West Coast Editor

Privately held Receptor BioLogix Inc. pulled down $33.6 million in a Series A financing to boost Dimercept, its cancer drug readying for Phase I trials next year.

Existing cash will "get us to the middle of Phase II trials, according to our plan," said Michael Shepard, president and CEO of South San Francisco-based Receptor.

"We'll start the Phase I trials in the second half of 2006, and we'll start the Phase II sometime in the second half of 2007," he added.

Dimercept, formerly known as Herstatin, is described as a broad-spectrum cancer agent representing a new class of biotherapeutics called intron fusion proteins that modulate pathways in cancer, inflammatory and autoimmune diseases.

The new name better characterizes the drug, which Shepard called a "pan-specific antibody" that binds to the dimerization domain - the place where molecules join - on the receptor. Phase I multiple-dose trials will test the drug in cancers that overexpress human epidermal growth factor, a category that includes more than half of all solid cancers, such as those of the lung, prostate and breast.

"The big advantage of antibodies is that they're very specific and they don't have much toxicity," Shepard said. "They're good molecules. A downside is that they bind only their own cognate receptor, but usually two or more are being co-expressed half the time."

Dimercept, by contrast, blocks activation of the entire family of epidermal growth factor cell receptors, including the well-known HER-2 receptor.

"It's like having two or three accelerators pushed all the way to the floor," Shepard said. "If you take one away, you still have two."

EGFR drugs, of course, include the blockbusters Erbitux (cetuximab) for colorectal cancer from ImClone Systems Inc. and Bristol-Myers Squibb Co., both of New York, and Herceptin (trastuzumab), from South San Francisco-based Genentech Inc.

Shepard was a co-discoverer of Herceptin, which sold $129.6 million in the first quarter for Genentech, at which he worked from 1980 to 1992.

"I'm not doing anything to trash Herceptin, but it's only good for a maximum of 25 percent of breast cancer patients," he said. "We would like to do a lot better than that."

Preclinical research indicated Dimercept targets and blocks all members of the family's receptors - HER-1 (EGFR-1), HER-2, HER-3 and HER-4 - and the drug has proved effective in animal models of prostate, gastric, ovarian and brain cancers (all of which express multiple HER family members). Receptor is extending its investigations to lung cancer and other malignancies.

Highest on the list are pancreatic, non-small-cell lung, esophagus, gastric and liver cancers, Shepard said.

At least two big-pharma players also are trying to cast a wider HER net. London-based GlaxoSmithKline plc has the dual-kinase drug lapatinib, which hits EGFR and HER-2, in Phase III trials for breast cancer. Shepard said that compound might prove formidable, "but we don't know yet if it suffers from the same issues of Iressa, where it's only hitting a small percentage of the receptors" - about 10 percent of subtypes.

Iressa (gefitinib) from AstraZeneca plc, of London, was approved in the spring of 2003 for NSCLC on the basis of tumor response rate. In a subsequently reported trial that enrolled 1,692 subjects, however, Iressa as monotherapy failed to show a survival benefit vs. placebo in the overall NSCLC patient population or in those with adenocarcinoma, a tumor that originates in glandular tissue. (See BioWorld Today, Dec. 20, 2004.)

The GSK compound may be "comparable somehow" to Receptor's drug, "but it's a small molecule, so it's inhibiting kinase activity directly," meaning the frequency of resistance is going to be pretty high, Shepard said.

Wyeth, of Madison, N.J., also is working on a multiple-target inhibitor that is "more mysterious" in the same area, he said.

Key venture investors in Receptor's Series A included Skyline Ventures, of Palo Alto, Calif. (which led the syndicate); Domain Associates, of Princeton, N.J.; Essex Woodlands Health Ventures, of The Woodlands, Texas; MedImmune Ventures, of Gaithersburg, Md.; Takeda Research Investment Inc., a wholly owned subsidiary of New York-based Takeda America Holdings Inc.; and Northwest Technology Ventures, of Portland, Ore.

Shepard said there have been some talks about raising more money, and a few preliminary discussions regarding potential partners, "but we don't have to worry about that too much right now. We don't plan to do anything at least until after we have Phase I [data]," he said.