Berkeley HeartLab, Inc. Gains Exclusive License to New Heart Disease Diagnostic Test Panel from Ernest Orlando Lawrence Berkeley National Laboratory; New Diagnostic Test Panel Identifies Key Risk Factors Cited by American College of Cardiology.

SAN MATEO, Calif.--(BUSINESS WIRE)--May 13, 1996--Berkeley HeartLab, Inc., a company focusing on new diagnostic technology for detecting heart disease, announced today it has signed a $3.8 million, five-year research agreement with a technology option with Ernest Orlando Lawrence Berkeley National Laboratory (LBNL) to acquire exclusive worldwide rights to a new diagnostic technology that is a major improvement over existing cholesterol tests in measuring heart disease risk factors.

Cardiovascular disease is the nation's leading cause of death in the U.S., accounting for 35 to 40 percent of all deaths.

The proprietary screening technology is the foundation for a new diagnostic test panel being developed by the newly formed Berkeley HeartLab, a privately-held company that will commercialize the test panel, making it widely available to the public for the first time. The new technology is seen as the next generation in heart disease screening because it can identify the large number of heart disease candidates who have the same cholesterol profile as those who do not develop heart disease. Early screening for heart disease risk will assist physicians in better selecting appropriate therapy. In many cases, customized therapy will halt progression of coronary artery disease and therefore reduce the need for expensive surgery.

Measures Risk Factors Cited by ACC 

Berkeley HeartLab also said the new heart disease test panel measures several newly discovered risk factors and abnormalities, including the size of low-density lipoprotein particles (LDL) -- often referred to as "bad cholesterol." The new abnormalities are among the major identifiable and manageable heart disease risk factors cited by the American College of Cardiology in a task force statement published in the association's April 1996 issue of the Journal of the American College of Cardiology. As a result, Berkeley HeartLab expects that cardiologists will begin to use the new test panel as a "first-line" screening for heart disease patients and family members.

Next Generation of Cholesterol Testing

Cardiovascular disease ranks as the leading cause of mortality and morbidity in the United States, causing 954,000 deaths in 1993, according to the American Heart Association. Of this total, more than 489,000 deaths were due to coronary artery disease in the United States. Current testing methods used to determine an individual's risk of developing heart disease are generally confined to measuring total cholesterol, LDL, high-density lipoproteins (HDL or "good cholesterol") and triglycerides. Risk factors identified by these measurements include elevated cholesterol and elevated triglycerides, elevated LDL levels and low HDL levels. But these tests do not identify a substantial portion of patients who eventually develop heart disease.

Measuring New High-Risk Factors

A research team led by Ronald Krauss, M.D., director of the Department of Molecular and Nuclear Medicine at LBNL and H. Robert Superko, M.D., director of the Cholesterol, Genetics and Heart Disease Institute has developed a 10-test investigative panel which includes current parameters of cardiovascular risk -- total cholesterol, LDL, HDL and triglycerides -- plus six new tests designed to identify high-risk factors.

The 10-test panel has been used by LBNL researchers to investigate thousands of patients since 1990, as part of the lab's clinical research program. The licensing of the technology will allow the test to be made widely available commercially. Berkeley HeartLab said it plans to seek 510K approval for the investigative panel from the U.S. Food and Drug Administration (F.D.A.)

In addition to measuring current cardiovascular risk factors, the new diagnostic technology provide six other risk factor tests, including LDL particle size:

LDL Particle Size -- Low Density Lipoprotein, or LDL, particles contribute to heart disease risk and high LDL-cholesterol is well established as a heart disease risk factor. However, most people with heart disease do NOT have classic elevated LDL cholesterol. LDL particles can be present in a variety of sizes and the small LDL's (known as LDL pattern B) create substantially higher heart disease risk compared to large LDL's (known as LDL pattern A) even when LDL cholesterol is "normal."

Measurement of LDL cholesterol does not determine these two categories of LDL. The small LDL characteristic is determined, in any given individual, by inherited traits. Approximately 50 percent of men with heart disease express the small LDL trait and approximately 50 percent of their first degree relatives can express it as well. The presence of small LDL increases the risk of heart disease by 300 percent.

Patients with LDL pattern B can be successfully treated, often with a combination of diet, weight control, and lipid lowering medications. Diet and drug therapy recommendations are different for LDL pattern A individuals. Patients with LDL pattern B can respond quite well to specialized lipid lowering therapy and achieve heart disease stability, and some degree of regression.

HDL Subclassification -- HDL participated in "reverse cholesterol transport." An abundance of HDL2b reflects good "reverse cholesterol transport," while a deficiency of HDL2b reflects poor "reverse cholesterol transport." HDL cholesterol does not reflect the proportion of the different types of HDL's. Low HDL2b can be improved by specific therapy.

Lp(a) - Lp(a) is an LDL particle with the protein (a) attached. This inherited trait is present in approximately 33 percent of heart disease patients and in 50 percent of their first degree relatives. It increases the risk of heart disease 300 percent and is not detected on routine blood tests. It is a powerful predictor of heart attacks in "young" men, and of vein graft blockage following bypass surgery. The presence of Lp(a) greatly increases the danger of other risk factors.

Apoprotein B - Apoprotein B is a single protein attached to the LDL particle. This test gives a more accurate measurement of the relative number of LDL particles than the current standard cholesterol blood test. Elevated apoprotein B identifies a high risk state even in the presence of "normal" LDL cholesterol. Elevated apoprotein B can be reduced with therapy.

Apoprotein AI - Apoprotein AI is one of several proteins attached to the HDL particle. It may be a better predictor of heart disease risk than HDL cholesterol. Low level of apoprotein AI can be increased with several therapies.

Apoprotein E Isoforms - Apoprotein E is attached to several lipoprotein classes and differences (isoforms) exist in "normal" and "abnormal" forms which are inherited. The presence of abnormal forms can predispose individuals to heart disease and blood lipid abnormalities. The presence, or absence, of different isoforms affects the potential success of diet and drug therapy.

The addition of these new tests provides physicians with more relevant diagnostic information for identifying heart disease candidates and assessing subsequent treatment. Early screening for and management of heart disease will allow physicians to more accurately design a customized treatment approach, reducing the need for expensive hospitalization or surgical intervention.

"The commercialization of this technology allows us to bring immediate benefits to millions of Americans who now suffer from cardiovascular disease," said Robert L. Swift, Ph.D., president and chief executive officer of Berkeley HeartLab. "More importantly, we will be able to identify the millions of Americans who have an inherited cardiovascular risk factors, so that the disease does not progress to a stage requiring costly surgical treatment."

Swift said Berkeley HeartLab will operate a centralized diagnostic service laboratory in Berkeley, Calif., that will analyze patient blood samples provided by cardiologists and a range of other physicians. The laboratory is certified under the F.D.A.'s CLIA (Clinical Laboratory Improvement Amendments) regulations. The commercial testing service is expected to begin operation in May 1996.

Researchers at the LBNL, who first isolated lipoproteins in 1949, have been world leaders in studying the connections between cholesterol and heart disease for more than 40 years. The LBNL was also the first to identify subclasses of lipoproteins and to determine that the ratio of high density-to-low density lipoproteins is a strong indicator of heart disease. The development of the testing technology and the licensing of it to the private sector is part of the laboratory's charter to convert its research breakthroughs into viable technologies for civilian applications.

First Product from New Company

The technology licensed from LBNL is the basis of the first product to be marketed by the newly formed Berkeley HeartLab, Inc., a privately-held company founded in March 1996. The company has raised an initial round of financing through individual investors. Berkeley HeartLab is headed by a management team that includes co-founder Robert L. Swift, Ph.D., president and chief executive officer, co-founder Dennis J. Sheehan, M.D., a member of the board of directors, and David L. Kaufman, M.D., vice president, technical operations. H. Robert Superko, an internationally known lipid specialist and director of the Cholesterol, Genetics and Heart Disease Institute, serves as medical advisor to the company.

Robert L. Swift, Ph.D., co-founder, president, chief executive officer and director, was a co-founder and former vice president of operations and development of COR Therapeutics. Prior to joining COR, Dr. Swift was director, clinical research at Genentech and director, product planning and development at Pfizer Pharmaceutics.

Dennis J. Sheehan, M.D., co-founder and a member of the board of directors, is a fellow of the American College of Cardiology and the American Society of Angiography. He is a cardiology consultant at Sequoia Hospital, Redwood City, CA, and a clinical assistant professor of medicine at Stanford University Medical Center.

David L. Kaufman, M.D., M.P.H., vice president, technical operations, was previously vice president - clinical affairs and medical director, Circadian, Inc., where he developed and managed disease management programs and participated in development and manufacture of diagnostic and electrosurgical devices.

CONTACT: Berkeley HeartLab, Inc.

Robert Swift, 415/378-8513

or

StratiPoint Group, Inc.

Mike Jackman or Carole Melis, 415/326-0420