On August 1, 2001, AVANT announced it has suspended enrollment in its two Phase IIb studies of TP10 in infants undergoing cardiac surgery following receipt from the Data Safety Monitoring Board (DSMB) of a request for additional detailed information from these studies, including patient records for reported serious adverse events.  The DSMB has met and reviewed the information requested, and has indicated that patient enrollment may be reinstated, with the recommendation to add additional laboratory tests to the study protocol.  The U.S. Food and Drug Administration (FDA) has been notified that patient enrollment in the studies has temporarily been suspended.  In response, the FDA has placed the pediatric programs on clinical hold, pending their review of these additional data.  While we have not received written notification of the FDA’s specific questions and requests, we are working closely with the Agency to resolve this matter expeditiously.  AVANT believes that this is a short-term situation and we are committed to complying with the FDA’s formal requests as soon as they are received.  The Agency’s review of the pediatric TP10 studies does not affect the adult cardiac surgery program, which is continuing as planned.

             AVANT is actively enrolling a placebo-controlled Phase II trial in approximately 600 adult patients undergoing cardiac surgery utilizing cardiopulmonary bypass.  This 30-center study is a dose-ranging study that will allow us to further define our clinical endpoints in the adult patient population before moving ahead to a number of pivotal clinical trials.  This adult study is intended to investigate the efficacy and safety of TP10 in a population known to be at high risk of medically important adverse outcomes that have a real effect on the long-term health of a substantial population.  AVANT may partner the adult program when additional clinical data becomes available.

             Cholesterol Treatment Vaccine:  We are developing a therapeutic vaccine against endogenous cholesteryl ester transfer protein (CETP), which may be useful in reducing risks associated with atherosclerosis.  CETP is a key intermediary in the balance of HDL and LDL.  We are developing a vaccine (CETi-1) to stimulate an immune response against CETP, which we believe may improve the ratio of HDL to LDL cholesterol and reduce the progression of atherosclerosis.  We have conducted preliminary studies in rabbits, which have demonstrated the ability of CETi-1 vaccine to elevate HDL and reduce the development of blood vessel lesions.

             In 1999, we initiated a double-blind placebo controlled, Phase I clinical trial of our CETi-1 vaccine in adult volunteers.  The object of the study was to demonstrate the safety of single administrations of the vaccine at four different dosage strengths.  The vaccine was very well tolerated in the 48 adult volunteers who participated in the study.  The only serious adverse reaction reported during the study (allergic reaction to shower gel) was not related to study medication.  There were no differences in the safety profiles of placebo groups and active vaccine groups.  In addition, there was limited evidence of an immune response in one subject treated with the highest dose.

             In February 2001, AVANT announced preliminary results from a double-blinded placebo controlled extension of the earlier completed Phase I trial of our CETi-1 vaccine in healthy adult volunteers.  Results from the extension study showed measurable antibody titers in all dose groups treated with study medication, suggesting a dose-response relationship.  These data have been extremely helpful in designing a Phase II study of patients with low levels of HDL, which we plan to begin later this summer.  As clinical data becomes available, we plan to seek a corporate partner to complete development and to commercialize the vaccine.

             Cholera Vaccine:  We are developing a single dose, oral cholera vaccine using a live, genetically attenuated cholera strain.  Based on this technology, discovered in academia, we have developed the vaccine through early Phase II trials.  We then negotiated a collaboration agreement under which a Phase IIb trial was performed and funded by the Walter Reed Army Institute of Research (WRAIR) and the National Institute of Health (NIH).  This trial, initiated in October 2000, was designed to test the safety, immunogenecity and protective capacity of AVANT’s single dose, oral cholera vaccine, Peru-15, against a challenge with live virulent cholera.  In May 2001, we announced results from this Phase IIb human challenge study.  Peru-15 showed 100% protection against moderate and severe diarrhea and 93% protection against any diarrhea.  The study results suggest that, if confirmed by further investigation, Peru-15 may be an excellent candidate as a potential single dose, oral vaccine for travelers going to areas where cholera is endemic.