Biogen Idec (NASDAQ:BIIB) is going back to the antisense well, teaming up with Isis Pharmaceuticals (NASDAQ:IONS) for the fourth time in two years.

Endorsements of a technology don't get bigger than that.

For the latest deal, Biogen is giving Isis $100 million up front, and Isis is eligible to receive as much as $220 million per drug developed through the new collaboration. Isis would also collect royalties on the drugs if they make it to the market.

Unlike the earlier collaborations on spinal muscular atrophy, myotonic dystrophy type 1, and a third that covered three novel targets for neurological disorders, this partnership is an earlier development-stage deal.

The companies will start with basic research to identify new targets for different neurological disorders; on the conference call, Isis and Biogen cited amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, as one of the potential diseases.

Isis and Biogen think they can identify two or more targets a year. Not all of them are going to work out, but even one drug a year would be a pretty impressive partnership.

Molecular switch
The attraction of Isis' antisense technology lies in its simplicity. Antisense works by inhibiting the production of a specific protein. Essentially it can turn a specific gene off by acting on the RNA molecule that is the intermediary between the gene and the protein it encodes for.

All you need to do is find a protein that improves disease symptoms when its expression is knocked down. Designing an antisense molecule to bind to the RNA is typically much easier than creating a drug that can inhibit the protein's function.

Isis isn't the only one using this approach. Alnylam Pharmaceuticals (NASDAQ:ALNY) has a related technology called RNAi that acts on the RNA intermediary, degrading it through another mechanism. Biogen has a partnership with Alnylam as well, so it clearly likes the strategy.

But Isis is the leader in the field, mostly because it's been doing it for so long; Isis was founded in 1988!

While the idea of antisense is simple, the development of the technology has been challenging, mostly because the drugs weren't particularly stable. Fortunately, Isis seems to have solved the problem with next-generation technology, highlighted by its recently approved drug Kynamro.

Best drug for the job
Admittedly, there are other ways to treat diseases other than lowering protein expression; small molecules and antibodies can inhibit the protein's function by binding to it. Interestingly the Biogen-Isis partnership allows for the companies to determine the best way to target the proteins they discover. If an approach other than antisense is most feasible, Biogen will take over development and Isis will get a smaller royalty for its early discovery effort on that drug.