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Nov 25, 2002
 |  BioCentury  |  Product Development

Telik's sensitive situation

With maturing Phase II cancer data in hand for its TLK286, Telik Inc. is preparing to start Phase III trials in advanced ovarian cancer in the first quarter next year. The company believes that TLK286's mechanism makes it particularly amenable to chemotherapy-resistant tumors, thus providing the potential for a single agent salvage therapy.

TLK286 is a small molecule that is activated by glutathione S-transferase (GST) P1-1, which is highly expressed in most cancers. Levels of the enzyme become even higher following chemotherapy, and are thought to contribute to resistance to such drugs. "Tumors that don't respond to a standard agent may become more resistant to chemotherapy but more sensitive to our compound," said Gail Brown, senior vice president and chief medical officer.

Once activated, two fragments of TLK286 break off and trigger apoptosis through the stress response kinase pathway, which involves the activation of two kinases - MEK4 and JNJ1 - and caspase 3. According to Brown, TLK286 "is the only drug activated by GSP P1-1 and the only drug that works via the stress response kinase pathway to apoptosis."

TELK (South San Francisco, Calif.) last week reported additional data from two Phase II trials of the compound in ovarian cancer and non-small cell lung cancer. The company also reported Phase II data in advanced colorectal cancer. In the Phase II ovarian trial in 36 patients, median survival in the TLK286 group had not yet been reached after more than 16 months. Using standard treatments, median survival in this patient population would be about...

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