the industrialization of this gene-to-patient platform, Millennium is also striving to accelerate the process of drug discovery and development. Headquartered in Cambridge, Massachusetts, Millennium and its affiliates currently employ more than 1,000 people.

This press release contains "forward-looking statements." These statements include descriptions of Millennium's operational plans, expectations about future earnings and other results of operations, views of future industry or market conditions, and other statement that include words like "may," "expects", "believes," and "intends," and that describe opinions about future events. Known and unknown risks may cause Millennium's actual results and performances to be materially different from those expressed or implied by these statements. Some of these risks are: uncertainties relating to unanticipated difficulties and delays 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 substantial additional funds required for progress in drug discovery and development. These and other factors are identified and more fully explained in Exhibit 99.1 (entitled "Risk Factors") to the quarterly report on Form 10-Q filed by Millennium with the Securities and Exchange Commission on July 26, 2000.

Lilian Stern (investor)
Sally McCraven (media)
Millennium Pharmaceuticals, Inc.

Porter Novelli

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