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Santaris Plans Phase II Trial of miRNA-Targeting HCV Drug

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By Doug Macron

BOSTON — Santaris Pharma is close to completing a second phase I study of its microRNA-targeting hepatitis C therapy SPC 3649, and expects to move the drug into phase II development later this year, a company official told RNAi News.

The official, CSO Henrik Orum, also said Santaris has dropped its near-term plan to seek a partner for the therapy, which it will instead carry on its own at least through the first phase II trial in HCV-infected patients

SPC3649 targets miR-122, the most abundantly expressed miRNA in the liver and one linked to cholesterol regulation and lipid metabolism. It is based on Santaris' locked nucleic acid technology, which comprises nucleic acid analogs in which the ribose ring is locked by a methylene bridge connecting the 2'-O atom with the 4'-O atom.

In mid-2008, Santaris moved the drug into a phase I study, making it the first to test a miRNA-targeting drug in man. According to Orum, that single ascending dose trial enrolled 64 healthy volunteers and initially examined doses of the drug up to 6.4 mg/kg.

"With the initial top dose of 6.4 [mg/kg], we didn't see anything in terms of the safety issues," he said. As such, the company amended the trial to include 9 and 12 mg/kg doses.

In addition to observing no significant adverse events associated with SPC3649, Santaris saw evidence of a pharmacological effect as measured by reductions in serum cholesterol — a biomarker for miR-122, Orum explained this week during a presentation at the IBC Life Sciences' Oligonucleotide Therapeutics Discovery conference held here.

The company also initiated a second phase I study, this time examining multiple ascending doses of the drug, which it expects to wrap up shortly, he said.

Because data from this trial have not been publicly disclosed, Orum declined to comment on them. He did say, however, that Santaris is "happy with the results" and that the company is slated to begin a phase II study in HCV-infected patients "later this year."

Both phase I studies were conducted in Denmark. He noted that the company is considering in which countries it will run the phase II trial.

Meanwhile, Santaris has made the decision to keep SPC3649 in-house after partner GlaxoSmithKline opted against licensing the drug.

In late 2007, the companies inked a deal to develop and commercialize antiviral drugs based on the LNA technology (RNAi News 12/20/2007). As part of that arrangement, GlaxoSmithKline had the option to in-license SPC3649.

But as reported by RNAi News, GlaxoSmithKline let that option expire (RNAi News 12/3/2009), leaving Santaris free to host licensing negotiations with other interested parties.

Notably, GlaxoSmithKline later said it had partnered with rival miRNA drug firm Regulus Therapeutics on a miR-122-targeting drug for indications including HCV (RNAi News 2/25/2010).

This week, however, Orum said that despite "considerable interest … [in SPC3649] we've elected to keep it as a Santaris asset until we have conducted the first trials in patients with HCV. We think there is significant value creation in that phase, and we'd obviously like to retain that within Santaris … we have patient data."

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