BioWorld International Correspondent

LONDON - A start-up formed around technology from Baylor College of Medicine in Houston has made its home in Cambridge, UK. Ceros Ltd. said it will fill the biology gap that has developed between high-throughput genomics technologies and the identification of therapeutically useful targets.

CEO Sohaila Rastan told BioWorld International, "We will take targets from the genome and build up a complete understanding first of the biology, and more importantly, the pathophysiology." The company is concentrating on discovering targets and drugs for indications related to the functions of the hypothalamus, which Rastan described as "an extremely rich fishing ground."

The initial focus will be on osteoporosis, building on the discovery by one of Ceros" co-founders, Gerard Karsenty, that bone formation is under hypothalamic control. This overturned the traditional view that bone cells (osteoblasts and osteoclasts) control bone formation locally. Furthermore, Karsenty, with Patricia Ducy, also a Ceros co-founder, discovered that the hormone leptin is an inhibitor of bone formation.

"We have extremely good biological data, and the evidence is stacking up nicely that inhibiting the leptin pathway increases bone formation," Rastan said. "We are looking at developing the first anabolic drug to increase bone mass. All the drugs available at present [for treating osteoporosis] aim to prevent bone loss. This is like putting out the fire; what we want to do is repair the damage."

Leptin is expressed by fat-forming adipocytes and acts through the hypothalamus to control body weight, eating behavior and reproductive development. Rastan said a number of groups are working on leptin as a treatment for obesity.

Ceros wants to set up collaborations with pharmaceutical companies that have programs in leptin and related pathways. "We are getting a relatively high amount of interest from pharma," Rastan said. "We want to have the flexibility to partner when appropriate.

"Leptin and leptin mimetics have been disappointing in the clinic. We think this is because the primary biological indication is bone, not fat." Crucially, however, the effect on bone comes before, and at lower doses than the effect leptin has on weight, indicating that leptin inhibition will not cause obesity. "There are two separate phenotypes. We have very nice data showing the two are physiologically separate," Rastan said. Reducing leptin levels in mice by 50 percent increased bone density by 63 percent.

Ceros also plans to exploit the leptin pathway to find treatments for obesity and Type II diabetes.

Ceros was founded in March 2000 as a spin-off from Baylor, and received incubator funding from the college's technology transfer arm, Baylor College of Medicine Technology. Up to January 2001 it raised US$1.85 million from Baylor and a variety of private investors. Rastan is now talking to venture capital investors in the U.S. and the UK with the aim of raising $15 million to $20 million by the end of August, enough money for 3.5 years, enabling Ceros to increase staff numbers from nine to 25, and to have a protein therapeutic and a small-molecule inhibitor of leptin in the clinic.

Rastan joined the company as CEO in November 2000 from SmithKlineBeecham plc, where she was senior director of biotechnology and genetics. It was decided to base Ceros in the UK because she lives here, and another co-founder, Allan Bradley, professor of molecular and human genetics at Baylor and founder of Lexicon Genetics Inc., was returning to the UK to take up the directorship of the Sanger Centre, the UK center for sequencing the human genome. Bradley is now charged with moving research there from sequencing to functional analysis.

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