By Frances Bishopp

Genomics company Variagenics Inc., which focuses on genetic variances among humans as the basis of its drug discovery efforts, has raised $12.1 million in a private financing.

Participants in the financing include the Cambridge, Mass., company's founding investor, Kummell Investments, of Hong Kong, as well as new investors Atlas Venture, of Boston, Forward Venture, of San Diego, Oxford Bioscience Partners, of Westport, Conn., Advent International, of Boston, and Goldman Sachs, of New York.

"We believe the most interesting information coming out of genomics has to do with human diversity," Fred Ledley, president of Variagenics, told BioWorld Today. "One in 300 bases in the genome is variable. Coming to grips with that variability is very important to the pharmaceutical industry.

"One of the things which differentiates this company from other companies which also talk about pharmacogenomics is our technology. Variagenic Targeting allows us to discover drugs which take advantage of this variation," Ledley said.

Variagenics' core technology and strategy for drug discovery, Variagenic Targeting, exploits the absolute and consistent genetic differences between cancer cells and normal cells, caused by the loss of variant forms of essential genes, to achieve selective killing of cancer cells, Ledley said. This method, he added, is potentially an enormously powerful approach to treating cancer, but can also be applied to other non-malignant proliferative diseases.

The concept of Variagenic Targeting is based on the fact that every normal cell in the body has two copies of every gene: one from each parent, Ledley explained. During the origin of a cancer, one of those genes is frequently lost; therefore, in a cancer, all of the cells in the cancer will have lost one parental copy of probably 30 to 40 percent of all their genes. The technical name for this is loss of heterozygosity (LOH).

If genes can be identified that have three criteria -- essential for cell survival, exist in two distinguishable forms, and are subject to loss of heterozygosity -- a situation is created where a drug that inhibits one parental form will kill the cancer cell, Ledley said.

"The cancer cell would have only one form of the gene and we know that gene is essential for cell survival," Ledley said. "The normal cell won't be killed."

Fifteen Potential Targets Already Found

To date, Variagenics has identified 15 targets, which, Ledley said, are essential and exist in two different forms so that half the people in the population will have one of each.

"We are not going for rare individuals here," Ledley said. "We are going for half the people in the world with lung cancer, for example. We know these are common variances," he said, "and we know that those particular genes very frequently have this loss of heterozygosity in common cancers."

If a specific inhibitor of one form and not the other is developed, drugs could be highly effective in ablating cancers with a high degree of safety, Ledley said.

The difference between the cancer cell and the normal cell is black and white, he continued: the parental copy of that gene is either present or it's not. Virtually all targets for cancer therapy today are relative targets; for example cancer cells grow faster or some protein is expressed at a higher level.

"We see this as a very broad platform technology that will grow primarily through corporate alliances," Ledley said. "We believe our technology will be very attractive for helping the pharmaceutical industry generate value out of genomics."

Privately held Variagenics was founded in 1993 under the name K.O. Technology. Seed money was provided by Kummell.

Variagenics has a collaboration with Isis Pharmaceuticals Inc., of Carlsbad, Calif. Ledley estimates this financing will bring the company through mid-1999. *