By Matthew Willett

BioChem Pharma Inc. will collaborate with Adherex Technologies Inc. for the development and marketing of a family of anti-angiogenic cancer therapeutics designed to starve tumors by inhibiting blood vessel adhesion.

Ottawa-based Adherex could receive up to $25.5 million from milestone payments and an equity investment, in addition to a portion of sales revenues.

Adherex's Exherin, a proprietary anti-angiogenic compound, will be developed both alone and in conjunction with chemotherapeutic agents.

BioChem Chief Scientific Officer Gervais Dionne said Adherex technology complements BioChem's pipeline of novel therapeutics. That prompted this collaboration, he said, as well as expands BioChem's oncological pipeline.

BioChem, of Laval, Quebec, also is developing two anticancer compounds, a pain control compound and five vaccines in addition to Fluviral S/F, already marketed by the company in Canada.

BioChem's franchise product, lamivudine, is on the market in under different names and combinations for HIV and hepatitis. It also markets Pacis, an immunotherapeutic BCG for bladder cancer.

"Adherex is a young and dynamic company which has developed this technology platform to treat cancer, and I think there is a complementariness and a synergy about them," Dionne said. "What we can do with them and their program in this subject is develop it faster. The initial goal is to demonstrate proof of the overall concept in preclinical trials."

Adherex technology takes advantage of vascular adhesion inhibitors, compounds that stop cells on vascular surfaces from connecting to each other, cementing tumor vasculature.

In the past, anti-angiogenic compounds have focused largely on inhibiting further vascular development in tumors. The Adherex technology, Dionne said, shows promise for attacking both existing vasculature and inhibiting new vasculature formation.

"There are certain molecules which are on the surface of cells which keep cells bound together, cell adhesion molecules," Dionne said. "This technology targets this family of cells and molecules called cadherins. This group is identified as the binding sites where cadherins bind together and stick together. The approach has been to discover a small molecule which will disrupt cell adhesion."

The caveat, he said, is to protect existing vasculature unassociated with tumor growth.

"The tumor vasculature is much less bound together; the blood vessel is much weaker because the vasulature is bombarded by different proteins and some other mechanisms. It's a vasculature that's leaky, so it's much easier to disrupt," Dionne said.

If that can be done, he added, it could loosen tumor structure, opening the tumor to chemotherapeutics and speeding the process of tumor disruption significantly. Dionne said it's too early to tell how much more quickly tumors could be killed if the collaborative anti-angiogenic compounds show efficacy.

And combining the anti-angiogenic therapy with an existing BCP DNA chain terminator/polymerase inhibitor compound could provide even further therapeutic benefit.

"It's a complement to a product we have in our pipeline, Troxatyl, which is a novel chemotherapeutic approach which uses a DNA chain terminator for cytotoxis. We believe the two agents, used in combination, if they attack the tumor directly and at the same time, will destroy the blood supply and may destroy the tumor more efficiently and more rapidly," Dionne said.

Troxatyl (troxacitabine) is undergoing a Phase II trial for safety and efficacy begun in March 1999.

BioChem Pharma's stock (NASDAQ:BCHE) fell.18.75 cents Tuesday to close at $21.437.

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