Monday, Sep 23, 1991

Incyte And Genentech To Develop Drug For Treating Septic Shock

SOUTH SAN FRANCISCO, Calif. -- Sept. 23, 1991 -- Genentech, Inc.(NYSE: GNE) and Incyte Pharmaceuticals Inc. have signed a $14 million agreement to develop and commercialize a human protein called BPI. This naturally-occurring molecule offers potential as a treatment for gram-negative septic shock and related conditions which cause fatalities of 70,000-100,000 hospitalized and immuno-compromised Americans yearly.

Under the terms of the agreement, Incyte will receive research and development support for an initial three-year period, as well as milestone-based payments and royalties on product sales. Genentech also will acquire an equity position in Incyte. In addition, Genentech will have exclusive rights to market BPI worldwide, except in Japan and the Far East, where Incyte retains all rights.

Explaining why Genentech has chosen to collaborate with Incyte on the development of BPI, G. Kirk Raab, Genentech's president and chief executive officer, said: "Genentech is seeking out research alliances which complement our own substantial efforts. Through this and similar agreements with other biotechnology companies, we can focus our own research and development efforts on priority projects in-house, while still benefiting from emerging technologies that fit in with our overall product development plan."

Both Genentech and Incyte Pharmaceuticals have been exploring the value of BPI (Bactericidal/Permeability Increasing Protein) for several years. Genentech researchers cloned the DNA of BPI in collaboration with scientists at New York University. Incyte researchers discovered that the molecule is the body's natural inactivator of endotoxin released by gram-negative bacteria. Endotoxin is a toxic substance that can provoke a chain of events, called septic shock syndrome, leading to organ failure and death.

The presence of endotoxin in the blood -- endotoxemia -- is associated with a bacterial infection that frequently occurs as a complication of prolonged hospital stays, major surgery or therapies that weaken the immune system. "Current treatment consists of an intensive antibiotic regimen," notes Incyte's vice president of research, Dr. Randy Scott. "This therapy addresses the bacterial infection but doesn't prevent the destructive action of endotoxin. In fact, the very act of killing the bacteria can release more endotoxin into the body, triggering disseminated intravascular coagulation, adult respiratory distress syndrome, acute kidney failure and other severe reactions that are symptomatic of irreversible shock. BPI offers a potential solution by focusing directly on the endotoxin."

BPI is normally produced by the human immune system and is contained within protein packages, called granules, in certain types of white blood cells. Preclinical pharmacology and toxicology studies by Incyte researchers indicate that BPI, unlike antibodies under development by other companies, appears to bind to endotoxins from a broad variety of gram-negative bacteria. If these results can be duplicated in human clinical trials without significant adverse side effects, BPI may prove to be a more widely effective therapy for gram-negative septic shock than antibody-based pharmaceuticals, which offer the promise of reduced mortality but appear to be effective in less than half of the patients treated.

"BPI is a striking example of the commercial potential of granule proteins," notes Roy Whitfield, president of Incyte. "The medical community has a significant need for such a product. Now, with the resources offered by Genentech, we are in a position to speed up our development activities."

Preclinical results to date are encouraging. At a recent meeting of the International Shock Society in Vienna, Austria, Incyte's lead collaborator, Dr. Charles Fisher, director of the Center for Critical Care Research, University Hospitals of Cleveland, and associate professor at Case Western Reserve University, presented data showing that BPI is able to protect animals from lethal doses of endotoxin. It is important to recognize, however, that additional animal experiments and several years of human clinical studies are required to prove the safety and effectiveness of BPI before it will be commercially available.

Incyte Pharmaceuticals Inc. is a privately held biotechnology company focusing on granule protein biology and the development of a new generation of therapeutic products for inflammatory and degenerative diseases. The company is headquartered in Palo Alto, California.

Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant medical needs. The company has headquarters in South San Francisco, California.

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