By Randall Osborne
With $7.5 million in new private financing for its antigen identification program, Argonex Inc. is shopping for collaborators to develop immunotherapeutic vaccines against a variety of cancers.
"We're going to license them out, but we want to be partners in developing the technology," said Ian Ratcliffe, chief financial officer and chief operating officer of Charlottesville, Va.-based Argonex.
Founded in 1994, the company uses mass spectrometry with immunology, in a technology called Direct Identification of Relevant Epitopes for Clinical Therapeutics (DIRECT). The system, invented by two researchers at the University of Virginia (UVA), also in Charlottesville, zeroes in on antigens that specifically trigger T cell responses against diseased cells.
Using established tumor cells and cytotoxic T cell lines, Argonex extracts and analyzes potential peptide antigens bound to class I major histocompatibility complex molecules. These are assayed for antigenic activity through a "simultaneous" (split) mass spectrometry experiment, and candidate antigens are sequenced using tandem mass spectrometry. They are synthesized and tested with the biological assay.
So far, DIRECT has identified nine tumor-associated antigens.
Once identified, the "functional antigens" may be applied with a broad range of vaccine delivery systems — with a potentially broad range of collaborators. Ratcliffe cited several likely partners.
"SmithKline [Beecham plc, of London] clearly has delivery capability, and a low share of the [cancer] therapeutic market, only about 1 percent of existing sales in oncology drugs," he said.
"Bristol-Myers [Squibb Co., of New York] is number one, with 34 percent of cancer products, and Zeneca [Group plc, of London] has 27 percent," he added. But the field of cancer vaccines is "so new that there's no obvious [corporate] partner right now," Ratcliffe said.
UVA is collaborating with Argonex on melanoma and squamous cell lung, head and neck cancers. In ovarian cancer, partners are the University of Pittsburgh Cancer Institute (UPCI), in Pittsburgh, and M.D. Anderson Cancer Center, in Houston.
Partners with Argonex in colorectal cancer are UVA, UPCI and The Wistar Institute, in Philadelphia. For prostate cancer, the collaborator is Northwest Biotherapeutics, of Seattle.
Until more corporate partners climb aboard, Argonex is moving ahead on its own, conducting Phase I/II trials with a melanoma vaccine in late-stage patients. The vaccine is based on four antigens derived from the gp100 and tyrosinase proteins.
"We've identified as many melanoma antigens as we feel we need to identify," Ratcliffe said. "They're our proof of principle, really. We're going after that disease because we can."
Clinical data are expected in about 18 months.
Finding antigens that generate specific immune responses has been the main hurdle for companies trying to develop immunotherapeutic vaccines as complements to existing treatment regimens.
Next, the company plans to focus on lung, ovarian, colorectal and prostate cancers. Argonex has identified one lung-cancer antigen and a patent application for it has been filed.
Argonex has an unrelated collaboration with Dyax Corp., of Cambridge, Mass., to discover and develop affinity ligands and separations tools to improve urokinase purification processes.
Urokinase, a naturally occurring enzyme with thrombolytic activity, is commonly used for catheter clearance. It is marketed in Europe for treatment of vascular blockade associated with myocardial infarction and other cardiovascular disorders. In May, the two companies signed a continuation of the partnership, initiated in 1995.
"It's not the core of our business, but it's been successful," Ratcliffe said. Argonex also is exploring new analytical applications for its mass spectrometry, he added.
Half of Argonex's research efforts are supported with revenues from Upstate Biotechnology Inc., of Lake Placid, N.Y., owned and operated by Argonex. Upstate supplies cell signaling reagents for biomedical research. The two companies employ about 100, and about 70 of those work for Upstate.
The lead investor in the $7.5 million financing was Healthcare Ventures LLC, of Cambridge, Mass. *