NeXstar Pharmaceuticals files IND for MiKasome.

BOULDER, Colo.--(BUSINESS WIRE)--Oct. 2, 1996--NeXstar Pharmaceuticals, Inc. (NASDAQ:NXTR) announced today that it has filed an Investigational New Drug application (IND) with the U.S. Food and Drug Administration (FDA) for clinical testing of MiKasome in patients with a variety of serious bacterial and mycobacterial infections.

MiKasome is a proprietary liposomal antibiotic designed to improve the efficacy and decrease the toxicity associated with a family of antibiotics known as aminoglycosides.

Amikacin, the active ingredient in MiKasome, is a member of the aminoglycoside family.

The initial U.S. clinical trial for MiKasome will involve up to 30 asymptomatic HIV-infected men and women over 18 years of age. This phase I clinical study is designed to evaluate MiKasome's safety and to determine the appropriate therapeutic dose range for subsequent efficacy studies.

The Company has already conducted a smaller Phase I safety study in Europe. No serious adverse events were observed, and measurements of kidney and auditory function did not change at any of the 5 doses administered in the trial.

"With this filing, MiKasome becomes the third liposomal drug that NeXstar Pharmaceuticals has brought into the clinic in the U.S.," said Patrick J. Mahaffy, President and Chief Executive Officer. "We look forward to the results of the upcoming Phase I trial to guide us in developing future trials for this drug."

Raymond A. Bendele, DVM, Ph.D., NeXstar Pharmaceuticals' Senior Director for Life Sciences, added, "Our preclinical studies have shown that MiKasome is more than just an improved form of amikacin. For example, our toxicology studies showed that blood levels of MiKasome can exceed by 50-fold the maximum tolerated levels of free amikacin. Data such as these lead us to believe that we have created a broad-spectrum antibiotic with a superior safety and efficacy profile compared to that of conventional aminoglycosides. We hope to demonstrate this superiority in our clinical trials program."

Preclinical studies also suggest that MiKasome, compared to other aminoglycosides, distributes through the body differently, which may reduce significantly the kidney damage or hearing loss often associated with aminoglycoside therapy. Aminoglycosides are used primarily to treat infections caused by oxygen-requiring gram- negative bacteria despite the fact that all aminoglycosides are toxic to varying degree to the kidney and to sensory cells in the inner ear.

Certain of the illnesses that MiKasome may be able to treat include those caused by mycobacterial infections. These include tuberculosis (TB) and mycobacterium avium complex (MAC), a disease that affects primarily AIDS patients during the late stages of the disease. Other illnesses that may be susceptible to MiKasome therapy include hospital-based pneumonia, gram negative bacterial infections, acute infections that patients with cystic fibrosis or chronic obstructive pulmonary disease, and endocarditis, a serious heart infection, most often involving the heart valves, that occurs in patients with blood-borne bacterial infections. The Company is continuing a substantial preclinical program to support clinical trials in these and other indications.

NeXstar Pharmaceuticals, Inc. is an integrated pharmaceutical company engaged in the discovery, development, manufacturing and marketing of products to treat life-threatening diseases. The Company currently markets two drugs, AmBisome and DaunoXome. The Company has headquarters in Boulder, Colorado; research, development and manufacturing facilities in San Dimas, California; Antwerp, Belgium; Lakewood, Colorado, and Boulder; and marketing subsidiaries worldwide.

Fact Sheet NeXstar Pharmaceuticals MiKasome

What is MiKasome?

MiKasome is a liposomal formulation of amikacin, a potent yet toxic antibiotic used to treat a variety of bacterial and mycobacterial infections. Liposomes are microscopic fat bubbles that can be used to encapsulate drugs, in essence creating a new drug that has different safety and efficacy characteristics than the free drug.

What are amikacin and aminoglycoside antibiotics?

Amikacin is a member of the aminoglycoside family of antibiotics, which also includes gentamicin, tobramycin, vancomycin and kanamycin. Aminoglycosides kill bacteria by inhibiting protein synthesis, an activity necessary for life. Aminoglycosides are particularly effective against gram-negative bacteria, a large group of organisms resistant to most other types of antibiotics, although amikacin is also active against certain important gram-positive bacteria that are resistant to other antibiotics. Amikacin's unusual chemical structure, compared to that of the other aminoglycosides, makes it difficult for even gram-negative bacteria to develop resistance to this antibiotic as they can with other aminoglycosides.

Amikacin, like other aminoglycoside antibiotics, is toxic to the kidneys. Kidney toxicity occurs because more than 90 percent of the drug is removed from the blood stream through the kidneys within 24 hours of administration. MiKasome's lowered toxicity to the kidneys in animal studies probably results from the far slower clearance through the kidneys.

What illnesses might be treated with MiKasome?

Tuberculosis (TB): TB is the leading cause of illness and death from infection worldwide. According to the World Health Organization, nearly 9 million people developed TV and some 3 million died from the disease in 1995. Over 160,000 new cases of TB were reported last year in industrialized countries, with some 24,000 new cases reported in the U.S. alone. Drug resistance is a growing problem in the treatment of TB, and amikacin therapy is now recommended for those patients with antibiotic-resistant TB.

Mycobacterium avium complex (MAC): MAC, which affects 33,000 people yearly in the U.S., Canada and Europe, is a complex of illnesses caused by 28 different subtypes of mycobacteria, the majority of which are resistant to most antibiotics. However, a recent survey found that 23 percent of the MAC subtypes were susceptible to amikacin therapy. Preclinical studies have shown that MiKasome was significantly better at killing MAC in the liver, spleen and kidney than was free amikacin.

Acute infections in cystic fibrosis (CF) patients: Cystic fibrosis is the most common fatal genetic disease among the Caucasian population, affecting some 25,000 people in the U.S. and 60,000 people total worldwide. In cystic fibrosis, the mucus secreted by the lung lining becomes thickened and difficult to clear. This mucus provides an ideal environment for bacterial infection, and repeated cycles of infection and inflammation result in lung damage that ultimately leads to death. Most CF patients are colonized by one or more types of bacteria early in life, and aminoglycosides are a standard part of the antibiotic therapy used to treat the acute infectious episodes, or exacerbations, that regularly afflict CF patients.

Acute infections in chronic obstructive pulmonary disease (COPD): Individuals with COPD are susceptible to repeated infections by gram-negative bacteria susceptible to aminoglycoside therapy. These infections result in some 200,000 hospital admissions annually in the U.S. alone, and more than 400,000 admissions in Europe and Japan.

Pneumonia: Gram-negative bacteria are a major cause of pneumonia that affects hospitalized patients, and aminoglycosides are an important part of the standard treatment for hospital-based pneumonia. In the U.S., over 165,000 cases of gram-negative pneumonia are treated yearly. Worldwide, the incidence of this life-threatening condition approaches 500,000 cases annually.

General gram-negative bacterial infections: Only a few decades ago, gram-negative bacterial infections were relatively rare. Today, they are the most common cause of death in intensive care units, and their management is one of the more complex and serious problems facing critical care physicians. More than half of the deaths caused by gram-negative bacterial infections occur within the first two days, making early administration of broad-spectrum antibiotic therapy, including aminoglycosides, critical to effective treatment. Worldwide, approximately 1.4 million people develop hospital-based gram-negative bacterial infections each year, with nearly 500,000 cases reported annually in the U.S.

Endocarditis: Infective endocarditis is a microbial infection of a cardiac valve or lining of the heart (endocardium) that affects approximately 15,000 people annually worldwide. Aminoglycosides are used together with other antibiotics to treat endocarditis.

CONTACT: NeXstar Pharmaceuticals Inc., Boulder

Joseph Alper, 303/546-7717

Katy Doherty, 303/546-7889

web site at http://www.nexstar.com