West Coast Editor

Receptor BioLogix Inc. bought bankrupt Aphton Corp.'s failed Phase III drug Insegia for $750,000, and hopes to make the gastrin-targeting antibody stimulator work against stomach and pancreatic tumors.

"We haven't fully decided all of our clinical strategy, so I don't know that I can get into that," said Thomas Glaze, CEO of South San Francisco-based Receptor. "We have our work cut out for us, but I think we have a good asset that patients need."

Insegia, by taking aim at gastrin, generates antibodies to the growth hormone and its receptor, which could neutralize the hormone's ability to help cancers grow - in theory, at least.

Also known as G17DT, the compound missed its primary endpoint early last year by not improving overall survival of patients when used in combination with gemcitabine, sold as Gemzar by Indianapolis-based Eli Lilly and Co. (See BioWorld Today, Feb. 16, 2005.)

Results looked encouraging, though, in antibody responders, who represented 70 percent of those in the Insegia treatment group and who were said to have achieved a "clinically meaningful difference" in survival. That difference didn't stop Sanofi Pasteur, of Lyon, France, from backing out of its marketing deal with Aphton - a move that came partly because Sanofi (still Aventis Pasteur when the deal was signed in 1997) had just been acquired by Paris-based Aventis Group, which had other priorities. Aphton filed for bankruptcy in May. (See BioWorld Today, Nov. 11, 2005, and May 25, 2006.)

Some might have thought Aphton, of Philadelphia, made a strange choice in pairing Insegia with Gemzar, since Insegia demands an immune response and Gemzar suppresses the immune system. The company apparently believed a high enough dose of Insegia would overcome the other drug's effects. It didn't work - not well enough.

"There might have been a better alternative," acknowledged Glaze. "We don't know all the history, and we're not going to try to dredge all that up."

The trial was formulated with guidance from the FDA years ago, he noted, and regulators might be open to a potentially more successful design. Glaze pointed to better data (though again a missed endpoint) from the Phase III trial with Insegia as a monotherapy in Europe, and to promising results from another, recently published study in stomach cancer when paired with 5FU.

Overseas, the picture might be even brighter. A new option for conditional approval, followed by Phase IV trials, anticipates "situations like this, where you have a drug that's generally safe, and there are indications of efficacy, though not proved by normal standards," he said.

The Insegia opportunity came to light through one of Receptor's venture capital investors who "had been familiar with the Aphton situation, and had been looking at them as a potential investment, and decided not to do that," Glaze said. Aphton's bid for more money fell through at the last minute, which led to the bankruptcy.

"We've had to do a sort of crash program to understand and do the due diligence on [Insegia], which we've been doing since late May," he added.

Receptor's own lead compound is Dimercept, formerly known as Herstatin, a broad-spectrum cancer agent and member of the intron fusion protein class, which modulates pathways in cancer, inflammatory and autoimmune diseases.

Described as a pan-specific antibody that binds to the dimerization domain (where molecules join) on the receptor, Dimercept is being tried against 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.

Preclinical work showed Dimercept targets and blocks all members of the family's receptors, including HER-1 (EGFR-1), HER-2, HER-3 and HER-4. The drug has proved effective in animal models of prostate, gastric, ovarian and brain cancers (all of which express multiple HER family members).

"We're targeting to be in the clinic with a pan-HER molecule in early 2008," Glaze said, noting that the molecule might not be Dimercept.

"We have some other alternatives, and we anticipate making a selection by the end of this year," he said. "The vision is still the same."

Aphton's stock (Pink Sheets:APHT) closed Monday at 1.7 cents.