By Mary Welch

Allergan Inc. will pay up to $19 million in a licensing and research agreement with Acadia Pharmaceuticals Inc. to discover, develop and commercialize compounds for glaucoma.

The collaboration is based on Acadia's highly receptor- subtype-selective muscarinic lead compounds.

As part of the agreement, San Diego-based Acadia will transfer to Allergan worldwide rights to products based on two compounds selected by Allergan. In exchange, Acadia could receive up to $19 million for the first development candidate, in the form of up-front fees, research support and milestone payments. Acadia also will receive "substantial" royalties on future product sales worldwide.

"This actually could be a $38 million-plus deal," said Leonard Borrmann, CEO of privately held Acadia. "It they choose a second candidate, there would be similar milestones and royalties."

Acadia, through its internal drug-discovery program, already has identified a "sizable library" of muscarinic compounds that might interest Allergan, Borrmann said. "There is no timetable on this joint venture so we'll continue our research and keep providing Allergan with candidates. But we already have a candidate that we think Allergan will be very interested in."

The compounds are highly selective for a specific subtype of muscarinic receptor. Those receptors initially were identified from Acadia's chemical library using its drug screening and functional genomic analysis platform, Receptor Selection and Amplification Technology (R-SAT).

R-SAT is designed to characterize drug receptor pharmacology, screen target genes against potential ligands, screen receptor genes and characterize orphan receptors, whose biological function or ligand is unknown.

Acadia (formerly Receptor Technologies Inc.) uses R-SAT to identify and validate the molecular targets relevant to a disease and then discover differentiated compounds that specifically regulate these targets. In this case the company will come up with a detailed structure-activity relationship for a family of molecules that selectively targets the subtype of the muscarinic receptor responsible for the lowering of intraocular pressure.

"These molecules also do not interact with other receptor subtypes that cause side effects associated with other glaucoma therapies," Borrmann said.

Although Acadia has other partnerships, including a $69 million deal with Allergan, this is the first collaboration birthed by the company's internal drug-discovery program.

"Our business model has two types of deals," Borrmann said. "The first is a discovery-based deal where we look for clinical compounds for a company. The second is where we discover the compounds from our own internal discovery department and then license them out. This is our first deal in licensing our own compounds."

Acadia's first collaboration with Irvine, Calif.-based Allergan goes back to 1994. In 1997, it was expanded to include identification of drugs centered on five potential targets, including the prostanoid and alpha adrenergic receptors, both of which are involved in glaucoma. Allergan agreed to pay $6 million up front (buying a 12.5 percent ownership in Acadia), three years of research support and milestones of up to $12.5 million for the first product developed for each of five receptor targets. At the time of the 1997 deal, Borrmann was vice president of business development for Allergan and helped negotiate the deal. (See BioWorld Today, Sept. 26, 1997, p. 1.)

Since the start of that collaboration, Acadia identified a subtype-selective alpha-adrenergic agonist for glaucoma. Alpha-adrenergic agents lower intracular pressure, partly by decreasing inflow of ocular fluid. Acadia's new receptor-selective muscarinic lead compounds are designed to increase the outflow of fluid from the eye.

"There are a variety of different medications for glaucoma," Borrmann said. "In fact about two-thirds of all patients take more than one medication. The alpha-adrenergic and the receptor-selective muscarinic compounds are complementary with two different mechanisms. In fact, we believe both could become front-line therapies and maybe used as adjuncts with each other."