By Randall Osborne

To boost its discovery and development of therapeutic modulators of G protein-coupled receptors (GPCRs), Arena Pharmaceuticals Inc. raised $17 million in a private offering.

San Diego-based Arena had intended to raise $10 million in the placement, which included an equity investment by Tripos Inc., of St. Louis, with which privately held Arena has been collaborating since July 1997.

"There's lots of money out there for good [technology]," said Jack Lief, president and CEO of Arena.

Whereas the usual mode of drug discovery uses assays for compounds that block the binding action of the natural ligand to its receptor, Arena's constituitively activated receptor technology (CART), which measures receptor activity, lets the company screen "orphan receptors" - that is, those for which the natural ligand is not known.

"We do a primary efficacy screen," Lief said. "If you just measure ligand displacement, that doesn't mean you're doing anything to the receptor. We measure receptor activity directly."

Conventional discovery requires identifying the receptor and its ligand before screening. But finding the ligand can take years, and Arena's method speeds the process considerably by working with orphan receptors, hundreds of which have been identified in the ongoing work of the Human Genome Project.

The time from gene discovery to clinical studies of a drug, which can take 10 years, "could take a year and a half with CART," Lief told BioWorld Today. "You know already [with CART] that the drug is effective at the receptor - it's not just displacing ligands - so you're that much farther along. You can screen for agonists as well as antagonists, and agonists are very tough to screen for."

Arena, founded in April 1997, said last year it had chosen five orphan receptors for which development and drug screening are under way: AP123 (involved in cerebral blood flow, with potential applications in stroke and epilepsy); AP-20 (hypothalmic circuits, for drugs against obesity and diabetes); AP-14 (hippocampal circuits, for Alzheimer's disease treatments); AP-31 (for estrogen receptor regulation, with potential application in breast cancer); and AP-40 (implicated in cell growth, for development of drugs against various cancers).

Arena also has in-licensed drug candidates for preclinical studies. Of these, T-82, a patented acetylcholine enhancer, is the farthest along, with a lead compound for Alzheimer's disease in Phase I trials.

Lief said the company has more than 100 orphan receptors "in various stages, and we'll have several hundred by the end of the year."

Patents Pending On Three Lead Series Of Molecules

In the deal with Tripos, Arena provides its receptor-identification technology, screening, and biology capabilities. Tripos provides informatics, access to its LeadQuest compound libraries, computational analysis and design, and medicinal chemistry for lead optimization.

Aiming at therapeutic targets and lead compounds, the two companies will jointly pursue pharmaceutical partners. So far, they have identified three lead series of molecules and filed for patents on them.

Placement agent for Arena's offering was ING Baring Furman Selz LLC, of New York. Co-lead investors were MPM Asset Management LLC, of Cambridge, Mass., and International Biomedicine Management Partners Inc., of Basel, Switzerland.

Other investors were Tripos; OrbiMed Advisors LLC, of New York; and A.M. Pappas & Associates, of Durham, N.C.