New research illustrates role of CETP in atherosclerosis

November 28, 1999

Supports concept of avant immunotherapeutics' atherosclerosis vaccine

NEEDHAM, MA (November 29, 1999): New research demonstrates that the cholesteryl ester transfer protein (CETP) can promote atherosclerosis, thus supporting the novel vaccine approach to preventing or treating that disease now under development by AVANT Immunotherapeutics, Inc. (Nasdaq: AVAN). A study published in the December issue of Nature Medicine by researchers from Boston University School of Medicine and AVANT describes the creation of a transgenic rat model that carries the human gene for CETP in a rat strain that develops high blood pressure. As they aged, such rats developed severely high cholesterol and triglyceride levels, atherosclerotic lesions, myocardial infarctions (heart attacks), and had decreased survival, thus closely mimicking human atherosclerosis and coronary heart disease.

"This research strongly suggests that elevated CETP may contribute to the development of atherosclerosis in humans. It also substantiates a mechanism for the known epidemiological link between increased risk of coronary heart disease and increasing severity of hypertension," said Victoria L. M. Herrera of Boston University School of Medicine, lead author of the publication. "We believe this transgenic rat line will prove a useful predictive model for research in cardiovascular disease."

The normal role of CETP in the body is to shuttle cholesterol from high density lipoprotein (HDL, or "good" cholesterol) to low density lipoprotein (LDL, or "bad" cholesterol), thus controlling in part the relative levels of those two substances. High levels of LDL and low levels of HDL are known to contribute to atherosclerosis. AVANT's investigational vaccine is designed to raise serum HDL cholesterol levels by inducing antibodies against a critical portion of the CETP molecule, thus blocking its cholesterol shuttling activity and inducing a plasma lipoprotein profile consistent with a lower risk of atherosclerosis (high HDL and low LDL).

"AVANT has long believed that CETP contributes to the development of atherosclerosis in humans. This latest research strengthens the story about the role this molecule plays in the development of the disease and confirms that our vaccine, which may prevent or treat atherosclerosis, is aimed at the right target," said Una Ryan, Ph.D., president and chief executive officer of AVANT Immunotherapeutics.

In preliminary studies of AVANT's CETP vaccine, treated rabbits exhibited an increase in the level of HDL and significantly fewer atherosclerotic lesions in their blood vessels compared to untreated rabbits, which showed no increase in HDL levels and developed significant blood vessel lesions. In June of 1999, AVANT announced it received approval to begin enrollment in its double-blind, ascending-dose Phase I clinical trial of this investigational vaccine, called CETi-1. That study is now ongoing at the Chicago Center for Clinical Research (CCCR).

Atherosclerosis, which can manifest itself as a heart attack, stroke or peripheral vascular disease, is one of the leading causes of morbidity and mortality in the United States and most of the Western World.

The study described in this article published in Nature Medicine was supported in part by an SBIR Grant from the National Heart, Lung and Blood Institute, National Institutes of Health.

AVANT Immunotherapeutics, Inc., is engaged in the discovery, development and commercialization of products that harness the human immune response to prevent and treat disease. The Company's lead therapeutic program is focused on compounds that inhibit the inappropriate activity of the complement cascade, which is a vital part of the body's immune defense system. The Company is also engaged in the development of Therapore', a novel system for the delivery of immunotherapeutics for chronic viral infections and certain cancers. The Company and its collaborators are developing vaccines using its proprietary adjuvants, Adjumer' and Micromer'. In a further collaboration, the Company is developing an oral human rotavirus vaccine, and is developing its own proprietary vaccine for the management of atherosclerosis.


Additional information on AVANT Immunotherapeutics, Inc., can be obtained through the Company's site on the World Wide Web:

Safe Harbor Statement Under the Private Securities Litigation Reform Act of 1995: This release includes forward-looking statements which reflect AVANT's current views with respect to future events and financial performance. The words "believe," "expect," "anticipate," and similar expressions identify forward-looking statements. Investors should not rely on forward-looking statements because they are subject to a variety of risks, uncertainties, and other factors that could cause actual results to differ materially from those expressed in any such forward-looking statements. These factors include, but are not limited to: (1) the ability to successfully complete development and commercialization of products, including the cost, scope and results of preclinical and clinical testing; (2) the ability to successfully complete product research and further development, including animal, pre-clinical and clinical studies; (3) changes in existing and potential relationships with! ! corporate collaborators; (4) the time, cost and uncertainty of obtaining regulatory approvals; (5) the ability to obtain substantial additional funding; (6) the ability to develop and commercialize products before competitors; and (7) other factors detailed from time to time in filings with the Securities and Exchange Commission.

AVANT Contacts:

Una S. Ryan, Ph.D.
President and CEO
AVANT Immunotherapeutics, Inc.

AVANT Media Contact:

Joan Kureczka
J. Kureczka Associates

Boston University Media Contact:

Gina Di Gravio
B.U. School of Medicine

Kureczka/Martin Associates

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