By Lisa Seachrist

Washington Editor

Antisense specialist Isis Pharmaceuticals Inc. and Irish drug-delivery giant Elan Corp. plc joined forces to develop oral antisense therapies for a variety of diseases.

Dublin-based Elan will make a $27 million equity investment in Carlsbad, Calif.-based Isis to form a new subsidiary of Isis dedicated to developing oral formulations of antisense drugs. The first drug to be developed by the subsidiary will be an antisense inhibitor of tumor necrosis factor-alpha (TNF-a), which is a factor in a number of inflammatory diseases, such as rheumatoid arthritis.

¿We were delighted, to say the least, with the collaboration with Elan,¿ said Jane Green, senior director of investor relations at Isis. ¿This deal is really coming at just the right time in the development of this technology.¿

Under the terms of the agreement, Elan will buy $15 million worth of Isis stock at a 40 percent premium to market prices. Elan will also purchase $12 million of convertible exchangeable preferred stock. Elan has the right to convert the preferred stock into either an ownership interest in the yet-to-be-named subsidiary or in Isis itself.

At the outset Isis will be the majority shareholder of the subsidiary, owning 80 percent. The collaboration will be financed with Elan¿s equity investment as well as a line of credit that Elan is making available to Isis. The first goal of the joint effort will be to develop a technology platform that creates bioavailable antisense drugs.

¿We¿ve made significant progress toward that goal,¿ Green said. ¿The collaboration with Elan is going to accelerate the headway that we have already made.¿

Isis has one approved antisense drug ¿ Vitravene for the treatment of CMV-induced retinitis in AIDS patients, which is given as an intraocular injection. Despite a product approval, many have remained skeptical about the future of the antisense drugs because the drugs haven¿t been able to be formulated as a tablet or capsule.

Devising a technology that would create oral formulations of the drug could unleash the potential of antisense technology, which uses small strings of nucleotides to bind to messenger RNA and prevent a cell from producing specific proteins. The technology offers a very specific way to turn off the expression of certain genes in a cell.

First Drug Candidate Now In Preclinicals

Isis currently has six antisense compounds in clinical trials for the treatment of diseases ranging from Crohn¿s disease to cancer to asthma. The company¿s Crohn¿s disease drug, an inhibitor of ICAM-1, is currently in a pivotal trial. All the drugs are given as infusions.

¿Creating a bioavailable form really is the final technological hurdle for antisense,¿ Green said. ¿That is why we are very excited about the potential of this collaboration.¿

The collaboration¿s first drug candidate, an inhibitor of TNF-alpha, is still in the preclinical development stage.

Isis stock (NASDAQ:ISIP) closed at $9.875 per share Tuesday, down 6.25cents. Elan¿s stock (NYSE:ELN) closed at $70.06 a share, down $4.812.