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(UPDATED: See below.)

800px-antisense_dna_oligonucleotide.jpg“Antisense” drugs that aim to shut down disease-related genes have long been out of favor, and these days live in the shadow of a hotter and newer technologyRNA interference — that does much the same thing. But that hasn’t stopped Encinitas, Calif.-based Excaliard Pharmaceuticals, a newly formed biotech focused on scarring and “fibrotic” conditions, from taking a fresh stab at the field.

The startup just licensed a slew of antisense technology from Isis Pharmaceuticals, and announced that it raised $15.5 million in a first funding round, presumably to help pay for it. Investors in the round included Alta Partners, ProQuest Investments, and RiverVest Venture Partners.

Excaliard is still keeping its head down — its Web site is basically a stub — so it’s not entirely clear exactly which diseases it plans on tackling. Still, it’s notable that the company appears willing to bet fairly heavily on antisense, which Isis and other biotechs have been working on for more than two decades, still without notable success.

Antisense technology essentially involves using short snippets of nucleic acid that bind to “complementary” strands of RNA produced as a gene produces a new protein. That binding effectively shuts down the protein production process, at least in theory. In practice, antisense drugs have failed to live up to their potential, partly because they have had difficulty getting inside cells, which is necessary to get at the RNA involved in protein production. For a graphic version of how this is all supposed to work, click on the image at upper left for a larger version.

Excaliard has paid a fairly substantial amount to get into the antisense field. It handed over an unspecified amount of equity to Isis and made a cash payment of $1 million for the rights to develop antisense drugs against a particular gene — presumably one whose malfunction is related to excessive scarring of some sort. Isis is also entitled to milestone payments and royalties should any drugs make progress.

Although antisense has long gotten a bad rap (multiple high-profile failures will do that), it’s also worth noting that Isis is getting some positive buzz off its leading antisense candidate, an anti-cholesterol drug it now calls mipomersin that has produced some promising results in mid-stage trials. Of course, previous antisense drugs have also looked good in such “phase II” trials, only to collapse in larger and more rigorous tests, but maybe this time will be different.

UPDATE: Actually, there may be a resurgence of sorts underway in antisense. It slipped my mind earlier that the U.K. startup Antisense Pharma just raised the equivalent of $38 million for a late-stage trial of an antisense brain-cancer drug. Also, Isis recently spun out Altair Therapeutics to pursue antisense in respiratory disease.

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