Start-up Profiles

Published online: 26 April 2004, doi:10.1038/bioent804

Can-Fite BioPharma

Putting some muscle into the fight against cancer.

Israeli company Can-Fite approaches cancer and inflammatory disease treatment based on the observation that "cancer metastases rarely go to muscle tissue," explains CSO Pnina Fishman. In the mid-1990s, Fishman, then a scientist at the Rabin Medical Center (Petah Tikva, Israel), discovered that muscles secrete small molecules that stop cancer cells from growing.

Fishman found that these small molecules are agonists and exert their actions by binding to a specific cell surface receptor—the A3 adenosine receptor (Cancer Res.  58, 3181-3187, 1998). She subsequently found that these receptors are overexpressed in tumor cells. She deduced that a molecule targeting this receptor could be a promising anticancer drug candidate.

After a literature search, Fishman identified a group of small molecules with a high affinity and specificity to this receptor, which were synthesized and patented by Kenneth Jacobson, head of the molecular recognition section of the National Institute of Diabetes & Digestive & Kidney Diseases at the National Institutes of Health (NIH; Bethesda, MD, USA). She obtained an exclusive license for the patent covering the group of molecules and together with Ilan Cohn, a prominent Israeli intellectual property attorney, launched Can-Fite in 2000 (see Can-Fite profile).

In addition to the in-licensed 'composition of matter' patents from the NIH, Fishman and Can-Fite patented the use of small molecules called IB-MECA and Cl-IB-MECA (now designated CF101 and CF102, respectively) for the treatment not only of cancer, but also of inflammatory/autoimmune diseases (see below). And so far, direct competitors are few and far between; the company claims that no other company is targeting A3 adenosine receptors for application in oncology and inflammatory/autoimmune disease. Pfizer (New York), however, does have a drug development program based on the A3 receptor for cardiology applications.

To bolster its pipeline, Can-Fite pursued the research collaborations established by its scientists before the creation of the company. These include collaborations with the NIH established in 1998 and with the Leiden-Amsterdam Drug Research Center at Leiden University in The Netherlands since 2001. Through these collaborations, the company has further identified other A3 adenosine receptor agonists (including CF402) that are potential drug candidates.

The company's scientists have also explored the molecular mechanism of action of their lead candidate, CF101, in different diseases. In cancer, CF101 binds adenosine receptors and thereby downregulates several important signaling molecules, including Wnt and the nuclear factor (NF)-kappaB, which are pivotal in the control of the growth of tumor cells. By intervening in signaling through these pathways, Can-Fite scientists hope to prevent overexpression of A3 receptors on cells, thereby inhibiting metastatic growth.

Can-Fite scientists also believe that CF101 has potential in autoimmune/inflammatory disease because downregulation of the transcription factor NF-kappaB also suppresses expression of tumor necrosis factor (TNF). TNF mediates many of the inflammatory responses in diseases like rheumatoid arthritis and anti-TNF drugs, such as Johnson & Johnson's Remicade (infliximab; New Brunswick, NJ, USA), Amgen's Enbrel (etanercept; Thousand Oaks, CA, USA) and Abbott's Humira (adalimumab; Deerfield Park, IL, USA), are already in wide use for the treatment of rheumatoid arthritis. All of these latter therapies are expensive protein drugs that have to be administered by injection. In contrast, CF101 is a lower cost oral drug given in the form of a pill or capsule.

So far, the company's pipeline contains one clinical stage product, CF101, which is in phase 2 clinical trials for both refractory metastatic cancer and rheumatoid arthritis. The company is finalizing plans to begin its first Investigational New Drug (IND) phase 1 study of CF101 in combination with chemotherapy to begin in the second quarter of 2004. "We're shifting most of our development to the United States because our clinical development will be there," explains Cohn, Can-Fite's CEO.