Results of a Phase I and Extension Study of AVANT Immunotherapeutics' Novel Cholesterol Management Vaccine Published in Atherosclerosis.

Business Editors/Health/Medical Writers

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NEEDHAM, Mass.--(BUSINESS WIRE)--July 17, 2003

Research published today in the journal Atherosclerosis supports the feasibility, immunogenicity and safety of an experimental vaccine approach to raising HDL cholesterol under development by AVANT Immunotherapeutics (Nasdaq: AVAN). The publication details results of a dose-ranging, placebo-controlled Phase I human trial and extension study of AVANT's cholesterol ester transfer protein (CETP) vaccine, CETi-1. This investigational vaccine is designed to elicit antibodies that bind and inhibit the activity of CETP, blocking the ability of that protein to transfer cholesterol from HDL to LDL and thus causing HDL cholesterol levels to rise. A Phase II trial of the CETi-1vaccine, evaluating the effect of that experimental treatment on HDL levels in patients with low initial HDL cholesterol, is nearing completion, with results expected in the fourth quarter of this year.

"Results of this Phase I trial showed that a single administration of the CETi-1 vaccine was well tolerated at each of four doses studied, as well as in a subset of patients who received a further booster dose," said Michael H. Davidson, M.D., Director of Preventive Cardiology at Rush Presbyterian-St. Luke's Medical Center and principal investigator for the study conducted at the Chicago Center for Clinical Research. "We would not expect to see measurable antibody responses following a single administration of vaccine, but more than half of the patients receiving a second vaccine injection (8/15) developed a dose-related immune response. Importantly, 100% (4/4) of the patients treated with the highest dose showed a long lasting antibody response. This clearly demonstrates the ability of the vaccine to elicit specific anti-CETP antibody formation. The vaccine was well tolerated at all doses with incidence of adverse events being similar in the placebo and CETi-1 groups. The most commonly reported adverse events were headache, rhinitis and sinusitis." He noted that the booster injection was administered using a sub-optimal dosing interval in order to ensure the collection of adequate safety data following the initial vaccine administration. Thus, the investigators did not expect that subjects in this Phase I trial would show any reduction in CETP function or change in lipid profiles.

"Preclinical studies of the CETi-1 vaccine in the standard animal model used to evaluate cholesterol-moderating therapies resulted in a 35% increase in plasma HDL and a 39.6% reduction in aortic lesions in vaccinated animals compared to controls," said study co-author, Alistair Wheeler, M.D., Vice President of Medical Affairs at AVANT. Additionally, Dr. Wheeler noted that patients with low HDL participating in the currently ongoing Phase II study of CETi-1 were receiving a series of four vaccine injections at time intervals more likely to produce a profound immune response in comparison to the vaccine injection intervals used in the Phase I trial.

"Clinical research with CETi-1 continues to support its development as a novel approach to cholesterol management designed to raise heart-protective HDL cholesterol - a need not well addressed by current cholesterol management therapies," said Una Ryan, Ph.D., President and Chief Executive Officer of AVANT Immunotherapeutics. She commented that recent clinical research by others with small molecule inhibitors of CETP had shown reductions in CETP activity as well as increases in HDL cholesterol at the highest studied doses, and said that a successful vaccine could offer significant benefits compared to daily drug therapies.

"A major limitation today to the successful management of patients with lipid disorders is their lack of long-term compliance with oral therapies," said Dr. Ryan. "A vaccine approach involving an annual or bi-annual treatment could overcome compliance issues, leading to better clinical outcomes and potentially lower cost of therapy."

AVANT Immunotherapeutics is engaged in the discovery, development and commercialization of products that harness the human immune system to prevent and treat disease. The company is developing a broad portfolio of vaccines addressing a wide range of applications including bacterial and viral diseases, chronic human disease, biodefense and food safety. These include single-dose, oral vaccines that protect against important disease-causing agents and a novel, proprietary vaccine candidate for cholesterol management. AVANT's goal is to demonstrate proof-of-concept for its products before leveraging their value through partnerships. Current collaborations encompass the development of an oral human rotavirus vaccine, vaccines to combat threats of biological warfare and vaccines addressed to human food safety and animal health.

Additional information on AVANT Immunotherapeutics, Inc. can be obtained through our site on the World Wide Web: http://www.avantimmune.com.

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. These forward-looking statements are based on management's beliefs and assumptions and information currently available. The words "believe", "expect", "anticipate", "intend", "estimate", "project" and similar expressions which do not relate solely to historical matters identify forward-looking statements. Investors should be cautious in relying 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 integration of the UPT technology and programs; (2) the ability to adapt AVANT's vectoring systems to develop new, safe and effective orally administered vaccines against anthrax and plague or any other microbes used as bioweapons; (3) the ability to successfully complete development and commercialization of CETi-1 and of other products; (4) the cost, timing, scope and results of ongoing safety and efficacy trials of CETi-1 and other preclinical and clinical testing; (5) the ability to successfully complete product research and further development, including animal, pre-clinical and clinical studies of CETi-1 and other products; (6) the ability of the Company to manage multiple late stage clinical trials for a variety of product candidates; (7) the volume and profitability of product sales of Megan(R)Vac 1 and other future products; (8) changes in existing and potential relationships with corporate collaborators; (9) the cost, delivery and quality of clinical and commercial grade materials supplied by contract manufacturers (10) the timing, cost and uncertainty of obtaining regulatory approvals to use CETi-1, among other purposes, to raise serum HDL cholesterol levels and for other products; (11) the ability to obtain substantial additional funding; (12) the ability to develop and commercialize products before competitors; (13) the ability to retain certain members of management; and (14) other factors detailed from time to time in filings with the Securities and Exchange Commission. We expressly disclaim any responsibility to update forward-looking statements.