DUBLIN, Ireland ¿ Elan Corp. plc and Isis Phar maceuticals Inc. have agreed to form a joint venture to develop a platform technology for oral delivery of antisense drugs. Dublin-based Elan is underpinning the deal with a US$27 million investment in Isis, of Carlsbad, Calif., consisting of US$15 million of common stock purchased at a premium to market, and US$12 million of convertible exchangeable preferred stock.

The joint venture will be established as a subsidiary of Isis, which will hold 80 percent of its stock initially. Elan has an option either to increase its stake to 50 percent or to increase its shareholding in Isis.

Isis¿s antisense inhibitor of tumor necrosis factor-alpha (TNF-a), a gene implicated in a range of inflammatory conditions, is the first drug slated for development by the new venture. Mike Sember, executive vice president for business development at Elan, said no other candidates have been selected yet. The agreement is ¿wide open,¿ he added, and the partners have not fixed the total number of compounds they will develop together.

The inclusion of other candidates will depend on progress in developing the oral formulation of the antisense TNF-a inhibitor. Sember said clinical trials are about 33 months away. However, the partners will work on an intravenous formulation of the drug in parallel, and Sember expects this to reach the clinic in a year.

Antisense drugs have been a long time delivering on their initial promise. Isis¿s marketing partner, Ciba Vision, the eye care division of Basel-based Novartis AG, launched the first, Vitravene (fomivirsen), for treatment of cytomegalovirus-induced retinitis in AIDS patients, last November. That launch, said Sember, ¿convinces us that the technology is real.¿

Vitravene is applied topically, however. The precise strategy behind the Elan and Isis plan to deliver antisense drugs orally is not yet in the public domain. Mary Martin, vice president of strategic research-and-development planning for Elan Pharmaceutical Technologies, the company¿s drug delivery arm, declined to reveal technical details in advance of a kick-off meeting planned for next month.

Elan and Isis have generated in-house data which indicate that oral delivery of antisense drugs is ¿feasible,¿ she said. Elan has previously demonstrated successful oral delivery of other high-molecular-weight, charged compounds, such as proteins and peptides.

The challenge associated with delivering antisense RNA across the gut barrier is similar, she said. Elan has been busy, of late, with four other deals announced this month. It has formed a joint venture with combinatorial chemistry firm Multiple Peptide Systems, of San Diego, for the development of both oral and non-oral drug delivery technologies. Elan also invested US$5 million in the company, in a separate transaction.

It has invested close to US$3 million to fund the development of a glucose monitor with Bioject Medical Technologies Inc., of Portland, Ore., and established a joint venture with Celtrix Pharmaceuticals Inc., of San Jose, Calif., based on the development of SomatoKine for osteoporosis treatment using Elan¿s Medipad delivery system. The deal involves an initial investment on the part of Elan of up to US$12.8 million in Celtrix preferred stock, plus an additional $2.5 million of Celtrix common stock.

Elan has also resolved a legal dispute with Fuisz Technologies Ltd., of Chantilly, Va., and has signed a license and manufacturing agreement with the company. Elan has purchased close to five percent of Fuisz¿s equity and will nominate a member of the company¿s board.

The company¿s stock (NYSE:ELN) plunged 20 percent, to US$60 last week on news that its new drug application submission for Ziconotide, an N-type neuronal calcium channel blocker for treatment of chronic neuropathic and malignant pain, will be delayed until the end of the year. Last December, Elan said it expected to file in the first quarter this year. Last week, the company said the delay ¿should have little effect on the timing of the product¿s eventual market availability.¿ n