By Debbie Strickland

San Diego-based Axiom Biotechnologies Inc. has lined up its third — and potentially most lucrative — corporate collaboration, joining forces with two Japanese firms to hunt small-molecule cancer drugs directed at an undisclosed apoptosis-associated target.

Axiom will use the target — licensed by fellow start-up Zaiya Inc., of Kyoto — to develop cell-based and biochemical assays for use with Axiom's partially completed High Throughput Pharmacology System (HT-PS), which provides functional profiling of hits. Axiom will follow up with in-house optimization of leads.

Zaiya and established pharmaceutical house Nippon Kayaku Co. Ltd., of Tokyo, have committed research funding. Axiom may also receive other, success-contingent payments. In return, Nippon Kayaku gains Asian marketing and manufacturing rights to products from the collaboration, plus options for other territories outside of North America.

Zaiya and Axiom, which have been collaborative partners since September 1996, are jointly seeking a North American development and marketing partner for therapeutics resulting from this project.

Axiom will receive "multimillion-dollar" research funding for three years, plus license fees, milestones and "double-digit" royalties, Jim Linton, senior director of business development, told BioWorld Today. Additional terms were not disclosed.

Axiom's HT-PS system of pharmacology characterization is designed to profile tens of thousands of compounds per week for hit activity, potency, target specificity and cytotoxicity.

The first module of HT-PS, and the most time-consuming to design, is already online to handle the first three of those tasks — activity, potency and specificity profiling.

"We have two more phases to go, and it's coming very quickly," said Linton, though he would not reveal the company's timeline, except to say that Axiom was beating it.

The platform consists of instrumentation; natural, cell-based assays and assay protocols; laboratory information management tools; and pharmacoinformatic analytical tools.

"This high-throughput platform is going to be very important for addressing the emerging bottleneck in the drug discovery process," said Linton. "We should all expect to be generating tens of thousands of hit molecules per week within the next several years. In order to move these compounds through without creating a backlog of hits, we have to have a high-throughput system for evaluating pharmacological activity."

Although the apoptosis project will be conducted at Axiom's facilities, the company's business model calls for technology transfers to partners of customized versions of the high-throughput platform, plus the development of tailored assays for each partner's targets.

"Our goal is to develop this platform and engraft it into partners' facilities so they can perform rapid discovery from a pharmacological perspective while maintaining possession of their compounds," Linton said.

Cadus Pharmaceutical Corp., of Tarrytown, N.Y., will be at the head of the line for the system, having earlier this year agreed to an equity investment of up to $4 million — representing as much as 38 percent of Axiom on an as-converted basis. Cadus invested $2 million up front and committed to an additional $2 million upon receipt and acceptance of HT-PS within an undisclosed time period.

Axiom also has a separate collaborative agreement with Zaiya covering the identification of small-molecule therapeutics for allergies, asthma and inflammation.

The research focuses on CD40, a B cell surface receptor, which activates intracellular signaling proteins that cause B cells to produce immunoglobulin E (IgE). Elevated levels of IgE in the blood have been linked to asthma, allergies and other inflammatory diseases.

Axiom will attempt to develop small-molecule compounds that enter B cells and block the signaling proteins, preventing IgE production.

Founded in 1995, Axiom commenced operations in the spring of 1996. The privately held company has 21 employees and 7,500 square feet of laboratory space. *

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