Editor

Telik Inc. is on the march.

And has been for some time, the company might say, having changed its name in 1998 from Terrapin Technologies Inc. The replacement moniker is a variation of the Greek word "telic," which means moving purposefully toward a goal.

Last week, though, Telik disclosed news investors might have found particularly indicative of advancement. The company said it will start before the end of the year a second Phase III trial with Telcyta (TLK286), this one against non-small-cell lung cancer and called ASSIST-2, which stands for Assessment of Survival In Solid Tumors-2.

Already under way is ASSIST-1, testing Telcyta in ovarian cancer.

The new trial will enroll about 500 patients with platinum-refractory or resistant NSCLC, randomized to get either Telcyta or Iressa (gefitinib) for the third-line treatment of the cancer.

Iressa is London-based AstraZeneca plc's headline-making NSCLC treatment approved earlier this year, and the study will test whether Telcyta (which is unpartnered) leads to increased survival. Iressa has failed to show a survival benefit, fizzling in a Phase III trial against NSCLC in 2002. But the drug won marketing approval anyway, based on a 10 percent response rate in a Phase II study.

Easy target? Could be. Iressa is an endothelial growth factor receptor (EGFR) inhibitor - like Tarceva (erlotinib), which also failed last week in two Phase III trials testing it in combination with chemotherapy for NSCLC. Tarceva is the subject of a three-way deal between Genentech Inc., OSI Pharmaceuticals Inc. and Roche Holdings Inc.

Telcyta, on the other hand, is a small-molecule prodrug that leads to apoptosis when activated by GST P1-1, an enzyme present in higher levels in many human cancers than in normal tissues. Telik has gained a special protocol assessment from the FDA for both trials, said to lessen the regulatory risk. And the drug so far has shown efficacy in four types of cancer in 10 trials, with a safety profile described as benign.

"A year and a half ago, I think this was still a maturing story," said Jim Birchenough, analyst with Lehman Brothers. "We had some early data that were promising, but it's really been since ASCO this year that the data set has matured."

Neither Birchenough nor his family owns Telik stock, but Lehman Brothers has a banking relationship with the firm. Telik, Birchenough told BioWorld Financial Watch, "has been firing on all cylinders," and Telcyta could be the next wave in cancer therapy "after EGFR and [vascular endothelial growth factor, or VEGF, inhibitors] have run their course."

The newsmaker in the latter category is Genentech's Avastin (bevacizumab), which also caused a stir at ASCO. Genentech said late last month that its biologics license application had been filed with the FDA, and the drug is expected to hit the market within six months as a first-line therapy for metastatic colorectal cancer.

By Beating Iressa, Telcyta Could Own The Market'

Data offered at the American Society of Clinical Oncology earlier this year suggested Telcyta had "at least comparable activity [to Iressa] but in sicker patients, through third-line patients," Birchenough said.

"There has been, over the last six to 12 months, objective activity shown in a broad group of tumors, which we didn't have before," he said. "They've emerged as one of the up-and-coming oncology stories."

The next step with Telcyta could be another comparison study, he added.

"There's a good chance they will do a head to head against Taxotere as well," Birchenough said. "Both make sense." Taxotere (docetaxel) is Aventis SA's chemotherapeutic for breast cancer and NSCLC, which is being studied in other tumors as well.

Telik's ASSIST-1 trial for ovarian cancer is building on earlier positive Phase II data, of course, but is zeroing in particularly on third-line patients. In Phase II, enrolled patients had failed at least two therapies but sometimes as many as seven. The study began in the third quarter of last year.

ASSIST-2 also is following up good Phase II results, disclosed in August at the 10th World Conference on Lung Cancer in Vancouver, British Columbia. An 11 percent objective response rate was observed in the 19 patients evaluable for efficacy at the time of analysis, with an overall disease stabilization rate of 69 percent. Median survival hasn't yet been reached.

That stabilization rate far surpasses the rate gained by the only approved second-line therapy for NSCLC: Taxotere, which tops out at 36 percent. Here again, the side-effect profile comes into play, with harsh ones recorded by patients on Taxotere as compared with Telcyta.

The attention given Telik's lead drug has pushed into the background the company's Target Related Affinity Profiling (TRAP) chemogenomics technology, which the firm says allows for quicker and more efficient screening of compounds, measuring the binding of a small molecule to a proprietary reference panel of proteins in order to create a profile for each compound.

TRAP, though, means revenue from collaborations to help other efforts along. In the March annual meeting of the American Association for Cancer Research, the company said it has identified small-molecule drug candidates for cancer targets, several of them as a result of collaborations with cancer research centers. In April, Telik formed a TRAP collaboration with F. Hoffmann-La Roche Ltd.

With cash coming in from TRAP, Telik can push not only its lead product but one that's regarded as a would-be blockbuster, farther back in the pipeline: TLK199, a small-molecule bone marrow stimulant in a Phase I/II trial for myelodysplastic syndrome, a form of pre-leukemia. No specifically approved treatment exists now and TLK199 works with the same signaling pathway that is activated by granulocyte colony stimulating factor - like Neupogen (filgrastim), Amgen Inc.'s therapy for neutropenia caused by chemotherapy, a longer-acting version of which is Neulasta (pegfilgrastim). What's more, TLK199 - unpartnered so far - has the potential for oral dosing.

Telik offered encouraging interim data from the Phase I/II trial in the March AACR proceedings and expects to present a bigger picture of the results at the European Organization for Research and Treatment of Cancer (EORTC) meeting in November.

"I think it's a good buy, [going] into that meeting," Birchenough said.

What Telik has established with the Iressa head-to-head trial is that "they're either going to show they're superior in what's evolved to be a standard, or not.

"Anytime you improve survival, you're going to own the market. As with all of these companies, there's a binary event down the road when we get the data. This could be a binary event for EGFR drugs as well," he said.