Quark Biotech generates a cholesterol-free mouse

December 18, 2003

Fremont, CA - December 18, 2003 - Quark Biotech, Inc. (QBI) today announced the publication in the prestigious peer reviewed scientific journal, Science, the results of a study of mice that contain virtually no cholesterol. The study was conducted together with scientists from the Karolinska Institute in Sweden and the Sackler School of Medicine in Israel. This mouse strain was created by disrupting the gene Dhcr24, which encodes the enzyme called desmosterol reductase and appears to be responsible for the last step in the biosynthesis of cholesterol, a sterol that is an indispensable structural block of cells and their membranes and plays major roles in signal transduction. The paper entitled "Generation of Viable Cholesterol-Free Mice," appears in Science, December 19, 2003 (Vol. 302, Page 2087).

"We were surprised by the fact that a mouse lacking cholesterol can survive and develop into adulthood with little effect, when cholesterol accounts for approximately 99% of all steroids in mammals," commented Dr. Elena Feinstein, VP of Technology Development at Quark Biotech and senior author of the study. "We believe that this mouse can become a highly resourceful tool to further understand the role of cholesterol in the different organs. This knowledge can in the future help discover novel drugs and understand the mechanism of action of existing drugs for metabolic diseases and cancer, among others."

The study supports for the first time in a complex organisms model the "sterol synergism" theory, which points out the interchangeability of certain sterols, that up to now had only been shown in simple models such as yeast. However, the research conducted suggests the importance of cholesterol in the developmental stages, particularly during embryogenesis. Furthermore, the knock-out pups appeared to be smaller in size and showed poorer growth characteristics than the normal animals.

Dr. Daniel Zurr, CEO of Quark Biotech said, "Quark initiates drug discovery programs accordingly to preset clinical endpoints. This study is a clear example to our commitment to understanding the root of the diseases. We believe that this cholesterol-free model will bring additional intelligence on how the body behaves, providing us with novel treatment endpoints suitable for novel strategies of drug discovery, for instance, for metabolic diseases."

The resulting mild effects of the disruption of desmosterol reductase in this model contrasts dramatically with the autosomal recessive malformation syndrome resulting from a deficiency of this enzyme named desmosterolosis. Since only two cases have been identified, the desmosterolosis phenotype has yet to be fully delineated. However, it appears that during embriogenesis, rodents benefit from the cholesterol synthesized by mother, while humans' maternal cholesterol is not available at these early developmental stages.
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About Quark Biotech

Quark Biotech, Inc., a privately held company headquartered in Fremont, CA, is pioneering Endpoint Driven Drug Development (ED3). ED3 is a vertically integrated drug development approach that starts with defining a desired clinical endpoint in any specified disease to design drug candidates to achieve the defined endpoint. Quark's approach uncovers the critical gene and protein functions profoundly affecting relevant disease pathways allowing the company to develop conceptually novel drugs that provide previously unavailable benefits to patients. The Company currently focuses on developing therapeutics to treat metabolic disorders, cancer, and renal diseases in parallel to the ongoing pharmaceutical collaborations in other disease areas. Quark's lead molecule is in Phase II studies to treat dyslipidemia/metabolic syndrome. Quark's global team of researchers consists of approximately 200 employees, in research facilities in Fremont, California, and Ness-Ziona, Israel. Quark has recently consolidated all its U.S. operations to its new Fremont, CA headquarters, housing the Corporate Product Development unit, Discovery and Microarray facility, Technology Development unit, and Corporate Finance and Business Development department. Additional information is available at www.quarkbiotech.com.

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