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GSK and Isis in Antisense Deal

Is antisense making a comeback? Isis Pharmaceuticals this morning announced a deal with GlaxoSmithKline worth up to $1.5 billion to develop drugs to treat rare and infectious diseases.

Here’s how the math breaks down: Isis gets $35 million upfront, and on average $20 million for every program it brings into Phase II trials. At that point, GSK can exercise an option to license the compound and take on all the further development costs. If GSK opts in on and commercializes  all six drugs covered by the deal, Isis ends up with $1.5 billion, and also gets the usual double-digit royalties on sales.

Technically, a range of technologies fall under the umbrella of “antisense,” which describes technology that targets the RNA controlling the production of proteins. That broad term encompasses RNAi, microRNA, and Isis uses oligonucleotides, or a string of nucleic acids, to intercept messenger RNA.

But while RNAi-based drugs have been the darling of investors in recent years, antisense has had a bit more of a rollercoaster ride. The colossal failure of Genta’s antisense drug Genasense (not to mention all the money Aventis spent on it) did not help the technology’s cause. Isis has stuck with it, though, and for good reason: the biotech has a lock on the intellectual property around antisense, and now owns a piece of pretty much any antisense drug in development. Further, by tweaking the chemistry of its oligonucleotides, Isis managed to significantly improved delivery of the genetic bits, a problem siRNA has yet to overcome.

Still, safety questions linger. Isis and Genzyme, which signed a major deal with Isis in 2008 to co-develop the cholesterol drug mipomersen, have seen investor hopes for a multi-billion dollar drug fade as the drug caused liver enzyme levels to be raised. Perhaps the deal with GSK suggests some confidence that the off-target effects of antisense can be tackled.

Update: Needham & Co’s Mark Monane was upbeat on the deal.  ”We believe this collaboration represents another example of the value of Isis’ core technology for the potential treatment of hard-to-treat illnesses.” he said this morning ina note to investors. “Furthermore, the agreement allows Isis to utilize its skills in early stage development, and GSK to use its skills in later stage development.”

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  • [...] GSK and Isis in Antisense Deal | The Haystack [...]

  • [...] unlike RNA interference (RNAi) technology, which uses double-stranded oligos. As we’ve written, antisense drugs have been on something of a roller-coaster ride, being highly touted in the [...]

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