By Debbie Strickland

In a $75 million deal, privately held ICAgen Inc. has granted to Bristol-Myers Squibb Co. (BMS) worldwide rights to ion channel inhibitors designed to prevent and treat atrial fibrillation, the most common type of heart arrhythmia.

Currently marketed treatments for atrial fibrillation cause a wide variety of side effects, including, in some instances, other arrhythmias. Taking a different approach, ICAgen's compounds act on an ion channel that so far has been found only in the atria of the heart.

"We think these are likely to be the safest compounds for atrial fibrillation available, not to mention very effective," said Douglas Richards, BMS' associate director of biotechnology licensing.

"Not only does ICAgen bring several chemical classes of interesting compounds," Richards added, "but a huge amount of expertise in ion channels as well."

BMS, of New York, does not have an atrial fibrillation product, but markets an array of cardiovascular drugs, including Pravachol, a lipid-lowering medication.

Under terms of their deal — a two-year agreement with an option to extend for a third year — BMS will provide an up-front payment, research funding and milestones totaling more than $75 million. ICAgen also will receive royalties on any marketed drugs that result from the collaboration. Both companies will perform preclinical research, and BMS will run the clinical trials. Investigational new drug applications could come as early as 1998.

"We've positioned ourselves so that we can move into the clinic with more than one product, and it is a possibility that we could [enter the clinic] in 1998 or 1999," said P. Kay Wagoner, ICAgen's president and chief executive officer. "Certainly it is our intent to aggressively move things along, but, of course, these things have to mature."

Currently at 25 employees, ICAgen, of Research Triangle Park, N.C., will not "require a major expansion" to pursue the collaboration, she said.

Representatives of both companies said the program eventually could yield multiple promising compounds to still atrial fibrillation, a condition that is more than just a heart flutter.

Atrial fibrillation is associated with an increased risk of embolism, stroke, heart failure and early death. In the U.S., more than 2.5 million people are affected, and each year it brings 160,000 new cases. The annual estimated cost of the disease in the U.S. is more than $1 billion.

ICAgen Focusing On Ion Channels

ICAgen officials said they believe theirs is the first company to work exclusively on discovery and development of drugs that modulate the flow of molecules through ion channels.

Founded in 1992 as a virtual company, ICAgen has been actively pursuing research and development since 1995 and has raised $11 million in financing.

The company has two other corporate collaborations, one of them with Indianapolis-based Eli Lilly and Co., providing ICAgen exclusive access to Lilly's combinatorial small molecule compound libraries for screening against potassium, chloride and water channel targets. The other agreement, with ArQule Inc., of Medford, Mass., is a joint venture to screen ArQule's combinatorial libraries.

Wagoner emphasized, however, that ICAgen is not just a screening company.

"We do everything, from picking the targets to cloning targets to producing the compounds to optimizing them and taking them into appropriate in vitro and in vivo studies," she said.

A key feature of ICAgen's drug discovery methodology is parallel processing — testing multiple molecules on many targets simultaneously, in order to obtain evidence of potency and selectivity.

ICAgen — whose name contains an acronym for Ion Channel Advances" — can discover ion channel molecules and take them from concept to lead optimization in less than six months, company officials said. About 10 new leads are discovered each month, with six "quality leads" moving into development each year.

ICAgen is working in seven therapeutic areas: Parkinson's disease, memory loss, epilepsy, transplantation rejection, arrhythmias, Reynaud's disease and gastrointestinal motility disorders.

Looking toward the future, ICAgen will be seeking additional collaborators and, if all goes well, may file for an initial public offering.

Taking the company's technology public, said Wagoner, "certainly will be in our future, but as to when, that depends on reaching our milestones." *