Plans to push its lead compound into a Phase III trial has Telik Inc. beaming like a proud parent at a child's graduation.

The Palo Alto, Calif.-based company began a randomized, controlled, registration study of TLK286 as a single agent in ovarian cancer patients whose disease has progressed despite prior treatment with platinum-based chemotherapy and a second-line treatment.

"A lot of people have worked very hard for this," Telik CEO and Chairman Michael Wick told BioWorld Today, adding that the trial's therapeutic indication has been dictated, in part, by the compound's interaction with an enzyme found in high concentration within ovarian cancer cells. "It is administered to patients in an inactive form, and activated within the tumor cell, making it much safer and better tolerated because it does not damage normal tissue."

Specifically, the prodrug is activated by the enzyme GST P1-1, the presence of which is detected in ovarian, breast, lung and colon cancers. Telik has completed Phase II studies of TLK286 in the latter three cancers as well, but ovarian cancer has stood out as the compound's lead indication.

"Ovarian cancer has the highest mortality rate among all gynecological cancers," Wick said. "There is an important need, because in general, ovarian cancer has spread by the time it is diagnosed."

Called ASSIST-1 (assessment of survival in solid tumors-1), the trial is expected to enroll about 440 women in North and South America as well as Europe. Patients will be randomized to receive either TLK286 or a control drug, either Doxil or Hycamtin. Both drugs are commonly used in the third-line ovarian cancer setting.

Accrual could take up to about 15 months for the study, which is designed to evaluate whether Telik's small molecule reduces the risk of death, leading to an increase in survival, compared to control.

The company's stock (NASDAQ:TELK) climbed 86 cents on Thursday's news to close at $13.23, also up from a public offering price from last fall. Telik grossed $74.75 million through the public sale of 6.5 million shares priced at $11.50 apiece. (See BioWorld Today, Sept. 30, 2002.)

A large portion of the funding was directed toward advancing TLK286 into the Phase III program. Telik, which maintains full worldwide commercialization rights to the compound, aims to extract value from its North American rights.

"We must end up with significant commercial rights in North America, as we do intend to be a commercial enterprise," Wick said. "Anything that supports that, we are prepared to discuss and entertain. You can keep the rest of the world."

Data from multiple Phase II trials of TLK286 first presented last spring and again in the fall supported a nod from the FDA for Telik to move forward into a Phase III program. At the time the agency gave Telik the go-ahead to proceed with a Phase III registration trial in non-small-cell lung cancer.

The company plans to eventually further study the drug in such an added indication, though Wick declined to specify a timeline.

Preliminary results from a study of advanced, platinum-resistant, non-small-cell lung cancer patients reported at May's American Society of Clinical Oncology meeting showed single-agent antitumor activity. Data from another Phase II trial pointed to significant single-agent activity in advanced ovarian cancer.

At November's Symposium on Molecular Targets and Cancer Therapeutics in Germany, Telik offered further Phase II data in addition to preclinical findings of TLK286 given in combination with chemotherapeutic drugs.

At the time, Telik said median survival exceeded 16 months in 63 percent of 36 patients in the ovarian cancer trial to date. The lung cancer trial demonstrated a median survival of nine months, with 38 percent of patients alive at one year. In a refractory colorectal cancer trial involving 73 patients who had failed 5-fluorouracil, leucovorin and irinotecan chemotherapy, TLK286 treatment resulted in a median time to tumor progression of 2.9 months, an increase over both oxaliplatin (1.6 months) and 5-FU/LV (2.7 months). The drug also showed an improvement in median survival time.

Preclinical findings pointing to an enhancement of cytotoxicity were seen when TLK286 was combined with anticancer agents including doxorubicin, carboplatin, docetaxel and oxaliplatin. (See BioWorld Today, Nov. 21, 2002.)

Wick said Telik would present new data on TLK286 in treating breast cancer during the American Society of Clinical Oncology meeting scheduled to begin in late May in Chicago.

Beyond spending on TLK286, Telik also has applied a share of its recent financing toward deeper pipeline progression. Wick said the company would present at next month's American Association for Cancer Research meeting in Toronto, Phase II results of its TLK199 compound. Preliminary positive data have pointed to the candidate's effectiveness in stimulating white blood cell production in patients with myelodysplastic syndrome.

Telik also continues to develop TLK19781, an orally active compound designed to activate insulin receptors for diabetes.