BioWorld International Correspondent

LONDON - Enact Pharma plc said it acquired marketing rights to CPG2 for the treatment of methotrexate toxicity from the Centre for Applied Microbiology and Research (CAMR) and is now ready to file for U.S. and European marketing approval of the product.

Methotrexate is a cytoxic frequently used in cancer chemotherapy, but in 1.5 percent of cases it induces kidney failure, for which there is no treatment. Since 1997, more than 200 patients who experienced this toxicity have been successfully treated without serious side effects, in trials carried out in collaboration with the U.S. National Cancer Institute and groups in Bonn, Germany, and Berlin. Enact expects to launch CPG2 (carboxypeptidase G2) in 2004.

That marks the culmination of almost 30 years of research for Tony Atkinson, CEO of Enact, who started investigating CPG2 in 1973 with the aid of a grant from the Cancer Research Campaign. He was then an employee of the UK government's Microbial Research Establishment, the forerunner of CAMR. Roger Melton, who also worked on CPG2 at CAMR and is now director of biotechnology at Enact, said, "It is immensely gratifying to be able to see many years of hard work and research culminating in a product which brings real and immediate benefits to patients."

After administration, methotrexate is metabolized to 7-hydroxymethotrexate, which precipitates in the kidneys. In the trials a single dose of CPG2 reduced serum methotrexate levels by around 98 percent within 15 minutes of administration, with no serious side effects. If it is administered within 72 hours of onset of intoxication, most patients go on to make a full recovery.

The company said it believes the availability of an antidote would enhance the therapeutic potential of methotrexate by allowing clinicians to increase the dosage.

Based on current therapeutic use, Enact predicts sales of over £1 million (US$1.46 million ) in the first year, rising to £5 million to £7 million within three years. The company said that would give it the resources to go ahead with Phase I trials of its first in-house-developed product, NQ02, a cancer treatment.

Enact was founded as Enzacta Ltd. in 1998 with £2 million from the venture capital company 3i plc, to develop antibody-directed enzyme prodrug therapies to treat cancer. Its founder, Jon Dickens, was formerly technical director of Chiroscience plc (which merged with Celltech plc) and a founder of British Biotech plc.

CPG2 came into the portfolio in April 2000 when Enzacta merged with Kymed Ltd., a spinout of CAMR. Enact is quoted on London's Ofex over-the-counter market and has raised a total of £6.2 million.