Can-Fite’s CF-101 is intended as a long-term treatment to prevent cancer from worsening.An Israeli startup known as Can-Fite Biopharma is reversing the normal approach to developing drugs in the laboratory: Instead of looking for why cancer occurs, it’s trying to find out why cancer cells almost never grow in muscle tissue, which makes up 65 percent of the human body.

The inspiration for the approach and for the Petah Tikva, Israel, company came from a challenge Can-Fite co-founder Pnina Fishman received from one of her teachers.

“One day, he came and told me, ‘Muscles are 65 percent of body mass, but cancerous tumors are rare in muscle tissue. Why?'” Fishman said. “He threw me the ball, and I ran with it. The whole world is asking why there is cancer. We asked why there wasn’t.”

After doing tests on cultures, Fishman concluded that certain substances secreted by the muscles differentiate between cancerous and normal cells and restrict the development of the cancer cells, while leaving normal cells untouched. She also discovered that these defensive substances protect white blood cells from damage caused by chemotherapy.

One of the substances involved in the process is called adenosine, a molecule present in all tissue cells, which guards against cancer by linking receptors. Fishman found that the receptor that activates the anti-cancer mechanism is what’s known as an A3 receptor. These receptors can be activated by synthetic molecules that bind with them.

To further their research, Fishman obtained two of these binding molecules from the National Institutes of Health in the United States under an exclusive license.

Unlike adenosine, which breaks down in the bloodstream within 20 seconds and can be toxic in high concentrations, the synthesized molecules remain in the body for eight hours, and are not toxic.

“Basically, we’ve found a molecule that can differentiate between cancer cells and normal cells,” Fishman said.

CF-101, Can-Fite’s anti-cancer drug created from the molecule, is scheduled to begin Phase I clinical trials in February. CF-101 is not a 100 percent cure, but a long-term treatment to prevent cancer from worsening, turning it into a chronic illness that can be lived with for years, such as asthma.

Clinical trials on mice produced impressive results by combining CF-101 with chemotherapy. Regulators will probably consider the drug as a supplementary, rather than as a stand-alone treatment, which would make it less difficult to get marketing approval, said Can-Fite President and co-founder Ilan Cohn.

Can-Fite has scheduled Phase II trials for CF-101 for the end of this year or early 2003.

Earlier research proved that the molecules could also protect against damage to the heart and neurological systems, which could lead to additional applications. Can-Fite is also developing treatments for viral diseases, Alzheimer’s, and various infections and is collaborating with Temple University in Philadelphia to exploit the molecule’s anti-viral potential to prevent certain types of AIDS-related infections.

Fishman was a researcher at the Felsenstein Medical Research Center of the Rabin Medical Center in Tel Aviv. In 1994, she founded Mor Research Applications, a subsidiary of the Kupat Holim Clalit HMO, which now holds a small stake in Can-Fite.

Can-Fite’s new research laboratories in Petah Tikva are scheduled to open in August.

The company’s recently raised $10 million in a round of venture capital financing led by Israel’s Giza Venture Capital. Can-Fite previously raised $4.1 million, including $3.5 million from external sources, and $600,000 from internal sources, including a personal investment by Cohn.

“I hope to see Can-Fite as a second Teva, not in terms of size or focus, but in terms of its global impact,” Cohn said.