West Coast Editor

"Targeted antibodies, made fast here" may not sound like the sign you'd see hanging outside an office one day, but that - or something like it - is the goal of Arius Research Inc., which reported making progress toward treating cancer patients with more specific drugs.

"It's not autologous," said Helen Findlay, vice president of Toronto-based Arius, about the company's treatment method. "The idea is not that I would take your tumor and give you your antibody only. We're building a large library of antibodies, and when it comes to treating patients, [the process involves] doing an analysis of what antigens they express and then going to the library. Nobody gets a drug they can't use."

The company's patent, she said, "allows us to develop functional antibodies, defined as being antibodies that have a killing effect on cancer cells by themselves. They're not conjugated to anything. We developed them from human tumor tissues, and the benefit is that the tumor tissues will present a target or antigen in its more native form, so it will be folded the way it would be in the body."

Ultimately, by deploying discovery technology and assays, the company aims to provide more individualized therapy with groups of monoclonal antibodies designed to match the antigen profile of a given patient's disease.

Arius has assembled more than 100 anticancer antibodies so far.

"If you're using a piece of tumor, using a bunch of cells to immunize, then the mouse's immune system will react to a whole lot of different things about that cell," Findlay said. "You'll get a number of antibodies produced," which she described as a kind of "soup" laden with possibilities.

"It's a wide collection of antibodies to a whole lot of proteins," she said. "The tricky thing, of course, is to pick out the ones you want. That's where our technology comes in."

Arius screens "directly for function, for cancer-killing capability. That's the only thing we're interested in," Findlay said - that, and selectivity, so that no normal cells are destroyed, she added.

"We then have a whole panel of different cancers and cell lines we screen the antibody against, to choose the ones that show the most potential," she said.

Last week, at the annual meeting of the International Union Against Cancer in Oslo, Norway, Arius offered positive preclinical data for three monoclonal antibodies: ARH460-16-2 and ARH460-22-1 in breast cancer and ARVitamab in lung cancer.

"Our next big step is to move into the clinic, and we're looking to do that within the next 12 months," Findlay said. "We're also in a financing mode right now, and talking to a number of different partners."

The first two antibodies showed encouraging results in mice implanted with breast cancer tumors. With ARH460-16-2, one tumor "didn't grow at all," Findlay said. Mice treated with a carrier or with another antibody all developed tumors. Arius is studying the pair of antibodies in other types of cancer as well.

Animal results with ARVitamab, the company's lead drug, showed it did better alone at preventing the spread of lung cancer than cisplatin and even worked better than the two drugs combined in the metastasis model.

Half the maximum tolerable dose of cisplatin was used, Findlay told BioWorld Today.

"We think what's happening is that, if the dose of cisplatin isn't enough to do anything by itself, it might be selecting for resistance," she said. "The combination was close to being statistically significant at controlling growth of the originally implanted tumor, but it didn't seem to have the same effect on metastases. We don't have a clear explanation for that."

Specifically, the number of mice with metastasis to either the other lung or lymph system was reduced by 57 percent to 75 percent for mice treated with ARVitamab, compared with the control group. The cisplatin group ended up with only a 2.5 percent to 4 percent reduction in metastasis, and the combined therapy produced a decrease of 21 percent to 44 percent.

ARVitamab recognizes an antigen found in more than half of epithelial cancer tissues and, ultimately, Arius plans to expand research and development into cancers to include gastrointestinal, ovarian and prostate. The company wants to outlicense therapeutic antibodies before Phase III trials would begin, and is seeking partnerships for diagnostics. Antibodies and antigens will be outlicensed as research tools, too, with much marketing of the antibodies aimed at proteomics firms. Arius' first apparently novel antigen is available for outlicensing now.

Founded in August 1999, Arius completed a private financing of about C$3 million (US$1.97 million in today's currency) in the fall of that year and went public in March 2000, with an initial public offering that generated about another C$6 million.

The company, with 20 employees, reported a first-quarter loss of C$560,251, or C11 cents per share, compared with C$558,170 for the same period last year. At the end of February, the firm said it had C$5.52 million in assets, which included C$3.47 million in cash.

Arius' stock (CDNX:YAR) closed Monday at C$1.50, unchanged.