Cyclis Pharmaceuticals Inc. is banking on its activated checkpoint therapy to fight cancer.

The Norwood, Mass.-based company, founded by CEO Samuel Ackerman and other members of the management team in the fourth quarter of 2001, is gearing up to enter its first compound in the clinic by mid-2003.

"The most important concept about the company is that we believe our technology offers the potential to offer improvements in the efficacy and safety of current cancer therapy," Ackerman told BioWorld Today.

Privately held Cyclis said last week it raised $5 million in its first round, all of which came from Wellesley, Mass.-based Ampersand Ventures. Cyclis expects to raise an additional $7.5 million from new investors before the round closes in the fourth quarter, Ackerman said.

Cyclis' technology is based on cell cycle research, focusing on the mechanism by which cells check for genetic damage, called a checkpoint. Checkpoint therapy is designed to restore apoptosis and checkpoint functions that are lost during carcinogenesis, the company said. Cyclis said cancer cells are allowed to proliferate because several key checkpoint and apoptotic pathways are disabled during the development of cancer.

Cyclis has three drug discovery programs targeting major pathways controlling checkpoints and apoptosis. The programs are in E2F modulation, transcription factor modulation and p53 modulation.

Its lead clinical candidate is CO-501, a compound that activates a cellular checkpoint and provides an apoptotic stimulus to cancer cells without damaging the cell's DNA, the company said. It is scheduled to enter Phase I studies in mid-2003 for the treatment of solid tumors.

Cyclis has conducted preclinical studies of CO-501 in combination with Taxol that show the combination has improved effects over either agent administered as a monotherapy, Cyclis said. The CO-501 technology originated in the lab of Arthur Pardee, a professor of biological chemistry and molecular pharmacology emeritus at the Dana-Farber Cancer Institute and Harvard Medical School. Pardee is a member of Cyclis' scientific advisory board. Much of the research in Pardee's lab was conducted by Chiang Li, who is now vice president of research at Cyclis.

A second program, TF modulation, is designed to inhibit activation of other selected nuclear transcription factors in order to trigger apoptosis in cancer cells. The p53 modulation program was recently acquired from Johns Hopkins University, which discovered a new intracellular protein called PUMA (p53-Upregulated Modulator of Apoptosis). Cyclis has worldwide exclusive rights for the program.

Cyclis plans to take a second compound into the clinic in 2004. The company's strategy is to develop its compounds through pivotal clinical trials and retain North American rights, Ackerman said. Cyclis is in discussions with "a number of groups," he said, regarding potential partnerships.

"Broadly speaking, we're interested in partnerships with groups who would like to market our products in Europe and Asia," Ackerman said.

The company plans to secure a partnership by year's end, he said, making it Cyclis' first.

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